UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: 12-MAR-2014 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUfiON PREVENTION 

SUBJECT: Imazethapyr. Human Health Assessment Scoping Document in Support of 

Registration Review. 

PC Code: 128922, 128923 

Decision No.: 483346 

Petition No.: N/A 

DP ~arcode: 04 15244 

Registration No.: N/A 

Regulatory Action: Registration Review Scoping Document 

Risk Assessment Type: N/A Case No.: 7208 

TXRNo.: N/A - CAS No.: 81335-7~ 101917-66-2 

MRID No.: N/A 40 CFR: § 180.447 

FROM: 

Ch

Kelly 

este

M

r E

. Lowe,_Env

. Rodnguez, 

ironm

Ph.D.

entm 

, Pharm

Scie tist_~~

co t ·· , 

~ 

William D. Wassell, Chemist • 

Risk Assessme ' nt Branch l (RAB 1) 

Health Effects Division (HED, 7509P) 

THROUGH: Charles W. Smith III, Branch Chi""'--_ 

George F. Kramer, Ph.D., Senior Chemi ~~~~2!~._,~:...--­

RAB 1/HED (7509P) 

TO: Katherine St. Clair, Chemical Review Manager 

Pesticide Re-Evaluation Division (PRD) (7508P) 

Attached is HED's seeping document for imazethapyr to support Registration Review. 

Page 1 of 18 
____ Imaze!hapyr Registrati?~~eview Human Health Ass~~sment Scopin~ Document 

Executive Summary 

HED has prepared a seeping document to support Registration Review of imazethapyr. 

Imazethapyr [ ( ± )-2-[ 4,5-dihydro-4-methyl-4-( 1-methylethyl)-5-oxo-1 H-imidazol-2-yl]-5-ethyl3-pyridinecarboxylic acid] is a member of the imidazolinone class of chemicals that kills weeds 

by inhibiting the enzyme acetohydroxyacid synthase (AHAS). This enzyme is involved in the 

synthesis of three branched-chain aliphatic amino acids. The inhibition causes a disruption in 

protein synthesis that leads to an interference in DNA synthesis and cell growth. 

lmazethapyr, as its acid or ammonium salt, is registered for use on legume vegetables (Group 6), 

nongrass animal feeds (Group 18), soybean, peanut, rice, and field corn. In addition, there is a 

tolerance for imazethapyr on imported canola. It is also registered for use on turf, including 

highway rights of way, athletic fields, parks, residential lawns, sod farms, golf courses, and areas 

around schools/universities, libraries, hospitals, and commercial/industrial areas. In addition, 

there is a Special Local Needs (SLN) Registration for imazethapyr (SD 12000 l; provides 

additional environmental precautions and soil type restrictions) and one SLN for imazethapyr, 

ammonium salt (AR130002; for use on edamame). The most recent human health risk 

assessment was performed in 2005 and was for an increased tolerance on rice and crayfish 

(Memo, H. Johnson et al., 11-NOV-2005; D321723). There are currently no pending PRIA 

actions for imazethapyr. 

HED has evaluated the status of the human health assessments for imazethapyr to determine 

whether sufficient data are available and whether any updates are needed to support Registration 

Review. HED has considered all available data and human health risk assessments for 

imazethapyr with respect to its toxicity, exposure, and usage databases, and the most updated 

Agency science policy and risk assessment methodologies to support Registration Review. 

The toxicity database is adequate for hazard characterization and Food Quality Protection Act 

(FQPA) Safety Factor (SF) evaluation. Imazethapyr exhibits low toxicity in mammalian 

systems. In previous risk assessments, toxicity points of departure were based on NOAELs from 

studies where no effects were observed at the limit dose or effects were observed at excessively 

high dose levels (~1 000 mg/kg/day) not relevant for human health risk assessment. Thru 

Registration Review, it has been determined that these points of departure are no longer 

appropriate and no toxicological points of departure will be selected for imazethapyr for 

Registration Review and future actions, and an additional safety factor to protect children is not 

needed. As a result, a quantitative risk assessment is not required for imazethapyr for 

Registration Review to support the currently registered uses. 

The residue chemistry and dietary-exposure databases for imazethapyr are adequate to support 

current registration requirements. 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. 

There is sufficient information available to assess occupational and residential exposure and risk 

from the registered uses. The most recent occupational and residential exposure assessment was 

Page2 of 18 
Imazethapyr Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 3 of 18

performed for the November 2005 human health risk assessment and no risk estimates of 

concern were identified. Residential exposure scenarios have not previously been assessed. 

However, since it has been determined that a qualitative assessment is sufficient based on the 

low toxicity of imazethapyr, quantitative occupational and residential exposure assessments are

not needed for Registration Review for HED to conclude with reasonable certainty that nondietary exposures to imazethapyr do not pose a significant human health risk.

Based on the low frequency and generally low severity of incident cases reported for 

imazethapyr in both IDS and SENSOR-Pesticides, there does not appear to be a concern at this 

time that would warrant further investigation. The Agency will continue to monitor the incident 

information and if a concern is triggered additional analysis will be conducted during

Registration Review. It was noted that in one Agricultural Health Study (AHS) study, authors 

observed an elevated risk of bladder and colon cancers in relation to imazethapyr use; however, 

EPA notes that the structure of imazethapyr is unlike the classic structures of the carcinogenic 

aromatic amines and that the toxicological studies submitted to EPA for registration of 

imazethapyr do not show any evidence of carcinogenicity. The Agency will continue to monitor 

the literature for further investigations relating to potential elevated risk of bladder and colon 

cancers in relation to imazethapyr use.

There are no data deficiencies for imazethapyr. Since it has been determined that no 

toxicological points of departure will be selected for imazethapyr for Registration Review and 

future actions, the Agency does not anticipate the need for conducting any quantitative exposure 

or risk assessments during Registration Review.

1.0 Introduction

Imazethapyr is a member of the imidazolinone class of chemicals that kills weeds by inhibiting 

the enzyme AHAS. This enzyme is involved in the synthesis of three branched-chain aliphatic 

amino acids. The inhibition causes a disruption in protein synthesis that leads to an interference 

in DNA synthesis and cell growth. Imazethapyr, as its acid or ammonium salt, is registered for 

use on legume vegetables (Group 6), nongrass animal feeds (Group 18), soybean, peanut, rice, 

and field corn. There is a tolerance for imazethapyr on imported canola. It is registered for use 

on turf, including highway rights of way, athletic fields, parks, residential lawns, sod farms, golf 

courses, and areas around schools/universities, libraries, hospitals, and commercial/industrial 

areas. In addition, there is a SLN Registration for imazethapyr (SD120001; provides additional 

environmental precautions and soil type restrictions) and one SLN for imazethapyr, ammonium 

salt (AR130002; for use on edamame). The most recent human health risk assessment was 

performed in 2005 and was for an increased tolerance on rice and crayfish (Memo, H. Johnson et 

al., 11-NOV-2005; D321723). There are currently no pending PRIA actions for imazethapyr. 

