UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: 5-JUNE-20 14 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Imazamox. Human-Health Assessment Seeping Document in Support of 

Registration Review. 

PC Code: 129171 

Decision No.: 486514 

Petition No.: N/A 

DP Barcode: D417140 

Registration No.: RegRev-7238-1 

Regulatory Action: Registration Review Scoping Document 

Risk Assessment Type: N/ A Case No.: 7238 

TXRNo.: N/A CAS No.: 114311-32-9 

MRID No.: N/A 40 CFR: § 180.1223 

FROM: Lata Venkateshwara, Environmental Scientist 

William D. Wassell, Chemist 

Risk Assessment Branch 1 (RAB 1) 

Health Effects Division (HED, 7509P) 

THROUGH: Charles W. Smith III, Branch Chief e__:_ George F. Kramer, Ph.D., Senior Chemi~ ~ 

RABIIHED (7509P) 

TO: Kelly Ballard, Chemical Review Manager 

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

Attached is HED's scopingdocument for imazamox to support Registration Review. 

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lmazamox Registration Review Human-Health Assessment Scoping Document 

Executive Summary 

HED has prepared a scoping document to support Registration Review of the herbicide 

imazamox. Imazamox is the common name of the active ingredient ammonium salt ofimazamox 

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

pyridinecarboxylic acid). lmazamox is registered for use on alfalfa, beans (dry), chicory, clover 

grown for seed, edamame, lima bean (succulent) peas (dry), pea (English), snap bean, soybean, 

canola, lentil, rice, sunflower and wheat. It is also registered for control of vegetation in and 

around aquatic and noncropland sites including areas that may be grazed or cut for hay. In 

addition, there are three Special Local Needs (SLN) Registrations for imazamox: AR130001 

provides control of weeds in edamame, CA070005 provides suppression in Ladino clover grown 

for seed, and FL090007 provides for increased residues of imazamox in irrigation water resulting 

from application to irrigation canals. Imazamox is applied by ground or aerial application and 

may be applied postemergence. 1 lmazamox is exempt from the requirement of a tolerance on all 

food commodities when applied as a herbicide in accordance with good agricultural practices. 

The most recent human-health risk assessment was performed in 2001, and was for new uses on 

alfalfa, canola, legume vegetables and wheat (Memo, W. Donavan et al. , 13-AUG-2001; 

D276570). There is currently one pending PRIA action for imazamox. This action is for an 

increased maximum rate for Clearfield® Plus on sunflowers. The PRIA due date is September 

11 , 2014. 

HED has evaluated the status of the human-health assessments for imazamox 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 

imazamox 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 

(FQP A) Safety Factor (SF) evaluation. lmazamox exhibits low toxicity in mammalian systems. 

No additional toxicological ·studies are currently required. Since no effects were seen in any 

guideline toxicity studies, no toxicological points of departure (PODs) were selected for 

imazamox and, as a result, a quantitative risk assessment is not required for imazamox for 

Registration Review to support the currently registered uses. 

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

current registration requirements. As per 40 CFR §180.1223, imazarnox is exempt from the 

requirement of a tolerance on all food commodities when applied as a herbicide in accordance 

with good agricultural practices. Thus, residue chemistry data for imazamox are not required. 

Currently, a quantitative dietary exposure assessment is not required as toxicological PODs have 

not been identified for imazamox. 'Since it has been determined that a qualitative assessment is 

sufficient based on the low toxicity of imazamox, a quantitative dietary exposure assessment is 

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

exposures to imazamox 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. In the August 2001 human-health risk assessment, occupational 

1 EPA factsheet found online at: http://www.epa.gov/opp00001/chem_search/reg_actions/registrationlfs_PC129171_22-May-97.pdf 

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Imazamox Registration Review Human-Health Assessment Scoping Document

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exposures were qualitatively assessed since no toxicological PODs were identified for 

imazamox. 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 

imazamox, neither quantitative occupational nor residential exposure assessments are needed for 

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

occupational exposures to imazamox do not pose a significant human-health risk. 

