UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: June 6, 2014 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Imazaquin. Human Health Risk Assessment Scoping Document in Support of 

Registration Review. 

PC Codes: 128848 (imazaquin), DP Barcode: 418729 

128840 (ammonium salt of 

imazaquin) 

Decision No.: 488888 Registration Nos.: NA 

Petition No.: NA Regulatory Action: Registration Review 

Case No.: 7204 Risk Assessment Type Scoping Document 

TXRNo.: NA CAS No.: 81335-37-7; 81335-47-9 

MRIDNo.: NA 40 CFR: § I 80.426 

FROM: Danette Drew, Chemist 

Seyed Tadayon, Chemist ~ , , 

John 

Risk Assessmen

Liccione, Ph.D.

t Branches 

, Toxico 

V and 

ogist 

I 

~ 

Health Effects Division (7509P) 

THRU: MichaelS. Metzger, Branch Chief t J ~ J A 

Risk Assessment Branches v and vrD·'\ v..{;.-

Health Effects Division (7509P) 

TO: Wilhelmena Livingston, Chemical Review Manager 

Risk Management and Implementation Branch 4 

Pesticide Re-evaluation Division (7508P) 

Attached is the Health Effects Division's (HED) human health risk assessment scoping document 

for imazaquin in support of the registration review process. 

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Page 2 of 22

EXECUTIVE SUMMARY

HED has evaluated the available data and the most recent human health risk assessments for

imazaquin to determine the scope of work necessary to support the registration review process. 

HED has considered the currently labeled use patterns, as well as the available toxicity and 

exposure information. The most recent HED human health risk assessment for imazaquin was 

completed in October 2005 (S. Stanton, 10/31/2005, D302939, Imazaquin and its Salts: HED 

Chapter of the Tolerance Reassessment Eligibility Decision (TRED) Document) for inclusion in the 

Report of the Food Quality Protection Act (FQPA) Tolerance Reassessment Progress and Risk 

Management Decision (TRED) for Imazaquin which was issued in December 2005.

Imazaquin (imazaquin [± - 2-(4,5-Dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl)-

3- quinolinecarboxylic acid] is an imidazolinone herbicide which controls weeds by inhibiting the 

synthesis of specific amino acids (valine, leucine and isoleucine) necessary for plant growth.

Imazaquin is formulated as an acid or ammonium salt. It is registered as a pre-plant, preemergence and early post-emergence herbicide for use on soybeans. It is also registered for preand post-emergence weed control on ornamentals and warm season turfgrass in both residential 

(lawns) and non-residential (golf courses) settings.

The toxicology database for imazaquin is complete. The studies that are required in accordance 

with the 2007 revised 40CFR Part 158 Toxicology Data requirements for subchronic inhalation, 

acute neurotoxicity (ACN), subchronic neurotoxicity (SCN) and immunotoxicity have not been 

submitted for imazaquin. However, HED’s Hazard and Science Policy Council (HASPOC; TXR 

0056978; 5/22/14) has determined that, based on a weight of evidence (WOE) approach

considering all the available hazard and exposure information for imazaquin and other 

imidazolinone chemicals, those studies may be waived for imazaquin.

The toxicology studies with imazaquin indicate that the most commonly observed clinical sign in

the chronic studies (mice and dogs) was decreased body weight. The toxicity point of departure

selected for chronic dietary oral, short-term incidental oral, and short-term and intermediate-term 

dermal and inhalation exposures was based on weight loss, slight anemia, evidence of skeletal

muscle myopathy and supporting hematology and clinical chemistry differences seen in the chronic 

dog study. There was no endpoint attributable to a single dose, so an acute point of departure was 

not determined. There was no evidence of neurotoxicity, carcinogenicity, genotoxicity, or 

mutagenicity. There was no qualitative or quantitative susceptibility of the developing fetus or 

offspring, based on results from the developmental and reproductive toxicity studies. Based on the 

completeness of the database, the lack of susceptibility, the lack of neurotoxicity, and the 

conservative nature of the exposure assessment, HED previously recommended that the required 

10x Food Quality Protection Act (FQPA) Safety Factor be reduced to 1x.

The residue chemistry database for imazaquin is complete, and no additional data are needed. The 

residue of concern (in plants and livestock) for tolerance enforcement and risk assessment is parent 

compound (imazaquin). The residue of concern for ground water based drinking water is 

imazaquin, and for surface water based drinking water is imazaquin plus its photolytic degradates. 

A tolerance has been established under 40 CFR §180.426 for residues of imazaquin in soybean. 
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The current tolerance expression should be updated to comply with HED’s current policy on 

tolerance expressions. There are currently no international maximum residue limits (MRLs) for 

imazaquin, so there are no harmonization issues with Codex, Canada, or Mexico. 

The dietary exposure database is adequate. The previous chronic dietary assessment was very 

conservative (100% crop treated, tolerance level residues, and drinking water concentrations based 

on high-end modeling) and did not result in risk estimates of concern (dietary risk estimates were 

less than 1% of the cPAD). At this time, a revised dietary risk assessment is not anticipated for 

imazaquin, provided there are no significant changes to the toxicological points of departure and 

uncertainty factors and there are no significant changes to EPA’s Environmental Fate and Effect 

Division’s (EFED’s) estimated drinking water concentrations(EDWCs) .EFED has indicated that they 

will be updating the drinking water assessment under registration review.