The structure, chemical names, and other identifiers as well as the physical/chemical properties 

of imazethapyr can be found in Attachment 1.

2.0 Hazard Characterization/Assessment

The pesticidal mode of action of imazethapyr involves inhibition of the enzyme AHAS which is 

a key plant enzyme in the biosynthesis of the amino acids leucine, isoleucine, and valine. 

Mammals seem to lack this biosynthetic pathway and must obtain these amino acids from their 

diet. The low toxicity exhibited by imazethapyr is consistent with the proposed pesticidal mode 

of action and the lack thereof in mammalian systems.
Imazethapyr Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 4 of 18

Toxicological Studies Available for Analysis

In the November 2005 risk assessment for imazethapyr, no additional toxicity data were deemed 

required because of the low toxicity exhibited by imazethapyr and structurally similar 

compounds (imazamox, imazapic, and imazapyr). The Hazard and Science Policy Council 

(HASPOC) met (TXR# 0056841, 12/17/13) to evaluate the need for inhalation, immunotoxicity, 

and neurotoxicity (acute and subchronic) studies. The HASPOC concluded that these studies are 

not required at this time. Therefore, the current toxicity database is adequate for hazard 

characterization, toxicity endpoint selection, and FQPA SF evaluation.

Absorption, Distribution, Metabolism, and Excretion

Following oral administration in rats, radiolabeled imazethapyr was extensively absorbed as 

reflected by the high percentage of the radioactivity recovered in urine (89-95% in the urine and 

6-11% in the feces). Metabolism of the parent chemical was minimal as the major residue 

excreted in both urine and feces was the parent chemical. There was no evidence of 

bioaccumulation, as over 95% of the oral dose was excreted in the first 31 hours following 

administration.

Toxicological Effects

Imazethapyr exhibited very low toxicity in mammalian systems. In subchronic and chronic 

toxicity studies in rats and dogs, there were no toxic effects identified [the no observed adverse 

effect level (NOAEL) was set in these studies at the highest dose tested]. There is no evidence 

of increased prenatal susceptibility following in utero exposures to rats and rabbits. In both

studies, there were no developmental effects reported at any dose, and maternal effects 

(increased incidence of clinical signs of toxicity, ulcerations in the stomach and gall bladder, 

increased abortions and maternal deaths) were reported only at the highest doses tested (rabbits: 

1,000 mg/kg/day, rats: 1,125 mg/kg/day). Similarly, in a rat two-generation reproductive 

toxicity study, there were no parental or offspring effects reported at any dose. Although there 

are no neurotoxicity studies available for imazethapyr, there is no indication of neurotoxicity in 

any of the available studies, and neurotoxicity studies for structurally similar compounds 

(imazamox, imazapic, and imazapyr) do not indicate a concern for neurotoxicity. In a rabbit 

dermal toxicity study, there were no effects (local or systemic) up to the highest dose tested. 

There is no evidence that imazethapyr is genotoxic or carcinogenic based on the results of 

adequate studies in mice and rats.

In previous risk assessments, toxicity points of departure were based on NOAELs set either at 

the limit dose or on effects seen at excessively high dose levels (1000 mg/kg/day) not relevant 

for human health risk assessment. Through Registration Review, it has been determined that 

these points of departure are no longer appropriate and no toxicological points of departure will 

be selected for imazethapyr for Registration Review and future actions, and an additional safety 

factor to protect children is not needed. As a result, a quantitative risk assessment is not required 

for imazethapyr for Registration Review to support the currently registered uses.

Conclusions: The toxicology database is adequate to support existing registrations and 

registration review (Attachment 2). No additional toxicological studies are currently required. 

No toxicological points of departure were selected for imazethapyr for Registration Review and 

an additional safety factor to protect children is not needed. As a result, a quantitative risk 

assessment is not required for imazethapyr for Registration Review to support the currently 

registered uses.
Imazethapyr Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 5 of 18

3.0 Residue Chemistry

The nature of the imazethapyr residue in plants, poultry, ruminants, and crayfish is adequately 

understood based on adequate metabolism studies with soybean, green bean, lettuce, 

imidazolinone-tolerant corn, peanut, laying hens, and lactating goats. Based upon these data, the 

HED Metabolism Assessment Review Committee (MARC) concluded that the residue of 

concern in/on canola, soybean, and legume vegetables (Group 6) is imazethapyr. The MARC 

further concluded that the residue of concern in nongrass animal feed (Group 18), peanut, and 

rice are imazethapyr and its metabolites, CL 288511 and CL 182704, both free and conjugated. 

Additionally, the residues of concern in ruminant tissues, corn, crayfish, endive, and lettuce are 

imazethapyr and its metabolite CL 288511 (free and conjugated). Adequate confined field 

rotational crop trial data are available, and support the label-specified plantback intervals (PBIs)

for crops without uses on the imazethapyr label. 

In previous imazethapyr risk assessments, the following data were conditionally required: a 

clover residue data (three field trials), a ruminant feeding study, and a crayfish residue study. In 

2004, a study was submitted that would fulfill the crayfish residue study requirement (Johnston, 

R., 2004, Field Accumulation Study of BAS 685 H (AC 263499 Imazethapyr) and Its Metabolite 

(CL 288511) in Crayfish, Procambarus clarkii: Final Study Report). The other two data 

requirements are no longer considered necessary since a qualitative assessment is sufficient 

based on the low toxicity of imazethapyr. 

Conclusions: 

Adequate residue data are available to support the registered uses of imazethapyr. 

4.0 Dietary Exposure and Risk Assessment

The most recent dietary-exposure assessment was performed for the 2005 human health risk 

assessment (Memo, H. Johnson et al., 11-NOV-2005; D321723) 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.

Conclusions: The dietary-exposure database is adequate to support current registration 

requirements. 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.