With regard to public health and pesticide epidemiology data, based on the low frequency and 

low severity of incident cases reported for imazamox in both the OPP Incident Data System 

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

Sentinel Event Notification System for Occupational Risk-Pesticides (SENSOR)-Pesticides, 

there does not appear to be a concern at this time that would warrant further investigation. HED

will continue to monitor the incident information and if a concern is triggered then additional 

analysis will be conducted during Registration Review. 

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

PODs will be selected for imazamox for Registration Review and future actions; HED does not 

anticipate the need for conducting any quantitative exposure or risk assessments during 

Registration Review.

1.0 Introduction

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

enzyme acetohydroxyacid synthetase (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. Imazamox is registered for use on 

alfalfa, beans (dry), chicory, clover grown for seed, edamame, lima bean (succulent) peas (dry), 

pea (English), snap bean, soybean, canola, lentil, rice, sunflower and wheat. It is also registered 

for control of vegetation in and around aquatic and noncropland sites including areas that may be 

grazed or cut for hay. In addition, there are three SLN Registrations for imazamox: AR130001 

provides control of weeds in edamame, CA070005 provides suppression in Ladino clover grown 

for seed, and FL090007 provides for increased residues of imazamox in irrigation water. The 

most recent human-health risk assessment was performed in 2001, and was for new uses on 

alfalfa, canola, legume vegetables and wheat (Memo, W. Donavan et al., 13-AUG-2001; 

D276570). There is currently one pending PRIA action for imazamox. This action is for an 

increased maximum rate for Clearfield® Plus sunflowers. The PRIA due date is September 11, 

2014. The structure, chemical names, and other identifiers as well as the physical/chemical 

properties of imazamox can be found in Attachment 1.

2.0 Hazard Characterization/Assessment

The pesticidal mode of action of imazamox involves inhibition of AHAS, which is a key plant 

enzyme in the biosynthesis of the amino acids leucine, isoleucine, and valine. Mammals lack 

this biosynthetic pathway and must obtain these amino acids from their diet. The low toxicity 

exhibited by imazamox is consistent with the proposed pesticidal mode of action and the lack 

thereof in mammalian systems.

Toxicological Studies Available for Analysis

The Hazard Identification Assessment Review Committee (HIARC) met in July 2001 (HED 

Doc. No. 014611, P.V. Shah, 11-JUL-2001) to discuss the appropriate endpoints and PODs for 
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imazamox. At that time, no additional toxicity data were deemed required because of the low 

toxicity exhibited by imazamox. As part of the revised 40 CFR Toxicology Data Requirements, 

inhalation, neurotoxicity (acute and subchronic), and immunotoxicity studies are necessary for 

registration; however the Hazard and Science Policy Council (HASPOC) concluded using a 

weight-of-evidence approach that these studies are not required at this time. (M.Perron; 18-

MAR-2014, TXR#0056929). 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, imazamox was extensively absorbed following intravenous 

or oral dosing as reflected by the high percentage excreted in the urine (75%) within 24 hours of 

dosing. Within 168 hours of dosing, 88-99% of the administered dose was recovered (74-91% in 

urine). Metabolism of the parent chemical was minimal as the major residue excreted in both 

urine and feces was the parent chemical.

Toxicological Effects

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

toxicity studies in rats and dogs, there were no toxic effects identified. There is no evidence of 

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

there were no developmental or maternal effects reported at any dose (highest dose tested was 

1,000 mg/kg/day in rats and 900 mg/kg/day in rabbits). Similarly, in a rat two-generation 

reproductive toxicity study, there were no parental or offspring effects reported up to 1,705 

mg/kg/day in females and 1,469 mg/kg/day in males. No toxicity was seen at doses exceeding 

the limit-dose in long-term studies in mice (1,053 mg/kg/day), rats (1,068 mg/kg/day), and dogs 

(1,156 mg/kg/day). In a rat dermal toxicity study, there were no effects (local or systemic) up to 

the highest dose tested (1,000 mg/kg/day). Although there are no neurotoxicity studies 

available for imazamox, there is no indication of neurotoxicity in any of the available studies. 