There were no residential handler or post-application risk estimates of concern identified in the 

2005 assessments for the home turf use, nor were there risk estimates of concern for the postapplication exposures to treated golf courses. A revised residential exposure assessment using the 

2012 Residential SOPs will be needed during registration review. Any revisions to toxicological 

PODs or uncertainty factors will be incorporated. EPA is now requiring chemical specific TTR 

data for imazaquin, since the screening estimate for residential turf post-application exposure using

the 2012 SOPs and default turf transferable residue (TTR) values for imazaquin is not minimal in 

comparison to the level of concern (i.e., MOE is 130 compared to 1000 (ten times the level of 

concern) for children’s activities on treated turf). The required chemical specific TTR will also be 

considered for the revised post-application assessment.

In the 2005 risk assessment, HED provided chronic aggregate risk estimates for combined dietary 

(food and drinking water) exposures and short-term aggregate risk estimates from dietary and 

residential exposures combined. The aggregate risks were below HED’s level of concern. Revised 

aggregate risk assessments will be performed for imazaquin if there are any significant changes to 

toxicological PODs or uncertainty factors, if there are significant changes to residential exposures

and risk estimates (using the 2012 updated SOPs and any new TTR data), or if there are significant

changes to EFED’s EDWCs.

The occupational exposure database is adequate. An occupational exposure assessment was not 

performed for the 2005 imazaquin TRED. A screening assessment using current SOPs did not 

result in risk estimates of concern for handlers and post-application workers. Occupational handler

and post-application exposure assessments will be performed under registration review using 

current policies. Any changes to the toxicological PODs or uncertainty factors will also be 

incorporated.

Introduction

Imazaquin [± - 2-(4,5-Dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl)-3-

quinolinecarboxylic acid] is a broad spectrum, pre-plant, preemergence or postemergence

herbicide belonging to the imidazolinone class of pesticides. Imazaquin is currently formulated as 

an acid or ammonium salt; there are no current registrations for the sodium salt formulation. 
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Imazaquin is registered for food use on soybeans, as well as non-food use on warm season 

turfgrass and ornamentals in both residential and non-residential settings (including golf courses). 

Applications in residential settings may be made by both commercial applicators and homeowners. 

The registered imazaquin formulation types include water dispersible granule (WDG), wettable 

powder (WP), emulsifiable concentrate (EC) and soluble concentrate (SC). 

The nomenclature and physiochemical properties of imazaquin can be found in Attachment 1.

Hazard Identification/Toxicology

The toxicology database for imazaquin is considered complete and includes the following studies: 

21-day dermal toxicity study in the rabbit, subchronic oral toxicity in the rat, chronic oral toxicity 

in the dog, chronic toxicity/carcinogenicity in the rat, carcinogenicity in the mouse, prenatal 

developmental toxicity in the rat and rabbit, reproductive toxicity in the rat and rabbit, metabolism 

in the rat and a special thyroid study in the rat. In addition, there is a complete battery of 

genotoxicity studies. 

The subchronic inhalation study, acute neurotoxicity study (ACN), subchronic neurotoxicity study 

(SCN), and immunotoxicity study, now required in accordance with new data requirements for

conventional pesticide registration (40 CFR Part 158), have not been submitted for imazaquin. 

HED’s Hazard and Science Policy Council (HASPOC; TXR 0056978) recently met (5/22/14) and

determined that, based on a weight of evidence (WOE) approach considering all the available 

hazard and exposure information for imazaquin and other imidazolinone chemicals, those studies 

are may be waived and that the use of the current oral study POD is protective for assessing 

exposures to imazaquin.

Overall, imazaquin causes subchronic and chronic toxicity at relatively high doses, with few clinical

signs identified in rats, mice, dogs or rabbits. Toxicity was similar in both male and female test

animals, with the dog being the most sensitive species to imazaquin exposure. The most commonly

observed clinical sign in the chronic studies was decreased body weight, which was seen in both

mice and dogs. In the chronic dog study, additional effects were noted at the LOAEL of 125 

mg/kg/day, including slight anemia indicated by changes in hematology parameters, changes to

clinical chemistry and skeletal muscle myopathy at necropsy in both sexes. No effects were

observed at the highest dose tested (500 mg/kg/day) in the rat combined chronic toxicity/

carcinogenicity study; nor were systemic effects seen at the highest dose tested (1000 mg/kg/day) in

the rabbit 21-day dermal toxicity study.

The imazaquin database is considered adequate to characterize any potential pre- and/or post-natal 

risk to infants and children. In the developmental study in rats, treatment-related effects on fetal 

body weight and reduced ossification were observed, but only at the dose where maternal toxicity 

occurred. No treatment-related effects on fetuses were seen in the rabbit developmental toxicity 

study; and no toxicity in either the parents or offspring was noted at the highest dose tested in the 

rat reproductive study. Based on these studies, there is no indication of increased susceptibility of 

fetuses or offspring to imazaquin. Since there is no increased risk to infants and children and no 
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residual uncertainty in either the hazard or exposure assessments, the FQPA Safety Factor has been

reduced to 1X.

No evidence of neurotoxicity was observed in any of the available studies.

No evidence of carcinogenicity was seen in mice or rats, and imazaquin was non-mutagenic in 

available mutagenicity tests. Mice were dosed up to 600 mg/kg/day for 18 months, and rats were 

fed up to 500 mg/kg/day for 2 years without any evidence of a treatment-related increased 

incidence of tumors. Imazaquin was non-mutagenic in the Ames test and demonstrated negative 

responses in the in vitro cell transformation assay, a cytogenetics study with HGPRT in Chinese 

hamster cells and an unscheduled DNA synthesis assay.