5.0 Residential Exposure/Risk Assessment

Imazethapyr is currently registered for use on turf, including areas around schools/universities, 

athletic fields, parks, residential lawns, and golf courses. Residential exposures from these uses 

have not previously been quantitatively assessed. However, since it has been determined that a 

qualitative assessment is sufficient based on the low toxicity of imazethapyr, a quantitative 

residential exposure assessment is not needed for Registration Review for HED to conclude with 

reasonable certainty that residential non-dietary exposures to imazethapyr do not pose a 

significant human health risk.
Imazethapyr Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 6 of 18

Spray Drift

Residential exposures resulting from off-site transport (e.g., spray drift or volatilization) may 

occur as a result of applications of imazethapyr; however, due to the low toxicity of imazethapyr, 

quantitative spray drift and/or bystander assessments are not necessary for Registration Review. 

Conclusions: The residential-exposure database is adequate to support current registration 

requirements. Since it has been determined that a qualitative assessment is sufficient based on 

the low toxicity of imazethapyr, a quantitative residential exposure assessment is not needed for 

Registration Review for HED to conclude with reasonable certainty that residential non-dietary 

exposures to imazethapyr do not pose a significant human health risk.

6.0 Aggregate Exposure/Risk Assessment

The most recent aggregate-risk assessment was performed in conjunction with the November 

2005 human health risk assessment (Memo, H. Johnson et al., 11-NOV-2005; D321723). Since 

no residential uses were assessed previously and there was no acute dietary point of departure for 

imazethapyr, only chronic aggregate assessments were conducted, which took into consideration 

dietary food plus water exposures. Since it has been determined that a qualitative assessment is 

sufficient based on the low toxicity of imazethapyr, a quantitative aggregate risk assessment is 

not needed for Registration Review for HED to conclude with reasonable certainty that 

aggregate exposures to imazethapyr do not pose a significant human health risk. 

Conclusions: Since it has been determined that a qualitative assessment is sufficient based on 

the low toxicity of imazethapyr, a quantitative aggregate exposure assessment is not needed for 

Registration Review for HED to conclude with reasonable certainty that aggregate exposures to 

imazethapyr do not pose a significant human health risk.

7.0 Occupational Exposure/Risk Assessment

Occupational handler and post-application exposures are expected based on the registered

agricultural uses of imazethapyr. Attachment 4 provides a summary of the occupational use 

pattern. The current registrations include some SLN registrations. The application rates range

from 0.003 – 0.095 lb ai/A, and applications can be made either pre- or post-emergence. Most 

labels appear to restrict over-the-top sprays or allow them only up to an early crop stage (i.e., 

when few leaves are present). The most recent occupational risk assessment was performed in 

conjunction with the November 2005 human health risk assessment (Memo, H. Johnson et al., 

11-NOV-2005; D321723)

Since it has been determined that a qualitative assessment is sufficient based on the low toxicity 

of imazethapyr, a quantitative occupational exposure assessment is not needed for Registration 

Review for HED to conclude with reasonable certainty that occupational non-dietary exposures 

to imazethapyr do not pose a significant human health risk.

In accordance with the updated Part 158 data requirements (2007), one or more dislodgeable

foliar residue (DFR) studies are required when a pesticide has occupational uses that could result 

in post-application dermal exposure. However, since no quantitative dermal exposure

assessment is necessary for imazethapyr, a DFR study is not required at this time. 

Imazethapyr has low acute toxicity via the oral, dermal and inhalation routes (Toxicity 

Categories III and IV). It is not an eye (Toxicity Category III) or skin irritant (Toxicity Category 
Imazethapyr Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 7 of 18

IV). Imazethapyr was not shown to be a skin sensitizer. Under 40 CFR 156.208 (c) (2) (iii), 

active ingredients classified as Acute Toxicity III or IV for acute dermal, eye irritation and 

primary skin irritation are assigned a 12-hour REI. Therefore, the [156 subpart K] Worker 

Protection Statement (WPS) interim REI of 12 hours is adequate to protect agricultural workers 

from post-application exposures to imazethapyr. The restricted entry intervals on the registered 

labels for imazethapyr range from 4 to 24 hours. PRD should ensure that the appropriate REI is 

listed on the product labels. Many of the products contain multiple active ingredients, which 

may warrant a longer REI. In addition, while the WPS-recommended REI for imazethapyr based 

on its acute toxicity categories is 12 hours, REIs may be further reduced if certain criteria are met 

for both the technical material and the different end-use products in accordance with the 

Pesticide Registration (PR) Notice 95-3 [Reduction of Worker Protection Standard (WPS) 

Interim Restricted Entry Intervals (REIs) for Certain Low Risk Pesticides]1. Imazethapyr meets 

one of the criteria for a reduction to a 4-hr REI based only on its acute toxicity categories, 

however, during Registration Review, the additional criteria listed in PR Notice 95-3 will be 

checked to ensure they are met for both the active ingredient and the end-use product for those 

products listing a 4-hr REI.

Conclusions: The occupational exposure database is adequate to support the Registration 

Review process for imazethapyr. Since it has been determined that a qualitative assessment is 

sufficient based on the low toxicity of imazethapyr, a quantitative occupational exposure 

assessment is not needed for Registration Review for HED to conclude with reasonable certainty 

that occupational non-dietary exposures to imazethapyr do not pose a significant human health 

risk. During Registration Review, the products listing a 4-hour REI will be checked against the 

criteria listed in PR Notice 95-3 to ensure they are met for both the active ingredient and the enduse product for those products listing a 4-hr REI.

8.0 Public Health and Pesticide Epidemiology Data

Memo, E. Evans, S. Recore, C. Christensen, D416459, 18-DEC-2013.

The OPP Incident Data System (IDS) and the Centers for Disease Control and 

Prevention/National Institute for Occupational Safety and Health (CDC/NIOSH) Sentinel Event 

Notification System for Occupational Risk-Pesticides (SENSOR) databases were consulted for 

pesticide incident data on the active ingredient imazethapyr (PC codes: 128922, 128923). The 

purpose of the database search was to identify potential patterns in the frequency and severity of 

the health effects attributed or potentially attributed to imazethapyr exposure. Imazethapyr is 

also included in the Agricultural Health Study (AHS), and review of studies within the AHS was 

also conducted.