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

in mice and rats.

The HIARC met in July 2001 (HED Doc. No. 014611, P.V. Shah, 11-JUL-2001) to discuss the 

appropriate endpoints and PODs for imazamox. At this meeting, it was determined that no 

effects were seen in any of the guideline toxicity studies and thus no PODs or additional SF to 

protect children were needed for imazamox. As a result, quantitative risk assessment is not 

required for imazamox. In addition, it was determined that the toxicological profile of imazamox 

supports a tolerance exemption for this chemical. 

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

Registration Review (Attachment 2). No additional toxicological studies are currently required. 

Since no effects were seen in any guideline toxicity studies, no toxicological PODs will be 

selected for imazamox and as a result, a quantitative risk assessment is not required for 

imazamox for Registration Review to support the currently registered uses.

3.0 Residue Chemistry

As per 40 CFR §180.1223, imazamox is exempt from the requirement of a tolerance on all food 

commodities when applied as a herbicide in accordance with good agricultural practices. Thus, 

residue chemistry data for imazamox are not required. 
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4.0 Dietary Exposure and Risk Assessment

Currently, a quantitative dietary exposure assessment is not required as toxicological endpoints 

of concern have not been identified for imazamox. Since it has been determined that a 

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

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

certainty that dietary exposures to imazamox 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 imazamox, a quantitative dietary exposure assessment is not needed for 

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

imazamox do not pose a significant human-health risk.

5.0 Residential Exposure/Risk Assessment

Imazamox is currently registered for control of vegetation in aquatic sites. Aquatic sites that 

may be treated include estuarine and marine sites, ponds, lakes, reservoirs, wetlands, marshes, 

swamps, bayous, arroyos, ditches, canals, streams, rivers, creeks and other slow-moving or 

quiescent bodies of water. 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 imazamox, a quantitative residential exposure assessment 

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

residential non-dietary exposures to imazamox do not pose a significant human-health risk.

Spray Drift

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

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

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 imazamox, a quantitative residential exposure assessment is not needed for 

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

exposures to imazamox do not pose a significant human-health risk.

6.0 Aggregate Exposure/Risk Assessment

In the November 2001 human-health risk assessment (Memo, W. Donavan et al., 13-AUG-2001; 

D276570), a quantitative aggregate assessment was deemed unnecessary since no toxicological 

PODs were selected for imazamox. Since it has been determined that a qualitative assessment is 

sufficient based on the low toxicity of imazamox, a quantitative aggregate exposure assessment 

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

aggregate exposures to imazamox 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 imazamox. Imazamox is also currently registered for control of vegetation in 
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aquatic sites. Attachment 4 provides a summary of the occupational use pattern. The current 

registrations include three active SLN registrations. The commercial formulations include 

Raptor®, Raptor® DG, Clearcast®, Beyond® and Clearmax®. Occupational exposures were 

qualitatively assessed in the 2001 human-health risk assessment since no toxicological PODs 

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

the low toxicity of imazamox, a quantitative occupational exposure assessment is not needed for 

Registration Review for HED to conclude with reasonable certainty that occupational nondietary exposures to imazamox 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 imazamox, a DFR study is not required at this time. 

Imazamox 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 IV). 

Imazamox was not shown to be a skin sensitizer. Under 40 CFR 156.208 (c) (2) (iii), ai’s 

classified as Acute Toxicity III or IV for acute dermal, eye irritation and primary skin irritation 

are assigned a 12-hour restricted entry interval (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 imazamox. The REIs on the registered labels for imazamox

range from 4 to 12 hours. While the WPS-recommended REI for imazamox 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]2. Imazamox meets one of the 

criteria for a reduction to a 4-hour 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 ai and the end-use product for those products listing a 4-hour 

REI.

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

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

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

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

that occupational exposures to imazamox 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 end-use product 

for those products listing a 4-hr REI.