Technical imazaquin has low (category III/IV) acute toxicity via the oral, dermal and inhalation

routes of exposure. It is non-irritating to the eye (category IV) and only mildly irritating to the skin.

Imazaquin did not cause dermal sensitization in the guinea pig.

Based on the use patterns and the submitted toxicology studies, HED previously selected endpoints 

for assessment of human health risk for chronic dietary exposure, residential incidental oral 

exposure, and occupational and residential inhalation and dermal exposures. For acute dietary 

exposure, an endpoint resulting from a single exposure was not identified. As a result, an acute 

reference dose (aRfD) was not determined. A chronic reference dose (cRfD) of 0.25 mg/kg/day

was established for imazaquin, based on the NOAEL of 25 mg/kg/day in the dog chronic toxicity 

study and an uncertainty factor of 100 (10x for interspecies extrapolation and 10x for intraspecies 

variation). Effects seen at the LOAEL included body weight loss, clinical chemistry/hematology 

differences, slight anemia and skeletal muscle myopathy. Body weight decreases occurred in the 

first 4 weeks of the study; and the hematology data from the earliest assessment at 13 weeks 

indicated statistically significant changes in hematology parameters, raising concern that the anemia

effects of imazaquin may occur within a short or intermediate time frame. Therefore, the NOAEL 

of 25 mg/kg/day from this oral study was also selected to assess incidental oral, dermal and

inhalation exposures of short-, intermediate- and long-term duration. Although there was no toxic

effect of concern demonstrated in the rabbit 21-day dermal study at the limit dose (1000 

mg/kg/day), and there are no indications of developmental or reproductive toxicity or 

neurotoxicity, a dermal endpoint has been selected for imazaquin because effects noted in the 

chronic dog study suggest that the dog may be more sensitive to imazaquin than the rabbit, 

especially with regard to the induction of anemia. In the last risk assessment, a 50% dermal 

absorption factor was used based on comparison of the NOAEL of 1000 mg/kg/day from the rabbit 

21-day dermal toxicity study (no LOAEL) with the maternal LOAEL of 500 mg/kg/day for body 

weight effects in the rabbit oral prenatal developmental toxicity study.

See Attachment 2 for Toxicity Profile Tables and Attachment 3 for Toxicity Doses and Endpoints

Selection Table.

Conclusions: The toxicology database for imazaquin is complete. HED’s Hazard and Science 

Policy Council (HASPOC; TXR 0056978; 5/22/14) has determined that, based on a weight of 

evidence approach considering all the available hazard and exposure information for imazaquin 
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and other imidazolinone chemicals, the requirements for subchronic inhalation, acute neurotoxicity 

(ACN), subchronic neurotoxicity (SCN) and immunotoxicity studies may be waived. HED will reevaluate the toxicity endpoints, points of departure (PoDs) and uncertainty and other factors during 

registration review.

Residue Chemistry and Dietary Exposure

Residue Chemistry

The residue of concern for tolerance enforcement and risk assessment (plants and livestock) is the 

parent compound, imazaquin. A tolerance has been established under 40 CFR §180.426 for

residues of imazaquin in or on the raw commodity soybean at 0.05 ppm (method LOQ). There are 

no tolerances for residues of imazaquin on other livestock feed commodities of soybean, as there 

are enforceable grazing restrictions on the labels. Available data indicate that a Category 3

situation (40 CFR 180.6(a)3 “no reasonable expectation of finite residues”) exists with respect to 

residues of imazaquin in meat, meat by-products (mbyp), fat, and milk of cattle, goats, hogs, 

horses, and sheep; and in poultry meat, fat, mbyp, and eggs. There are currently no tolerances for 

imazaquin in livestock commodities. Existing analytical methods are considered adequate for both 

data collection and enforcement purposes.

The residue chemistry database for imazaquin is complete. The 2005 TRED identified the 

following two residue data requirements: provide storage durations for the soybean field trials

(860.1380), and submit multi-residue testing data for imazaquin (860.1360). The soybean storage 

durations and multi-residue testing data have since been submitted and reviewed (D. Soderberg, 

3/17/08, D346848, D346852; Imazaquin: BASF response to two data gaps noted in the TRED -

Determination of UV/Vis Absorption Spectra; and storage stability information regarding soybean 

field trials, and P.Savoia, 3/17/10, D370270, Imazaquin. Screening of Imazaquin through Food 

and Drug Administration (FDA) Multi-Residue Method Testing). The data requirements identified 

in the imazaquin TRED have been adequately fulfilled.

Dietary Exposure

Chronic dietary (food and drinking water) exposure assessments were previously conducted using 

the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database 

DEEM-FCID (D302943, Susan Stanton, 10/20/05). No acute dietary endpoint was identified for 

imazaquin; therefore, an acute dietary exposure assessment was not necessary. The food 

assumptions included that 100% of the soybean crop is treated and that residues of imazaquin are

present at the tolerance level of 0.05 ppm in all soybean food commodities. 