For the Main IDS (which contains incidents resulting in higher severity outcomes and provides 

more detail with regard to case specifics), there were no incidents reported for the single 

chemical active ingredient imazethapyr in the database from January 1, 2008 to September 11, 

2013. There was one incident reported involving more than one chemical including 

imazethapyr. This incident was classified as moderate severity, but due to the nature of the 

report, i.e., multiple chemical exposure, there is little information to glean for the imazethapyr 

risk assessment. In Aggregate IDS (which contains incidents resulting in less severe human 

incidents (minor, unknown, or no effects outcomes)), there were eight reported incidents 

involving imazethapyr from January 1, 2008 to September 11, 2013. These incidents were all 

classified as minor severity. Overall, there are few incidents involving imazethapyr reported to 

 

1 Available: http://www.epa.gov/PR_Notices/pr95-3.html
Imazethapyr Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 8 of 18

IDS. A query of SENSOR-Pesticides from 1998-2009 identified no single ai cases involving 

imazethapyr and one multiple ai case involving imazethapyr. This case was low in severity. The 

low frequency and low severity of acute poisoning cases (also referred to as human incident 

data) reported for imazethapyr in both the IDS and SENSOR-Pesticides does not trigger an EPA 

concern at this time. The Agency will continue to monitor the incident information, and if the 

magnitude and frequency of reported acute poisoning events increases, additional analysis will 

be performed. 

In one Agricultural Health Study (AHS) study, authors observed an elevated risk of bladder and 

colon cancers in relation to imazethapyr use. Authors state the findings are supported by the 

relatedness of imazethapyr to other heterocyclic amine (HCA) compounds, which are putative 

risk factors for these cancers. While this study does show a potential association between bladder 

and colon cancer and imazethapyr use, EPA notes that the HCA structure of imazethapyr is 

unlike the classic structures of the carcinogenic aromatic amines and that the toxicological 

studies submitted to EPA for registration of imazethapyr do not show any evidence of 

carcinogenicity. EPA will continue to monitor the literature for further investigations on this 

topic. 

Conclusions: Based on the low frequency and generally low severity of incident cases reported 

for imazethapyr in both IDS and SENSOR-Pesticides, there does not appear to be a concern at 

this time that would warrant further investigation. The Agency will continue to monitor the 

incident information and if a concern is triggered additional analysis will be conducted during

Registration Review. In addition, the Agency will continue to monitor the literature for further 

investigations relating to potential elevated risk of bladder and colon cancers in relation to 

imazethapyr use.

9.0 Tolerance Assessment and International Harmonization

Current U.S. permanent tolerances (listed in 40 CFR 180.447) are summarized in Attachment 5. 

HED recommends that the following tolerance issues should be considered during Registration 

Review:

1) Tolerances listed for imazethapyr on endive and lettuce should be revoked as there 

are no current registrations for these commodities.

2) Potential for harmonization of U.S. tolerances and Canadian MRLs for canola (or 

rapeseed), field corn grain, and dry lentils.

3) Potential for the establishment of tolerances for residues of imazethapyr in/on the 

oilseed group (group 20) as Canadian MRLs are established for imazethapyr borage 

seeds, cuphea seeds, echium seeds, flaxseeds, gold of pleasure seeds, hare's ear 

mustard seeds, milkweed seeds, mustard seeds (oil seed type), oil radish seeds, poppy 

seeds, sesame seeds, sweet rocket seeds, fenugreek seeds, and sunflower seeds; 

however, the U.S. does not have established tolerances for imazethapyr on these 

commodities.

4) The tolerance expression for imazethapyr should be changed for harmonization 

purposes and to conform to current HED policy. Specifically, the tolerance 

expression for 40 CFR §180.477(all subsections) should be as follows:

Tolerances are established for residues of imazethapyr including its metabolites and 

degradates, applied as its acid or ammonium salt, in or on the commodities listed in the 

following table. Compliance with the tolerance levels specified are to be determined by 

measuring only imazethapyr [(±)-2-[4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-
Imazethapyr Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 9 of 18

imidazol-2-yl]-5-ethyl-3-pyridine carboxylic acid], in or on the following food 

commodities:

10.0 Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in the 

most recent imazethapyr human health risk assessment, in accordance with U.S. Executive Order 

12898, “Federal Actions to Address Environmental Justice in Minority Populations and LowIncome Populations,” 

(http://www.epa.gov/compliance/environmentaljustice/resources/policy/exec_order_12898.pdf). 

The OPP typically considers the highest potential exposures from the legal use of a pesticide 

when conducting human health risk assessments, including, but not limited to, people who obtain 

drinking water from sources near agricultural areas, the variability of diets within the U.S., and 

people who may be exposed when harvesting crops. Should these highest exposures indicate 

potential risks of concern, OPP further refines the risk assessments to ensure that the risk 

estimates are based on the best available information.

11.0 Cumulative

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding for 

imazethapyr and any other substances; and imazethapyr does not appear to produce a toxic 

metabolite produced by other substances. For the purposes of this tolerance action, therefore, 

EPA has assumed that imazethapyr does not have a common mechanism of toxicity with other 

substances. For information regarding EPA’s efforts to determine which chemicals have a 

common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the 

policy statements released by EPA’s Office of Pesticide Programs concerning common 

mechanism determinations and procedures for cumulating effects from substances found to have 

a common mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/.

12.0 Risk Assessment Updates and Data Deficiencies

There are no data deficiencies for imazethapyr. Since it has been determined that no 

toxicological points of departure will be selected for imazethapyr for Registration Review and 

future actions, the Agency does not anticipate the need for conducting any quantitative exposure 

or risk assessments during Registration Review.

13.0 References

Memoranda Relevant to Registration Review.

Author Barcode Date Title

S. Koepke None 02/06/91

PP# 0F3870 Imazethapyr (Pursuit®) In or On Corn Forage, Silage, 

Grain and Fodder. Request for Petition Method Validation Trials 

of Analytical Method SOP M1981.

S. Koepke D170056 02/06/91

Pursuit (Imazethapyr). Review The Submitted Comments of the 

Meeting of October 7, 1991 with Representatives of American 

Cyanamid Company Concerning the Data Requirements for Pursuit 

on Corn and Peanuts.

S. Koepke None 04/01/91

PP# 0F3870 Imazethapyr (Pursuit®) in or on Corn Forage, Silage, 

Grain and Fodder. Evaluation of Analytical Methods and Residue 

Data.
Imazethapyr Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 10 of 18

Memoranda Relevant to Registration Review.

Author Barcode Date Title

S. Koepke None 05/15/91

PP# 0F3870 Imazethapyr (Pursuit®) in or on Corn Forage, Silage, Grain 

and Fodder Results of Petition Method Validation of the hydroxylated 

metabolite (Cl 288,511).

S. Koepke None 08/15/91

PP# 0F3870 Imazethapyr (Pursuit®) in or on Corn Forage, Silage, Grain 

and Fodder. Review of Petitioner's June 20, 1991 Response to 

Deficiencies.

S. Koepke None 09/25/91 Conference of September 25, 1991 with Toxicology Branch I. Discussion 

of Toxicological Significance of Pursuit Metabolites.