8.0 Public Health and Pesticide Epidemiology Data

Memo, E. Evans, S. Recore, D417802, 6-FEB-2014.

The OPP IDS and the Centers for Disease Control and Prevention/National Institute for 

Occupational Safety and Health (CDC/NIOSH) SENSOR databases were consulted for pesticide 

incident data on the active ingredient imazamox (PC codes: 129171). 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 imazamox exposure. 

 

2 Available: http://www.epa.gov/PR_Notices/pr95-3.html
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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 ai imazamox in the database from January 1, 2009 to January 15, 2014. In Aggregate 

IDS (which contains incidents resulting in less severe human incidents (minor, unknown, or no 

effects outcomes)), there were no reported incidents involving imazamox from January 1, 2009

to January 15, 2014. Overall, there are no incidents involving imazamox reported to IDS. A 

query of SENSOR-Pesticides from 1998-2010 identified one single ai case involving imazamox

and no multiple ai cases involving imazamox. 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 

imazamox in both the IDS and SENSOR-Pesticides does not trigger an EPA concern at this time. 

HED will continue to monitor the incident information, and if the magnitude and frequency of 

reported acute poisoning events increases, then additional analysis will be performed. 

Imazamox is not included in the Agricultural Heath Study (AHS). 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 imazamox in both IDS and SENSOR-Pesticides, there does not appear to be a concern at this 

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

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

Registration Review. 

9.0 Tolerance Assessment and International Harmonization

Tolerances are not established for residues of imazamox on food or feed commodities in the U.S.

as imazamox is exempt from the requirement of a tolerance on all food commodities when 

applied as a herbicide in accordance with good agricultural practices. Canadian Maximum 

Residue Limits (MRLs) are established for residues of imazamox in/on borage seeds, dry beans 

and peas, dry lentils, dry soybeans, sunflower seed, wheat, and poultry and ruminant 

commodities (see Attachment 4). The Canadian MRL expression includes residues of imazamox 

only. Mexico and Codex have not established MRLs for residues imazamox. HED concludes 

international harmonization is not an issue for imazamox.

10.0 Environmental Justice

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

most recent imazamox 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
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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 

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

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

EPA has assumed that imazamox 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 imazamox. Since it has been determined that no toxicological 

PODs will be selected for imazamox for Registration Review and future actions; HED 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

R. Cook D203639 12/09/94

PP4G4350. AC 299263 [2-[4,5-dihydro-4-methyl-4-(1-methylethyl)-5-

oxo-1H-imidazol-2-yl]-5-methoxymethyl-3-pyridinecarboxylic acid, 

formulated as ammonium salt] for use on soybeans. EUP and temporary 

tolerance: Evaluation of Product Chemistry Data.

R. Cook D205708 3/28/95

PP4G4350. AC 299263 [2-[4,5-dihydro-4-methyl-4-(1-methylethyl)-5-

oxo-1H-imidazol-2-yl]-5-methoxymethyl-3-pyridinecarboxylic acid, 

formulated as ammonium salt] for use on soybeans. EUP and temporary 

tolerance: Evaluation of Residue Chemistry Data. 

R. Cook D212351 02/27/95 Multiresidue Method (MRM) Validation Data For AC 299,263).

R. Cook D212349 03/02/95 PP4G4350 - AC 299,263 [(±)-2-[4,5-dihydro-4-methyl-4-(1-methylethyl)-

5-oxo-1H-imidazol-2-yl]-5-methoxymethyl-3-pyridinecarboxylic acid].

D. McCall D222198 03/26/96 New Chemical Screen for AC 299.263 Toxicology and Chemistry Data 

Requirements.

R. Cook D224405 5/20/96 PP4G3350. AC 299,263 in soybeans. Review of Petition Method 

Validation (Confirmation) Report.

R. Cook D227228 07/03/96 PP4G4350. AC 299,263 in Soybeans. Review of Petition Method 

Validation Report.