For water, EFED had provided a drinking water assessment (Drinking Water Assessment for 

Imazaquin and its Salts; K. Moore; June 21, 2005, as amended on September 27, 2005). Aqueous

photolysis is the only significant degradation pathway for imazaquin and leads to four major 

degradates greater than 10% of the applied amount of imazaquin (3-quinolinecarboxylic acid; 2,3 

quinolinedicarboxylic acid imide; 2,3 dihydro-3-imino-1H-pyrrolo-[3,4-b]quinoline-1-one; and 2,3 

quinolinedicarboxylic acid). These degradates are expected to form in surface water only. They 

are not expected to form in groundwater, since the parent compound is not exposed to light and 

aqueous photolysis does not occur. 
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HED had determined that the surface water degradates of imazaquin have the potential to be 

toxicologically equivalent to the parent compound; therefore, the residues of concern for risk 

assessment purposes in surface water include imazaquin and the following photolytic degradates:

3-quinolinecarboxylic acid; 2,3 quinolinedicarboxylic acid imide; 2,3 dihydro-3-imino-1H-pyrrolo-

[3,4-b]quinoline-1-one; and 2,3 quinolinedicarboxylic acid. The residue of concern in ground 

water is parent only.

Drinking water was incorporated directly into the dietary assessment using the tier 1 estimated

drinking water concentration (EDWC) for ground water generated by the SCI-GROW model (turf 

application scenario). The SCI-GROW groundwater estimate was selected for risk assessment

purposes, because this estimate of imazaquin only was higher than the PRZM-EXAMS model

estimates of imazaquin and its photolytic degradates in surface water.

All dietary (food and water) risk estimates were less than 1% of the chronic population-adjusted 

dose (cPAD) and were well below HED’s level of concern. 

Conclusions: The imazaquin residue chemistry database is complete and no new data are required. 

The previous (2005) dietary assessment included all registered food uses and was very 

conservative (100% crop treated, tolerance level residues, and drinking water concentrations based 

on high-end modeling) and did not result in risk estimates of concern (dietary risk estimates were 

less than 1% of the cPAD). At this time, a revised dietary risk assessment is not anticipated for 

imazaquin provided there are no changes to the toxicological points of departure and uncertainty or 

other factors, and there are no significant changes to EFED’s estimated drinking water

concentrations(EFED has indicated they will be updating the drinking water assessment under registration 

review).

Residential (Non-Occupational) Exposure

Imazaquin residential uses which may result in handler or post-application exposures include the 

use on lawns and recreational turf, such as golf courses. 

Residential Handler

Because imazaquin is not a restricted-use product (RUP) and a homeowner could potentially apply 

it in a residential setting, HED previously conducted a residential handler exposure assessment for 

home lawn uses (S.Tadayon, D302942, 10/6/2005, Imazaquin: Residential Exposure Assessment 

and Recommendations for the Tolerance Reassessment Eligibility Decision (TRED)). This handler 

exposure assessment was conducted using Health Effects Division Science Advisory Committee 

Policy 12: Recommended Revisions to The Standard Operating Procedures for Residential 

Exposure Assessment (2001). The short-term dermal and inhalation MOEs for handlers were much 

greater than the level of concern of 100 (MOEs ranged from 1,700 to 11,000) and were not of risk 

concern. HED’s Residential SOPs were revised in 2012. A residential handler exposure assessment 

using the revised residential SOPs will be performed during registration review. Revising the 

handler assessment using the updated SOPs is not expected to have a significant impact on the 
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previously calculated MOEs but will reflect more accurate exposure assumptions including 

updated body weights.

Residential Post-Application 

Residential post-application (dermal and incidental oral exposure) risk assessments were

previously conducted for children entering imazaquin-treated lawns. For adults, dermal exposures 

were assessed for lawn activities including turf mowing and for golfing (D302942, 10/6/2005). All 

of the short-term MOEs for these exposures were greater than 100 (MOEs ranged from 260 to 

1,000,000), and were not of risk concern. These assessments used the 2001 Residential SOPs. A

revised residential post-application exposure assessment using the updated 2012 Residential SOPs 

will be needed during registration review. 

Turf Transferable Residue: In accordance with the updated Part 158 data requirements (2007), a 

TTR study is required for occupational (e.g., sod farms, golf courses, parks, and recreational areas) 

or residential turf uses. As part of the recent revision to the Health Effects Division’s 2012 

Standard Operating Procedures for Residential Pesticide Exposure Assessment, HED analyzed all 

available data and selected new liquid and granular default values for the fraction of the application 

rate available for transfer after a turf application (FAR).1 These defaults are 1% for formulations 

applied as liquids (i.e., emulsifiable concentrates, liquids, wettable powders, dry flowables, etc.) 

and 0.2% for granular formulations. Of the available TTR studies submitted to the Agency, the 

maximum FAR value seen using a liquid product was 6.1% or 6.1 times higher than the default 

residue transfer value. The maximum FAR value seen in a TTR study using a granular product was 

0.69% or 3.5X the default residue transfer value. Therefore, for both liquid and granular 

formulations, a calculated MOE of approximately 10 times higher than the level of concern (e.g., 

an MOE > 1,000 if the LOC = 100) using the default residue transfer values would provide an 

adequate margin of safety for any potentially higher residues seen in a chemical specific TTR 

study (Guidance for Requiring/Waiving Turf Transferrable Residue (TTR) and Dislodgeable 

Foliar Residue (DFR) Studies. 12/12/2012, Exposure Science Advisory Council). TTR data are 

not available for imazaquin. HED has, for the purposes of this scoping exercise, completed 

screening level risk estimates based on the default TTR values. For the current uses of imazaquin, a 

chemical specific TTR study will be required for registration review since estimated MOEs for at 

least one residential post-application scenario is less than 1000 (i.e. screening dermal MOEs for 

activity on treated turf/lawns is 130 for children and 270 for adults). See Attachment 4.