S. Koepke D172262 03/03/92

PP# 0F3870 Imazethapyr (Pursuit®) in or on Corn Forage, Silage, Grain 

and Fodder. Review of Petitioner's Responses to Deficiencies dated 

11/19/91.

G. Herndon D189669 4/28/93 ID#: 93FL0007; Section 18 Exemption For Use of Imazethapyr on Lettuce 

and Endive.

F. Griffith, Jr. D167657 05/25/93 PP# 1F4013 - Imazethapyr (Pursuit®) in Alfalfa Hay. Forage, and Seed. 

Review of Analytical Method and Residue Data.

F. Griffith, Jr. D175956 08/18/93

PP# 0F3870 - Imazethapyr (Pursuit®) on Corn Grain, Forage, Fodder, and 

Silage. Review of the Petitioner's Memorandum of Understanding of the 

April 29, 1992, Meeting, Update on Proposed Analytical Method 

Revisions, Draft for Revised Residue Analytical Method, Additional 

Independent Laboratory Validation Data, and Revised Tolerance proposal. 

F. Griffith, Jr. D194534 08/27/93

PP# 1F4013 - Imazethapyr (Pursuit®) in Alfalfa Hay, Forage, and Seed. 

Request for Additional Analytical Reference Standard, Data Detailing

How the Standard Was Characterized, and a Comparison 

Between Standards.

F. Griffith, Jr. D188634 10/13/93 PP# 1F4013 - Imazethapyr (Pursuit®) in Alfalfa Hay, Forage, and Seed. 

Review of the January 28, 1993, Amendment.

F. Griffith, Jr. D196896 11/30/93 ID#: 94CA94006 Section 18 Exemption For Use Of Imazethapyr 

(Pursuit®) On Alfalfa.

F. Griffith, Jr. D197216 02/02/94 PP# 1F4013 - Imazethapyr (Pursuit®) in Alfalfa Forage, Hay and Seed. 

Tolerance Method Validation Requests. 

F. Griffith, Jr. D196948 02/02/94 PP# 1F4013 - Imazethapyr (Pursuit®) in Alfalfa Forage, Hay, and Seed. 

Review of New Residue Analytical Method.

R. Cook D205581 07/21/94

94FL0010. Imazethapyr [Pursuit® Herbicide, EPA Reg. No. 241-310] as 

its ammonium salt in or on lettuce and endive (escarole) in Florida only. 

Submission dated 7/07/94. 

R. Cook D197216 11/08/94

PP# 1F04013. Imazethapyr [Pursuit® Herbicide] in or on Alfalfa Forage, 

Hay and Seed. ACL Tolerance Method Validation Report. March 18, 

1994 and Oct. 17, 1994. 

R. Cook D201538 11/10/94 PP# 1F04013. Imazethapyr [Pursuit® Herbicide] in or on alfalfa forage, 

hay and seed. Review of petitioners response to previous reviews. 

R. Cook D194850 12/13/94

PP# 3E04241. Imazethapyr [Pursuit® Herbicide] as its ammonium salt in 

or on lettuce and endive (escarole) in Florida only. Evaluation of 

Analytical Method and Residue Data. Submission dated 7/06/93. 

R. Cook D210387 01/17/95

PP# 1F04013. Imazethapyr [Pursuit® Herbicide] in or on alfalfa forage, 

hay and seed. Review of petitioners response to previous reviews. DP 

Barcode D210387.

J. Stokes D230401 01/07/97 PP#0F3870. Imazethapyr in/on RAC Corn. Revised Section F dated 

September 23, 1996.

T. Bloem D272022 01/23/2001 ID# 01LA0002: Section 18 for Application of Imazethapyr to Rice. 

Chronic Dietary Exposure Analysis.

P. V. Shah et 

al.

D271177 02/06/2001 ID# 01LA0002 - Section 18 for Application of Imazethapyr to Rice in 

Louisiana. 

T. Bloem D273086 03/13/2001 PP# 0F06186 - Imazethapyr in/on Rice. Petition Method Validation 

(PMV) Request. 

T. Bloem D273086 03/13/2001 PP# 0F06186 - Imazethapyr in/on Rice. Request for a Metabolism Study 

Performed on Imidazolinone-Resistant Rice. 

T. Bloem et al. D280365 01/18/2002

ID#s - 6F04746 (non-grass animal feed),1E06286 (import tolerance; 

imidazolinone-tolerant canola), and 0F06186 (crayfish and imidazolinonetolerant rice) - Imazethapyr in/on Nongrass Feed, Imidazolinone-Tolerant 

Canola (Import), Imidazolinone-Tolerant Rice, and Crayfish. Metabolism 

Assessment Review Committee (MARC) Briefing Document. 

T. Bloem D279832 02/07/2002 ID# 1E06286 - Import Tolerance for Imidazolinone-Tolerant Canola. 
Imazethapyr Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 11 of 18

Memoranda Relevant to Registration Review.

Author Barcode Date Title

Petition Method Validation (PMV) Request.

T. Bloem et al. D280609 03/07/2002

ID#s - 6F04746 (non-grass animal feed), 1E06286 (import tolerance; 

imidazolinone-tolerant canola), and 0F06186 (crayfish and imidazolinonetolerant rice) - Health Effects Division (HED) Metabolism Assessment 

Review Committee (MARC) Decision Document. 

T. Bloem D281431 03/14/2002

Imazethapyr Chronic Dietary Exposure Assessment for the Proposed 

Section 3 Registrations on Imidazolinone-Tolerant Rice (ID # 0F06186), 

Imidazolinone-Tolerant Canola (1E06286), and the non-Grass Animal 

Feed Crop Group (6F04746). 

T. Bloem et al. D282248 04/11/2002

ID#s - 6F04746 (non-grass animal feed), 1E06286 (import tolerance; 

imidazolinone-tolerant canola), and 0F06186 (crayfish and imidazolinonetolerant rice) - Amendment to Health Effects Division (HED) Metabolism 

Assessment Review Committee (MARC) Decision Document - D280609. 

T. Bloem D282112 04/18/2002 PP# 0F06186 - Imazethapyr in/on Rice. Crayfish and Liver Petition 

Method Validation (PMV) Request. 

T. Bloem D278993 04/22/2002

ID#s - 6F04746 (nongrass animal feed crop group), 1E06286 (import 

tolerance; imidazolinone-tolerant canola), and 0F06186 (crayfish and 

imidazolinone-tolerant rice) - Imazethapyr in/on Nongrass Feed, 

Imidazolinone-Tolerant Canola (Import), Imidazolinone-Tolerant Rice, and 

Crayfish. Evaluation of Residue Data and Analytical Methods. 