R. Cook None 07/10/96 AC 299,263 . Issues to be presented to the HED Metabolism Committee.

R. Cook D225340 8/6/96

PP#6F4649. AC 299263 [2-[4,5-dihydro-4-methyl-4-(1-methylethyl)-5-

oxo-1H-imidazol-2-yl]-5-methoxymethyl-3-pyridinecarboxylic acid, 

formulated as ammonium salt] for use on soybeans. Permanent Tolerance 

and Registration: Evaluation of Residue Chemistry Data. 

G. Tompkins D233731 03/12/97 Perform Occupational and Residential Exposure Assessment for New 

Herbicide –AC299,263.

B. Madden D222186 05/09/97 Imazamox – 129171: Health Effects Division Risk Characterization for 

Use of the New Chemical Imazamox in/on Soybeans (6F4649).

W. Donovan D253305 02/19/99 Imazamox - Chronic Dietary Exposure Analysis. 

O. Odiott et al.

D252590, 

D252608, 

D252613, 

D252631

02/26/99

ID#99CA0010. Section 18 Exemption for the Use of Imazamox on IMITM 

(Imidazolinone Tolerant) Canola to Control Wild Mustard in North Dakota 

and Minnesota ; and In Dry Beans to Control Nightshade Species in 

Wyoming and Montana.

W. Donovan D252590 02/26/99

ID# 99CA0010. Section 18 Exemption For The Use Of Imazamox On 

ImiTM (Imidazolinone Tolerant) Canola To Control Wild Mustard In North 

Dakota And Minnesota; And In Dry Beans To Control Nightshade Species 

In Wyoming And Montana. 
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Memoranda Relevant to Registration Review.

Author Barcode Date Title

W. Donovan D253418 04/05/99

ID#UT990001. Section 24(c) Special Local Needs Registration. 

Imazamox in/on Alfalfa Grown for Seed. Determination of Food/NonFood Use. 

W. Donovan D274996 05/23/01 PP# 0F06088. Imazamox in/on Alfalfa, Canola, Legume Vegetables, and 

Wheat. Request for Petition Method Validation (PMV).

P.V. Shah

HED Doc. 

No. 

014611

07/11/01 Imazamox-Report of the Hazard Identification Assessment Review 

Commitee

W. Donovan D263875 07/26/01 PP# 0F06088. Imazamox use on Alfalfa, Canola, Legume Vegetables, and 

Wheat. Evaluation of Residue Data and Analytical Methods. 

W. Donovan D276570 08/13/01 PP#0F06088. Imazamox in/on Alfalfa, Canola, Legume Vegetables, and 

Wheat. HED Risk Assessment.

W. Donovan D278055 09/27/01

PP# 0F06088. Addendum To “Imazamox In/On Alfalfa, Canola, Legume 

Vegetables, And Wheat. HED Risk Assessment, D276570, 13-AUG2001.” 

W. Wassell D371544 03/05/10 Imazamox (129171); Registration No.: 241-437. Label Amendment For 

An Increase in Application Rate to Aquatic and Terrestrial Non-crop Sites.

E. Evans et al. D417802 02/06/14 Imazamox: Tier I Review of Human Incidents

M. Perron TXR

0056929 3/18/14

Imazamox: Summary of Hazard and Science Policy Council (HASPOC) 

Meeting of March 13, 2014: Recommendations on the requirement of a 28-

day inhalation study, neurotoxicity (acute and subchronic), and 

immunotoxicity studies.

Attachments: 

Attachment 1: Imazamox Identity and Physicochemical Properties.

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

Attachment 3: Summary of Occupational and Residential Registered Uses.

Attachment 4: Imazamox International Residue Limit Status Sheet.

cc: L. Venkateshwara (RAB1), W. Wassell (RAB1), 

RDI: RAB1 (6/5/14), C. Smith (6/5/14)

L. Venkateshwara: S10956: PY-S :( 703)308-2722:7509P:RAB1
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Attachment 1: Imazamox Identity and Physicochemical Properties.

Chemical Identity of Imazamox.

Nomenclature.