Spray Drift

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

occur as a result of applications of imazaquin. The Agency is in the process of evaluating these 

types of exposures and might, as appropriate, develop policies and procedures to identify the need 

for and, subsequently, the way to incorporate these post-application exposures into the Agency’s 

risk assessments. 

The residential turf post-application assessment for imazaquin will provide a worst case estimate of 

potential exposure from spray drift. As the turf use rate is equal to or higher than agricultural 

 

1 http://www.epa.gov/pesticides/science/residential-exposure-sop.html
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application rates for imazaquin, this scenario is protective of any exposure of children via spray 

drift from agricultural imazaquin applications. The need for volatilization risk assessment for 

imazaquin will be examined during registration review.

Conclusions: There were no residential handler or post-application risks of concern identified in 

the 2005 imazaquin TRED. A revised residential exposure assessment using the 2012 Residential 

SOPs will be needed during registration review. Any revisions to toxicological PODs or 

uncertainty factors will be incorporated. Since the estimated residential turf post-application 

dermal exposure using default turf transferable residue (TTR) values for imazaquin is not minimal 

in comparison to the level of concern (i.e., MOE is 130 compared to 1000 (ten times the level of 

concern) for children’s activities on treated turf), EPA is now requiring TTR data for imazaquin.

The required chemical specific TTR will also be considered for the post-application assessment.

Aggregate Risk Assessment

In the 2005 risk assessment, HED provided chronic aggregate risk estimates for combined food 

and drinking water exposures; and short-term aggregate risk estimates from food, drinking water 

and residential (turf use) exposures combined. The short-term aggregate assessments included 

combining chronic exposure from drinking water with short-term incidental oral ingestion 

exposure in infant and children; and chronic exposure from drinking water with short-term 

inhalation exposure of adult residential handlers. The aggregate risk estimates were below HED’s 

level of concern.

Conclusions: The 2005 aggregate (food, water, and residential exposures) risk estimates were not 

of concern. Revised aggregate risk assessments will be performed for imazaquin if there are any 

changes to toxicological PODs or uncertainty factors, or if there are significant changes to the 

revised residential exposures (using the 2012 updated SOPs), or if there are significant changes to 

EFED’s EDWCs.

Occupational Exposure

An occupational exposure risk assessment was not performed for the 2005 imazaquin TRED.

HED has, for the purpose of this scoping exercise, conducted a screening level quantitative 

occupational exposure assessment for the soybean and turf uses (Attachment 5). There are no 

imazaquin specific data available for assessing occupational exposure and risk associated with 

registered products containing imazaquin. In the absence of chemical-specific data, HED has 

relied on information in the studies from Pesticide Handlers Exposure Database Version 1.1 

(PHED 1.1); the Agricultural Handler Exposure Task Force (AHETF) database; the ARTF 

database; or the Outdoor Residential Exposure Task Force (ORETF) database and standard 

assumptions with respect to the area treated and surrogate unit exposure data.

Occupational Handler

All occupational handler scenarios for the soybean use resulted in combined dermal and inhalation

MOEs that do not exceed HED's level of concern (MOEs ≥ 100) for short-term (ST) and
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intermediate-term (IT) exposure durations at label specified personal protective equipment (PPE). 

The soybean scenario combined MOEs ranged from 110 to 15,000, and the turf scenario combined 

MOEs ranged from 370 to 310,000 (Attachment 5).

Occupational Post-Application

Occupational post-application dermal exposure to imazaquin is possible for workers entering 

treated fields. HED’s screening level post-application assessment resulted in dermal MOEs ranging 

from 880 to 14,000, which do not exceed HED's level of concern (MOEs ≥ 100). 

Based on the occupational screening estimates, the current label restricted entry interval (REI) of 

12 hours is appropriate and in compliance Worker Protection Standard requirements. 

Conclusions: The occupational exposure database is adequate to support registration review of 

imazaquin. An occupational exposure assessment was not performed for the 2005 imazaquin 

TRED. A screening assessment using current SOPs did not result in risk estimates of concern. 

Occupational handler and post-application exposure assessments will be performed under 

registration review using current policies. Any changes to the toxicological PODs or uncertainty 

factors will also be incorporated.

Public Health and Pesticide Epidemiology Data

HED used OPP’s 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 to determine the 

number and severity of incidents that resulted from imazaquin exposure (S. Recore, D420257,

5/15/14, Imazaquin: Tier I Review of Human Incidents). For the Main IDS, from January 1, 2009 

to March 5, 2014, there were 0 incidents reported involving imazaquin in the database. In 

Aggregate IDS, from January 1, 2009 to March 5, 2014, there was 1 incident reported involving 

imazaquin in the database. This incident was classified as minor severity. The SENSOR-Pesticides 

1998-2010 query identified 0 cases involving imazaquin. Imazaquin is not included in the 

Agricultural Health Study (AHS); therefore, this study does not provide information for this report.

There does not appear to be a concern at this time that would warrant further investigation, since 

there was a low frequency of incidents involving imazaquin reported to IDS and SENSORPesticides. The Agency will continue to monitor the incident information and if a concern is 

triggered, additional analysis will be included in the risk assessment.

Tolerance Assessment and International Harmonization

Currently, the U.S. tolerance definition for imazaquin is expressed as “residues of the herbicide 2-

[4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl]-3-quinoline carboxylic acid.” 