T. Bloem et al. D232428 04/23/2002

ID#s - 6F04746 (nongrass animal feed crop group), 1E06286 (import 

tolerance; imidazolinone-tolerant canola), and 0F06186 (crayfish and 

imidazolinone-tolerant rice) - Health Effects Division (HED) Risk 

Assessment for Imazethapyr. 

T. Bloem D283383 06/25/2002

ID#s - 6F04746 (nongrass animal feed crop group), 1E06286 (import 

tolerance; imidazolinone-tolerant canola), and 0F06186 (crayfish and 

imidazolinone-tolerant rice) - Imazethapyr in/on Nongrass Feed, 

Imidazolinone-Tolerant Canola (Import), Imidazolinone-Tolerant Rice, and 

Crayfish. Petitioners Response (24-May-2002) to Deficiencies Identified 

in HED’s Residue Chemistry Review (D278993, T. Bloem, 22-Apr-2002). 

T. Bloem D286253 11/21/2002

Imazethapyr (PC Code 128923). Section 3 Registration for Application of 

Imazethapyr (ammonium salt) to Imidazolinone-Tolerant Rice (ID # 

000241-00412). Petitioners Response (17-Oct-2002) to Deficiencies

Identified in the D278933 Residue Chemistry Memorandum. 

T. Bloem D288669 03/20/2003

Imazethapyr (PC Code 128923). Section 3 Registration for Application of 

Imazethapyr (ammonium salt) to Imidazolinone-Tolerant Rice (ID# -

0F06186). Review of a Crayfish Feeding Study Protocol. 

H. Johnson D321721 11/03/2005 Imazethapyr: Chronic Dietary Exposure Assessment for the Section 3 

Registration Tolerance Increase on Rice.

H. Johnson D321723 11/07/2005 Imazethapyr: Human Health Risk Assessment for Tolerance Increase on 

Rice and Crayfish. 

E. Evans et al. D416459 12/19/13 Imazethapyr: Tier I Review of Human Incidents

Attachments: 

Attachment 1: Imazethapyr Identity and Physicochemical Properties.

Attachment 2: Imazethapyr Acute, Subchronic, and Chronic Toxicity Profile.

Attachment 3: Summary of Occupational and Residential Registered Uses.

Attachment 4: Imazethapyr International Residue Limit Status Sheet.

cc: K. Lowe (RAB1), W. Wassell (RAB1), C. Rodriguez (RAB1)

RDI: RAB1 (12/11/13), D. Vogel (12/30/13)

K.Lowe:S10947:PY-S:(703)347-8989:7509P:RAB1
Imazethapyr Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 12 of 18

Attachment 1: Imazethapyr Identity and Physicochemical Properties.

Imazethapyr Nomenclature.

Imazethapyr

Chemical structure

Common name Imazethapyr

IUPAC name (±)-5-ethyl-2-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl) nitotinic acid

CAS name (±)-2-[4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl]-5-ethyl3-pyridinecarboxylic acid

CAS registry number 81335-77-5

Imazethapyr salt

Chemical structure

Common name Imazethapyr ammonium

IUPAC name ammonium 5-ethyl-2-[(RS)-4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-

yl]nicotinate

CAS name ammonium 2-[4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl]-

5-ethyl-3-pyridinecarboxylate

CAS registry number 101917-66-2

Physicochemical Properties of the Technical Grade Test Compound: Imazethapyr

Parameter Value Reference

Melting range 169 – 173oC D321723, 11/7/05, H. Johnson

pH Not available

Density 0.459 g/ml D321723, 11/7/05, H. Johnson

Water solubility 0.14 g/100 ml (distilled) D321723, 11/7/05, H. Johnson

Solvent solubility Not available

Vapor pressure 1 x 10-7 mm Hg at 60oC D321723, 11/7/05, H. Johnson

Dissociation constant, pKa Not available

Octanol/water partition 

coefficient

11 at pH 5; 31 at pH 7; 16 at 

pH 9

D321723, 11/7/05, H. Johnson

UV/visible absorption spectrum Not available
Imazethapyr Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 13 of 18

Attachment 2: Imazethapyr Acute, Subchronic, and Chronic Toxicity Profile

Acute Toxicity Profile- Imazethapyr Technical.

Guideline

No. Study Type MRID # Results Toxicity Category

870.1100 Acute Oral 00159375 LD50 5,000 mg/kg

(male and female rats) IV

870.1200 Acute Dermal 00159375 LD50 2,000 mg/kg

(male and female rabbits) III

870.1300 Acute Inhalation 00159378 LD50 3.27 mg/L

(male and female rats) III

870.2400 Primary Eye Irritation 00159375 Not an irritant III

870.2500 Primary Skin Irritation 00159375 Not an irritant IV

870.2600 Dermal Sensitization 00159379 Not a skin sensitizer N/A

Subchronic, Chronic, or Other Toxicity Profile of Imazethapyr.

Guideline No./ 

Study Type

MRID No. (year)/

Classification /Doses Results

870.3100

90-Day oral toxicity 

rodents-rat

00159381 (1986)

Acceptable/guideline

0, 1,000, 5,000, or 10,000 ppm

0, 50, 250, or 500 mg/kg/day

NOAEL = 500 mg/kg/day (HDT).

LOAEL = not observed.

870.3150

90-Day oral toxicity 

nonrodents-dog

00159382 (1985)

Acceptable/guideline

0, 1,000, 5,000 or 10,000 ppm

0, 25, 125 or 250 mg/kg/day

NOAEL = 250 mg/kg/day (HDT).

LOAEL = not observed.

870.3200

21-Day dermal 

toxicity-rabbit

00159383 (1985)

Acceptable/guideline

0, 50, 200, or 1000 mg/kg/day

0, 54.8, 219.3, or 1096.5 

mg/kg/day (adjusted for purity)

NOAEL = 1096 mg/kg/day (HDT).

LOAEL = not observed.

870.3700a

Prenatal 

developmental in 

rodents- rat

40429417 (1985)

Acceptable/guideline

0, 125, 375, or 1125 mg/kg/day

Maternal: NOAEL= 375 mg/kg/day.

LOAEL1= 1,125 mg/kg/day based on increased 

incidences of clinical signs during the gestation.

Developmental: NOAEL = 1,125 mg/kg/day.

LOAEL = not observed.

870.3700b Prenatal 

developmental in 

nonrodents- rabbit

00159384 (1986)

Acceptable/guideline

0, 100, 300, or 1,000 mg/kg/day

Maternal: NOAEL = 300 mg/kg/day.