Imazamox

Chemical structure

Common name Imazamox

IUPAC nomenclature 2-[(RS)-4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl]-5-

methoxymethylnicotinic acid

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

(methoxymethyl)-3-pyridinecarboxylic acid

CAS registry number 114311-32-9

Physical/Chemical Characteristics of Imazamox.

Physicochemical Properties of Imazamox.

Parameter Value Reference

Melting range 166.0-166.7oC Memo, 12/09/94, R. Cook, 

pH 2.35; 1% aqueous suspension (w:v) D203639

at 24.5°C

Density (g/mL) 0.423 g/mL tapped bulk density at 

24.5°C 

0.304 g/mL untapped bulk density 

at 24.5°C

Water solubility (ppm) 4413 ppm (deionized water at 

20°C)

114,000 ppm (pH 5 buffer)

>643,000 ppm (pH 7 buffer)

>652,000 ppm (pH 9 buffer)

Solvent solubility (g/100mL) hexane: 0.0006

methanol: 6.68

acetonitrile: 1.85

toluene: 0.21

acetone: 2.93

dichloromethane: 14.3

ethyl acetate: 1.02

Vapor pressure <1.0 x 10-7torr at 25° C

Dissociation constant, pKa 2.3 and 3.3 at low to medium pH 

(0.5-6) and 10.8 at high pH (9-13)

Octanol/water partition coefficient Kow = 5.36 at pH 5 and 6 and 25 C

UV/visible absorption spectrum Not Available
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Attachment 2: Imazamox Acute, Subchronic, and Chronic Toxicity Profile

Acute Toxicity Profile- Imazamox Technical.

Guideline

No. Study Type MRID # Results Toxicity Category

870.1100 Acute Oral 43193207 LD50 5,000 mg/kg

(limit dose)

IV

870.1200 Acute Dermal 43193208 LD50 4,000 mg/kg

(twice the limit dose)

III

870.1300 Acute Inhalation 43193209 LD50 6.3 mg/L IV

870.2400 Primary Eye Irritation 43193210 Moderately irritating III

870.2500 Primary Skin Irritation 43193211 Not an irritant IV

870.2600 Dermal Sensitization 43193212 Not a skin sensitizer N/A

Subchronic, Chronic, or Other Toxicity Profile of Imazamox.

Guideline No./ 

Study Type

MRID No. (year)/

Classification /Doses Results

870.3100

90-Day oral toxicity 

rodents-rat

43193219 (1992)

Acceptable/guideline

0; 1,000; 10,000; or 20,000 ppm

0; 81; 833; or 1,661 mg/kg/day

NOAEL = >1,661 mg/kg/day (HDT).

LOAEL = not observed.

870.3150

90-Day oral toxicity 

nonrodents-dog

43193220 (1994)

Acceptable/guideline

0; 1,000; 10,000; or 40,000 ppm

0; 34; 329; or 1333 mg/kg/day

NOAEL = >1,333 mg/kg/day (HDT).

LOAEL = not observed.

870.3200

28-Day dermal 

toxicity-rat

43876213 (1995)

Acceptable/guideline

0; 250; 500; or 1000 mg/kg/day

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

LOAEL = not observed.

870.3700a

Prenatal 

developmental in 

rodents- rat

43193221 (1994)

Acceptable/guideline

0; 100; 500; or 1000 mg/kg/day

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

LOAEL = not observed.

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

LOAEL = not observed.

870.3700b Prenatal 

developmental in 

nonrodents- rabbit

43876216 (1995)

Acceptable/guideline

0; 300; 600; or 900 mg/kg/day

Maternal: NOAEL = >900 mg/kg/day (HDT).

LOAEL = not observed.

Developmental: NOAEL = >900 mg/kg/day (HDT).

LOAEL = not observed.

870.3800 

Reproduction and 

fertility effects- rat

43876217 (1995)

Acceptable/guideline

0; 1,000; 10,000; or 20,000 ppm

73; 748; or 1469 mg/kg/day for 

males and 88; 892; or 1705 

mg/kg/day for females

Parental/Systemic NOAEL = >1,705 mg/kg/day 

(HDT).