The definition should be modified to read as follows (as per S. Knizner, 2009, Interim Guidance on 

Tolerance Expressions):
Page 11 of 22

Tolerances are established for residues of the herbicide imazaquin, including its metabolites and 

degradates, in or on the commodities in the table below. Compliance with the tolerance levels 

specified below is to be determined by measuring only imazaquin (2-[4,5-dihydro-4-methyl-4-(1-

methylethyl)-5-oxo-1H-imidazol-2-yl]-3-quinoline carboxylic acid).

There are currently no international maximum residue limits (MRLs) for imazaquin; therefore, 

there are no harmonization issues with Codex, Canada, or Mexico. See Attachment 6, International 

Maximum Residue Limits Table.

International or Intergovernmental Work Sharing

There is no current or forecasted work sharing efforts with other entities (e.g. California, Canada, 

EU, and OECD) for imazaquin.

Cumulative Risk Assessment

The Food Quality Protection Act (FQPA) requires the Agency to consider the cumulative risks of 

chemicals sharing a common mechanism of toxicity. EPA has not made a determination of

whether imazaquin has a common mechanism of toxicity with other substances. Therefore, a 

cumulative risk assessment has not been performed for imazaquin.

Data Requirements

Turf Transferable Residue (TTR) Study: 

There is a possibility for golfers and golf course maintenance workers to have post-application 

dermal exposure to imazaquin on treated turf. Based on the discussion in the residential sections of 

this document, a chemical specific TTR study will be required for imazaquin registration review 

since the estimated residential turf post-application dermal exposure using default TTR values is 

not minimal in comparison to the level of concern (LOC). Estimated dermal MOEs for turf postapplication scenarios are <1000 and the LOC is 100 (i.e. screening dermal MOEs for activity on 

treated turf/lawns is 130 for children and 270 for adults).

Attachments

Attachment 1. Chemical Identity

Attachment 2. Toxicity Profile Tables

Attachment 3. Toxicity Doses and Endpoints Selection Table

Attachment 4. Residential Post-Application Screening Estimates

Attachment 5. Occupational Handler Screening Estimates

Attachment 6. International Residue Limits Table 
Page 12 of 22

Attachment 1 

Chemical Identity: the chemical structure and physiochemical properties of imazaquin are found in 

Tables 1.1 and 1.2 below.

TABLE 1.1. Imazaquin and Imazaquin, Ammonium Salt Nomenclature

Chemical Structure

Common name Imazaquin

Molecular Formula C17H17N3O3

Molecular Weight 311.34

IUPAC name (RS)-2-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)quinoline-3-carboxylic acid

CAS name

± - 2-(4,5-Dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl)-3-

quinolinecarboxylic acid

CAS Registry Number 81335-37-7

PC Code 128848

Chemical Class Imidazolinone

Chemical structure

Common name Imazaquin, ammonium salt

IUPAC name (RS)-2-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)quinoline-3-carboxylic acid, 

monoammonium salt

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

quinolinecarboxylic acid, monoammonium salt

CAS # 81335-47-9

PC Code 128840
Page 13 of 22

TABLE 1 . 2 . Physicochemical Properties of Imazaquin

Parameter Value Reference

Melting point 219-224 °C (decomposes) MRID 00146197; PP#5F3273, 

RCB #1265, 1/9/86, A. Smith pH 4.6 at 25 °C

Density, bulk density, or specific gravity 0.39 g/mL untapped; 0.43 g/mL tapped

Water solubility at 25 °C 60 ppm

Solvent solubility g/100 mL

Acetone 0.30

DMF 6.80

DMSO 15.9

Ethanol 0.30

Heptane 0.02

Methanol 0.50

Methylene chloride 1.36

Toluene 0.04

Vapor pressure <2 x 10

-8 mm Hg at 45 °C

Dissociation constant, pKa 3.8

Octanol/water partition coefficient 2.2 at 22 °C

UV/visible absorption spectrum Not available
Page 14 of 22

Attachment 2

Toxicity Profile Tables

Table 2.1. Imazaquin Acute Toxicity Profile

Guideline

No. Study Type MRID(s) Results

Toxicity

Category

870.1100 Acute oral [rat] 00132576 LD50 = >5000 mg/kg IV

870.1200 Acute dermal [rabbit] 00132576 LD50 > 2000 mg/kg III

870.1300 Acute inhalation [rat] 00146199 > 5.5 mg/L (4 hours) III

870.2400 Acute eye irritation [rabbit] 00132576 Non-irritating IV

870.2500 Acute dermal irritation [rabbit] 00132576 Mildly irritating IV

870.2600 Skin sensitization [guinea pig] 00146200 Negative - not a sensitizer N/A
Page 15 of 22

 

Table 2 . 2 . Imazaquin S ubchronic, Chronic and Other Toxicity Profile

Guideline No./ 

Study Type

MRID No. (year)/ 

Classification /Doses Results

870.3100

90-Day oral 

toxicity (rat)

00131553 (1983) 

Acceptable/guideline

M&F: 0, 20, 80, 400 or 800 

mg/kg/day

0, 250, 1000, 5000 or 10,000 

ppm

NOAEL: 800 mg/kg/day

LOAEL: not established

870.3150

90-Day oral 

toxicity

No study. See chronic dog study below.