LOAEL1= 1,000 mg/kg/day based on an increased 

incidence of clinical signs during gestation, ulcerations 

in the mucosal layer of the stomach and gall bladder, 

increased abortions, and maternal deaths.

Developmental: NOAEL = 1,000 mg/kg/day (HDT).

LOAEL = not observed.

870.3800 

Reproduction and 

fertility effects- rat

40429418 (1987)

Acceptable/guideline

0, 1,000, 5,000 or 10,000 ppm

0, 50, 250 or 500 mg/kg/day

Parental/Systemic NOAEL = 500 mg/kg/day (HDT).

LOAEL = not observed.

Reproductive NOAEL = 500 mg/kg/day (HDT).

LOAEL = not observed.

Offspring NOAEL = 500 mg/kg/day (HDT).

LOAEL = not observed.

870.4100b Chronic 

toxicity- dog

40429416 (1987)

Acceptable/guideline

0, 1,000, 5,000 or 10,000 ppm

0, 25, 125, or 250 mg/kg/day

NOAEL = 250 mg/kg/day (HDT).

LOAEL = not observed.

870.4300 Chronic/

Carcinogenicity- rat

40429414 (1987)

Acceptable/guideline

0, 1,000, 5,000, or 10,000 ppm

0, 50, 250, or 500 mg/kg/day

NOAEL = 500 mg/kg/day (HDT).

LOAEL = not observed.

No evidence of carcinogenicity.
Imazethapyr Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 14 of 18

Subchronic, Chronic, or Other Toxicity Profile of Imazethapyr.

Guideline No./ 

Study Type

MRID No. (year)/

Classification /Doses Results

870.4300 

Carcinogenicitymouse

40429415 (1987)

Acceptable/guideline

0, 1,000, 5,000, or 10,000 ppm

0, 150, 750, or 1500 mg/kg/day

NOAEL = 750 mg/kg/day.

No evidence of carcinogenicity at doses tested.

870.5100 Gene 

Mutation

00159719 (1986)

Acceptable/guideline

0, 50, 158, 500, 1000, 1581, 3162 

or 5,000 μg/plate

Non-mutagenic when tested up to 5000 ug/plate, in 

presence and absence of metabolic activation, in S. 

typhimurium strains TA98, TA100, TA1535, TA1537, 

and TA 1538 and E.coli strain WP2uvra.

870.5300 Gene 

Mutation

40429419 (1986)

Acceptable/guideline

up to 3333 μg/mL (limit of 

solubility) and 4000 μg/mL 

(beyond limit of solubility)

Negative for induction of forward mutation at the 

HPRT locus in Chinese hamster ovary cells, in the 

presence or absence of S9-activation at doses up to 

limit of solubility (3333 μg/mL) and beyond (4000 

μg/mL).

870.5375 

Chromosome 

aberration

40438201 (1986)

Acceptable/guideline

0, 1.14, 1.71, 1.82, 2.05, and 2.28 

mg/ml with and without S9 

activation

Did not induce structural chromosome aberration in 

Chinese hamster lung (V79) cell cultures in the 

presence and absence of activation up to cytotoxic 

concentrations.

870.5450 Dominant 

Lethal Assay

00159720 (1985)

Unacceptable/guideline

0, 200, 1000 or 2000 mg/kg

Negative for dominant lethal effects (chromosomal 

damage) at doses up to 2000 mg/kg.

870.5550

Other Genotoxicity

00159721 (1985)

Acceptable/guideline

0, 0.13, 0.4, 1.3, 4.0, 13, 40, 133, 

400, 1333, or 4000 μg/mL

No evidence that unscheduled DNA synthesis was 

induced by imazethapyr, as determined by radioactive 

tracer procedures [nuclear silver grain counts].

870.7485 

Metabolism and 

pharmacokinetics –

rat

40429420 and 41467703 (1987)

5.7 mg/kg single dose;

1000 mg/kg single dose and 3 

daily doses of 250 mg/kg 

followed by a single dose of 1000 

mg/kg;

1000 mg/kg/day single and 

repeated dose

In a rat metabolism study, almost 100% of the 

administered radiolabeled test material was recovered 

in the excreta within 96 hours (89-95% in the urine and 

6-11% in the feces). Greater than 95% of the oral dose 

was excreted in the first 31 hours. The major residue in 

both urine and feces was the parent compound. 

Approximately 2% of the oral dose was metabolized 

and excreted as CL 288511 (1-hydroxy ethyl derivative 

of AC 263,499, parent).

A high percentage of the administered material was 

excreted in the urine as the unmodified parent 

compound (>97%) and a very small amount as the CL 

288511. In the high dose group, the unmodified parent 

compound was the major fecal component in both 

sexes, particularly at 12 hours or less. The CL 288511 

was the major metabolite. One unknown was also 

found in significant quantities. In the low dose group, 

six components were found in the feces: parent 

compound, the CL 288511, the unknown previously 

mentioned and several minor unknowns.

1 The LOAELs from these studies were greater than or equal to the limit dose of 1000 mg/kg/day and, in 

combination with the low toxicity of other toxicity studies, are therefore considered not relevant for human health 

risk assessment.
Imazethapyr Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 15 of 18

Attachment 3: Summary of Occupational and Residential Registered Uses 

Crop/Use Site Formulation Application method Maximum App 

Rate (lb ai/A) REI

Imazethapyr

Alfalfa

Liquid ground and aerial (no 

chemigation)

0.094 48 hours

WSP 0.095 12 hours

Clearfield and IMI corn hybrids

DF ground and aerial (no 

chemigation) 0.063 12 - 48 hours

Liquid aerial, ground, dry bulk 

fertilizer (no chemigation) 0.063 24 -48 hours

Clearfield rice DF ground and aerial (no 

chemigation) 0.094 12 hours

Clover DF ground and aerial (no 

chemigation) 0.095 12 hours

Forage Legumes and Grasses (Federal 

Conservation Reserve Program and 

Agricultural Reserve Program Land)

DF ground and aerial (no 

chemigation) 0.063 12 hours

Peanuts

Liquid ground and aerial (no 

chemigation)

0.050 12 hours

DF 0.063 12 hours

Peas and Beans 

WSP

aerial and ground (no 

chemigation; aerial is 

prohibited for red kidney 

beans and snap beans)