LOAEL = not observed.

Reproductive NOAEL = >1,705 mg/kg/day (HDT).

LOAEL = not observed.

Offspring NOAEL = >1,705 mg/kg/day (HDT).

LOAEL = not observed.

870.4100b Chronic 

toxicity- dog

43876214 (1995)

Acceptable/guideline

0; 1,000; 10,000; or 40,000 ppm

0; 9.5; 282.5; or 1165 mg/kg/day

NOAEL = 1,165 mg/kg/day (HDT).

LOAEL = not observed.

870.4300 Chronic/

Carcinogenicity- rat

43891001 (1995)

Acceptable/guideline

0; 1,000; 10,000; or 20,000 ppm

0; 52; 528; or 1,068 mg/kg/day

NOAEL = 1,068 mg/kg/day (HDT).

LOAEL = not observed.

No evidence of carcinogenicity at doses tested.
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Subchronic, Chronic, or Other Toxicity Profile of Imazamox.

Guideline No./ 

Study Type

MRID No. (year)/

Classification /Doses Results

870.4300 

Carcinogenicitymouse

43876215 (1995)

Acceptable/guideline

0; 500; 3,500; or 7,000 ppm

73; 535; or 1,053 mg/kg/day for 

males and 96; 664; or 1,348 

mg/kg/day for females

NOAEL = 1,348 mg/kg/day (HDT, females).

No evidence of carcinogenicity at doses tested.

870.5100 Gene 

Mutation

43193222 (1994)

Acceptable/guideline

0; 100; 500; 1,000; 2,500; or 

5,000 μg/plate

Non-mutagenic when tested up to 5,000 ug/plate, in 

presence and absence of metabolic activation, in S. 

typhimurium strains A1535, TA1538, TA98, TA100

and E.coli strain WP2uvra.

870.5300 Gene 

Mutation

43193223 (1993)

Acceptable/guideline

50; 100; 500; 1,000; 2,000; or 

4,000 μg/mL 

There was no indication that imazamox, tested up to 

insoluble levels, induced a mutagenic response in the 

presence or absence of S9 activation.

870.5375 

Chromosome 

aberration

43193224 (1993)

Acceptable/guideline

1,250; 2,500; or 5000 mg/kg

Non mutagenic; no significant increase in the 

frequency of micronucleated polychromatic 

erythrocytes in bone marrow cells were seen.

870.5375 

Chromosome 

aberration

43193225 (1994)

Acceptable/guideline

833; 1,667; or 3,333 μg/mL both 

in the presence of Aroclor 1254-

induced rat liver activation

No indication that imazamox, tested up to insoluble 

levels, induced a clastogenic response in the presence 

or absence of S9 activation. 

870.7485 

Metabolism and 

pharmacokinetics –

rat

43876218 (1995)

single intravenous dose at 10 

mg/kg body weight or orally by 

gavage as a single dose at 10 or 

1,000 mg/kg or as a single oral 

dose at 10 mg/kg following a 14-

day pretreatment with unlabeled 

imazamox at 10 mg/kg

[

14C]AC 299,263 was readily absorbed by male and 

female rats following intravenous or oral dosing; >73% 

of the administered dose was excreted in the urine 

within 24 hours of dosing. Pretreatment and dose level 

had little effect on the proportion of dose eliminated in 

urine from the oral dose groups. The rate of urinary 

excretion for the low and high oral dose groups was 

lower (74.0-82.0%) than the intravenous groups (84.5-

91.2%), suggesting a lack of complete absorption of the 

test substance. Within 168 hours of dosing at 10 mg/kg 

(with or without pretreatment) or 1,000 mg/kg, 88.0-

99.3% of the administered dose was recovered from 

both sexes, of which 74.0-91.2% was in the urine. 

Fecal excretion comprised 1.9-2.7% of the 

administered dose in the intravenous groups, compared 

to 12.2-24.2% in all oral dose groups. Organic 

volatiles were not expected to form (not measured). 