870.3200

21/28-Day dermal 

toxicity

(rabbit)

00146204 (1985) 

Acceptable/guideline 

M&F: 0, 250, 500 or 1000 

mg/kg/day

Systemic NOAEL = 1000 mg/kg/day

LOAEL = not established

Dermal NOAEL = 1000 mg/kg/day

LOAEL = Not established (no effects 

at highest dose tested)

870.3250

90-Day dermal 

toxicity

No study and not required.

870.3465

90-Day inhalation 

toxicity (species)

No study and not required.

870.3700a 

Prenatal 

developmental 

(rat)

00131552 (1983) 

Acceptable/guideline

0, 250, 500 or 2000 mg/kg/day

Maternal NOAEL = 500 mg/kg/day

LOAEL = 2000 mg/kg/day, based on 

salivation, alopecia, lethargy, 

flaccidity and 2/25 deaths

Developmental NOAEL = 500 mg/kg/day

LOAEL = 2000 mg/kg/day, based on 

slight decrease in fetal weight and 

reduced ossification.

870.3700b 

Prenatal 

developmental in 

(rabbit)

00147011 (1984) 

Acceptable/guideline

0, 100, 250, or 500 mg/kg/day

Maternal NOAEL = 250 mg/kg/day

LOAEL = 500 mg/kg/day based on 

decreased weight gain.

Developmental NOAEL = 500 mg/kg/day (no effects 

seen at highest dose)

LOAEL = not identified
Page 16 of 22

Table 2.2 Subchronic, Chronic and Other Toxicity Profile - Imazaquin

Guideline No./ 

Study Type

MRID No. (year)/ 

Classification /Doses

Results

870.3800

Reproduction and 

fertility effects 

(rat)

00147016 (1985) 

Acceptable/guideline

0, 92-97, 431-483 or 870-938 

mg/kg/day (M)

0, 99-108, 498-525 or 947-1051 

mg/kg/day (F)

0, 1000, 5000 or 10,000 ppm

(M and F)

Parental/Systemic

NOAEL = 870-938 mg/kg/day (M)

= 947-1051 mg/kg/day (F) 

LOAEL = not identified

Reproductive NOAEL = 870-938 mg/kg/day (M)

= 947-1051 mg/kg/day (F) 

LOAEL = not identified

Offspring NOAEL = 870-938 mg/kg/day (M)

= 947-1051 mg/kg/day (F) 

LOAEL = not identified

870.4100b 

Chronic toxicity 

(dog)

00138972 (1984) 

Acceptable/guideline

M&F: 0, 5, 25 or 125 mg/kg/day

0, 200, 1000 or 5000 ppm

NOAEL = 25 mg/kg/day

LOAEL = 125 mg/kg/day, based on decreased body 

weight gain, skeletal muscle myopathy, elevated clinical 

chemistry values (ALT, AST, LDH, CPK) and decreased 

hematology values (RBC, Hgb, Hct, MCV and MCH)

870.4200

Carcinogenicity

(rat)

See combined toxicity/carcinogenicity study in rats below

870.4300

Carcinogenicity

(mouse)

00146206 (1985) 

Acceptable/guideline 

M&F: 0, 38, 150 or 600 

mg/kg/day

(estimated by calculation)

0, 250, 1000 or 4000 ppm

NOAEL = 150 mg/kg/day (MF)

LOAEL = 600 mg/kg/day, based on decreased body 

weight gain in females and males

no evidence of carcinogenicity in mice

870.4300

Combined chronic 

toxicity/carcinoge 

nicity (rat)

00146205 (1985) 

Acceptable/guideline 

M&F: 0, 50, 250 or 500 

mg/kg/day

0, 1000, 5000 or 10,000 ppm

NOAEL = 500 mg/kg/day (no effects at highest dose 

tested).

LOAEL = not identified

no evidence of carcinogenicity in rats

Gene Mutation

870.5100 

(Ames test)

00131549 

(1982) 

Minimum

Non-mutagenic

Cytogenetics

870.5300

(in-vitro cell 

transformation)

00147018 (1984) 

Acceptable

Negative

Cytogenetics

870.5375 

(HGPRT in 

Chinese hamster)

00147017 (1985) 

Acceptable

Negative
Page 17 of 22

Table 2 . 2 Subchronic, Chronic and Other Toxicity Profile - Imazaquin

Guideline No./ 

Study Type

MRID No. (year)/ 

Classification /Doses

Results

Other mechanism

870.5550 

(unscheduled 

DNA synthesis)

00147019 (1984) 

Acceptable/guideline

Negative

870.6200a Acute 

neurotoxicity 

screening battery

No study and not required.

870.6200b 

Subchronic 

neurotoxicity 

screening battery

No study and not required.

870.6300

Developmental 

neurotoxicity

No study and not required.

870.7485

Metabolism and 

pharmacokinetics 

(rat)

00131550 (1983) 

Acceptable/Nonguideline

0 or 12 mg/kg

94% recovered in urine and 3.94% in the feces with

3.75% recovered in the cage washings. Total recovery

- 102%. Only parent (99.7%) was detected in the 

urine.

870.7600

Dermal 

penetration

No study and not required.

Special studies

90-day thyroid 

function (rats)

42054601- (1991) 

Acceptable/Nonguideline

0, 100 and 5000 ppm or 4.98 

and 245.4 mg/kg/day.