0.063 12 hours

DF ground only (no aerial or 

chemigation) 0.047

12 hours

Liquid

24 hours

ground and aerial (no 

chemigation) 0.031 12 hours

Residential, Commercial and 

institutional Lawns, Athletic Fields, 

Commercial Sod Farms, Golf Course 

Fairways and Roughs, Railroad 

Rights-of-Way, Highway, Roadside, 

Pipeline and Utility Rights-of-Way, 

Industrial Areas, Fence Rows and 

Other Non-crop Sites 

Liquid Aerial, Groundboom, 

Handheld (no chemigation) 0.075 NS

Soybeans

DF and WSP ground and aerial (no 

chemigation) 0.063 12 hours

Liquid aerial, ground, dry bulk 

fertilizer (no chemigation) 0.064 12 - 48 hours

Imazethapyr Salt

Alfalfa Liquid ground and aerial (no 

chemigation) 0.094 4 hours

Clearfield rice Liquid ground and aerial (no 

chemigation) 0.094 4 hours

Clearfield corn hybrids Liquid ground and aerial (no 

chemigation) 0.063 4 hours

Clover Liquid ground and aerial (no 

chemigation) 0.094 4 hours

Edamame Liquid ground and aerial (no 

chemigation) 0.063 4 hours

Forage legumes and grasses Liquid ground and aerial (no 

chemigation) 0.063 4 hours

Highway rights of way, land around 

schools/universities, libraries, 

hospitals, commercial/industrial areas, 

Liquid Aerial, ground (no 

chemigation) 0.003 NA
Imazethapyr Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 16 of 18

Crop/Use Site Formulation Application method Maximum App 

Rate (lb ai/A) REI

athletic fields, parks, golf course 

roughs

Legume (trefoil) Liquid ground and aerial (no 

chemigation) 0.063 4 hours

Peanuts Liquid ground and aerial (no 

chemigation) 0.063 4 hours

Peas and Beans (some restrictions by 

specific variety) Liquid

ground and aerial (no 

chemigation; no aerial for 

kidney or snap beans)

0.063 4 hours

Soybeans Liquid ground and aerial (no 

chemigation) 0.063 4 -24 hours
Imazethapyr Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 17 of 18

Attachment 4: Imazethapyr International Residue Limit Status Sheet.

International Residue Limits

(128922/128923; 10/23/2013)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex

40 CFR 180.447

(a) General. (1) imazethapyr, 2-[4,5-dihydro4-methyl-4-(1-methylethyl)-5-oxo-1Himidazol-2-yl]-5-ethyl-3-pyridine carboxylic 

acid, applied as its acid or ammonium salt

(±)-2-[4,5-dihydro-4-methyl-4-(1-

methylethyl)-5-oxo

-1H-imidazol-2-yl]-5-ethyl-3-

pyridinecarboxylic acid,

expressed as ammonium salt

None

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico2 Codex

Canola, seed10.10 0.05 rapeseeds (canola)

Soybean 0.1 0.1 dry soybeans

Vegetable, legume, group 6 0.1 0.1 Dry (Dutch brown beans, adzuki 

beans, black beans, cranberry 

beans, kidney beans, lima beans, 

navy beans, pink beans, pinto 

beans, red beans, soybeans, tepary 

beans, white beans, yelloweyed 

beans), peas; Edible-podded 

(runner beans, snap beans, wax 

beans); succulent shelled lima 

beans

0.05 dry lentils

(2) Sum of the residues of the herbicide 

imazethapyr, 2-[4,5-dihydro-4-methyl-4-(1-

methylethyl)-5-oxo-1H-imidazol-2-yl]-5-

ethyl-3-pyridine carboxylic acid; its 

metabolite CL 288511, 2-[4,5-dihydro-4-

methyl-4-(1-methylethyl)-5-oxo-1H-imidazol2-yl]-5-(1-hydroxyethyl)-3-pyridine 

carboxylic acid; and its metabolite CL 

182704, 5-[1-(beta-Dglucopyranosyloxy)ethyl]-2-[4,5-dihydro-4-

methyl-4-(1-methylethyl)-5-oxo-1H-imidazol2-yl]-3-pyridinecarboxylic acid, applied as its 

acid or ammonium salt

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico2 Codex

Alfalfa, seed 0.15

Alfalfa, seed screenings 0.15

Animal feed, nongrass, group 18, 

forage

3.0

Animal feed, nongrass, group 18, hay 5.5

Peanut 0.1

Rice, bran 1.2

Rice, grain 0.3

Rice, straw 0.4
Imazethapyr Registration Review Human Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 18 of 18

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex

(3) Sum of residues of the herbicide 

imazethapyr, 2-[4,5-dihydro-4-methyl-4-(1-

methylethyl)-5-oxo-1H-imidazol-2-yl]-5-

ethyl-3-pyridine carboxylic acid, and its 

metabolite CL 288511, 2-[4,5-dihydro-4-

methyl-4-(1-methylethyl)-5- oxo-1Himidazol-2-yl]-5-(1-hydroxyethyl)-3-pyridine 

carboxylic acid, applied as its acid or 

ammonium salt

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico2 Codex

Cattle, meat byproducts 0.10 

Corn, field, forage 0.1

Corn, field, grain 0.1 0.05

Corn, field, stover 0.1

Crayfish 0.15

Goat, meat byproducts 0.10

Hog, meat byproducts 0.10

Horse, meat byproducts 0.10

Sheep, meat byproducts 0.10

MRLs with NO US Equivalent

Borage seeds, cuphea seeds, echium 

seeds, flaxseeds, gold of pleasure 

seeds, hare's ear mustard seeds, 

milkweed seeds, mustard seeds (oil 

seed type) , oil radish seeds, poppy 

seeds, sesame seeds, sweet rocket 

seeds

0.05

Fenugreek seeds 0.05

Sunflower seeds 0.1

Completed: M. Negussie; 10/29/13

1 There are no U.S. registrations for canola as of March 21, 2003.

2 Mexico adopts U.S. tolerances and/or Codex MRLs for its export purposes.

NOTE: The following tolerances are listed in 40 CFR 180.447; however, there are no current registrations 

and these should be removed.

(c) Tolerances with regional registrations. Tolerances with regional registration, as defined in §180.1(l) of this 

chapter, are established for the sum of residues of the herbicide imazethapyr, 2- [4,5-dihydro-4-methyl-4-(1-

methylethyl)-5-oxo-1H-imidazol-2-yl]-5-ethyl-3-pyridine carboxylic acid, as its ammonium salt, and its metabolite, 

2- [4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl]-5-(1-hydroxyethyl)-3-pyridine carboxylic 

acid, both free and conjugated, applied as its acid or ammonium salt, in or on the following raw agricultural 

commodities: 

Commodity Parts per million

Endive 0.1

Lettuce, head 0.1

Lettuce, leaf 0.1