Total [14C]AC 299,263 equivalents in tissues accounted 

for <0.007% of the actual administered dose for all 

treatment groups.
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Attachment 3: Summary of Occupational and Residential Registered Uses 

Registration 

Number and 

Product Name

Crop/Use Site

Formulation

and Percent 

Active 

Ingredient

Application 

method

Maximum 

App Rate (lb 

ai/A)

REI

241-378

Imazamox Herbicide 

Technical

Alfalfa, chicory, 

CLEARFIELD® 

canola, 

CLEARFIELD®

rice, 

CLEARFIELD®, 

sunflowers, 

CLAERFIELD®

wheat, clover grown 

for seed, edible 

legumes and 

soybeans

97.4% N/A N/A N/A

241-379

Raptor® Herbicide

Alfalfa, beans (dry), 

chicory, clover 

grown for seed, 

edamame, lima bean 

(succulent), Peas 

(dry), pea (English), 

snap bean and 

soybean

Liquid, 

12.1%

aerial, 

ground, (no 

chemigation)

0.047 lb ae/A 4 hours

241-380

RAPTOR® TM DG 

Herbicide

Soybeans WSP

70%

aerial, 

ground, (no 

chemigation)

0.91 lb ai/A 4 hours

241-437

CLEARCAST®

Herbicide

Control of 

vegetation in and 

around aquatic and 

noncropland sites 

including areas that 

may be grazed or cut 

for hay

Liquid

12.1%

aerial, 

ground, (no 

chemigation)

Not specified Not 

specified

241-439

CLEARCAST®

2.7G Herbicide

Control of 

vegetation in aquatic 

sites

Granular

2.7%

aerial and 

drawdown 

application

Not specified Not 

specified

241-441 

Beyond® Clearfield®

Production System 

Herbicide

For use only on 

Clearfield® canola, 

Clearfield lentil, 

Clearfield rice, 

Clearfield and 

Clearfield®Plus 

sunflower, and 

Clearfield and 

Clearfield®Plus 

Wheat

Liquid

12.1%

aerial, 

ground, (no 

chemigation)

0.062 lb ae/A 4 hours

7969-238

CLEARMAX® Clearfield® wheat Liquid12.1%

aerial, 

ground, (no 

chemigation)

Not Specified 12 hours
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Attachment 4: Imazamox International Residue Limit Status Sheet.

International Residue Limits 

Imazamox (PC Code; 02/26/14)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

40 CFR 180.1223 exemption from the 

requirement of a tolerance.

The herbicide imazamox, (±) 2, -[4,5-dihydro4-methyl-4-(1-methylethyl)-5-oxo-1Himidazol-2-yl]-5-(methoxymethyl)-3-

pyridinecarboxylic acid, is exempt from the 

requirement of a tolerance on all food 

commodities when applied as a herbicide in 

accordance with good agricultural practices.

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

methylethyl)-5-oxo-1H

-imidazol-2-yl]-5-

(methoxymethyl)-3-

pyridinecarboxylic

acid

None

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

US Canada Mexico1 Codex

0.05 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, rapeseeds (canola), sesame 

seeds, sweet rocket seeds

0.05 Dry (adzuki beans, beans, blackeyed peas, broad 

beans, catjang seeds, chickpeas, cowpea seed, guar 

seeds, kidney beans, lablab beans, lentils, lima beans, 

moth beans, mung beans, navy beans, pink beans, pinto 

beans, rice beans, southern peas, tepary beans, urd 

beans); grain lupin

0.25 dry lentils

0.1 Dry soybeans

0.01 Eggs

0.05 fenugreek seeds

0.01 Meat byproducts of (cattle, goats, horses, poultry, 

sheep)

0.01 Meat of (cattle, goats, horses, poultry, sheep)

0.01 Milk

0.05 Peas 

0.3 sunflower seeds

0.05 wheat

Completed: M. Negussie; 02/27/14

1 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.