NOAEL = 4.98 mg/kg/day

LOAEL = 245.4 mg/kg/day, based on slight decrease in 

body weight with a 20% decrease in body weight gain 

and increase in TSH (up to 2 fold) accompanied by a 

decrease in serum total T4 and a slight decrease in 

serumT3.
Page 18 of 22

Attachment 3

Imazaquin Endpoints and Doses for Risk Assessment

Table 3.1 Summary of Toxicological Doses and Endpoints for Imazaquin for Use in Dietary and NonOccupational Human Health Risk Assessments

Exposure

Scenario

Dose Used in Risk

Assessment, UF

Special FQPA SF* and 

Level of Concern for 

Risk Assessment

Study and Toxicological Effects

Acute Dietary

(females 13-49)

Not Applicable Not Applicable No appropriate acute endpoint 

identified for this population (i.e., no 

toxic effect attributable to a single dose

identified).

Acute Dietary 

(general)

population)

Not Applicable Not Applicable No appropriate acute endpoint 

identified for this population (i.e., no 

toxic effect attributable to a single dose

identified). Chronic Dietary

(all populations)

NOAEL = 25 

mg/kg/day

UF = 100 

cRfD = 0.25

FQPA SF = 1 X

cPAD = cRfD 

FQPA SF

cPAD = 0.25 mg/kg/day

Chronic toxicity - dog

LOAEL = 125 mg/kg/day, based on 

weight loss, slight anemia, evidence of

skeletal muscle myopathy and 

supporting hematology/clinical 

chemistry differences

Incidental Oral -

all durations.

NOAEL = 25 

mg/kg/day

FQPA SF = 1 X

MOE of concern = 100 

(Residential and 

Occupational)

Same as above.

Dermal -

all durations.

NOAEL = 25 

mg/kg/day

FQPA SF = 1 X

MOE of concern = 100 

(Residential and 

Occupational)

Assume 50% dermal 

absorption.

Same as above.

Inhalation -

all durations

NOAEL = 25 

mg/kg/day

FQPA SF = 1X

MOE of concern = 100 

(Residential and 

Occupational)

Assume 100%

absorption.

Same as above.

Cancer (oral, 

dermal, inhalation)

Classification: No evidence of carcinogenicity in mice or rats.

UF = uncertainty factor, FQPA SF = FQPA safety factor, NOAEL = no observed adverse effect level,

LOAEL = lowest observed adverse effect level, PAD = population adjusted dose (a = acute, c = chronic) RfD =

reference dose, MOE = margin of exposure
Page 19 of 22

Attachment 4

Residential Post-Application Screening Estimates

Table 4.1 Short-Term Residential Post-application Exposure and Risk Estimates for Imazaquin

Lifestage Post-application Exposure Scenario Dose (mg/kg/day) MOEs

Liquid formulation

Adult

Turf

Liquid 

formulation

1.0 lb ai/A

Dermal

Physical Activities on Turf 0.09 270

Mowing 0.0019 13,000

Golfing 0.0074 3,400

Child 11 < 16 

years old Dermal Mowing 0.0022 11,000

Golfing 0.0086 2,900

Child 6 < 11 years 

old Dermal Golfing

Child 1 < 2 year 

old

Dermal Physical Activities on Turf 0.19 130

Hand to Mouth 0.0038 6,600

Object to Mouth 0.00012 220,000

Short- and Intermediate-term Incidental Soil 

Ingestion 0.0000085 3,000,000
Page 20 of 22

Attachment 5 

Occupational Handler Screening Estimates

Table 5.1 Occupational Handler ST and IT Exposure and Risk Estimates for Imazaquin 

Exposure 

Scenario Crop or Target

Dermal Unit 

Exposure 

(μg/lb ai)1

Inhalation Unit 

Exposure 

(μg/lb ai)1 Maximum 

Application 

Rate (lb 

ai/A)2

Area 

Treated 

(acres)3

Dermal

(LOC = 100)

Inhalation

(LOC = 100)

Total

(LOC = 

100)

Mitigation Level 

= baseline unless 

indicated 

otherwise

Mitigation Level 

= baseline unless 

indicated 

otherwise

Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day)6 MOE7 MOE8

Mixer/Loader (WDG/DF)

Aerial Field crop, high-acreage

(soybeans)

227 8.96

0.125

1200 0.213 120 0.0168 1500 110

Chemigation Field crop, high-acreage(soybeans) 350 0.0621 400 0.0049 5,100 370

Groundboom

Golf course (tees and greens only)

0.5

5 0.00355 7,000 0.00028 89,000 6,500

Golf course (fairways, tees, greens) 40 0.0284 880 0.00224 11,000 810

Field crop, high-acreage(soybeans) 0.125 200 0.0355 700 0.0028 8,900 650

Mixer/Loader (L/SC/EC)

Aerial Field crop, high-acreage(soybeans)

220 0.219

0.125

1200 0.206 120 0.000411 61,000 120

Chemigation Field crop, high-acreage(soybeans) 350 0.0602 420 0.00012 210,000 420

Groundboom

Golf course (tees and greens only) 0.5 5 0.00344 7,300 0.00000685 3,600,000 7,300

Golf course (fairways, tees, greens) 0.5 40 0.0275 910 0.0000548 460,000 910

Field crop, high-acreage(soybeans) 0.125 200 0.0344 730 0.0000685 360,000 730

Mixer/Loader (WP in soluble packages)

Aerial Field crop, high-acreage(soybeans)

9.8

(Engineering 

Control)

0.24

(Engineering 

Control)

0.125

1200 0.00919 2700 0.00045 56000 2600

Chemigation Field crop, high-acreage(soybeans) 350 0.00268 9,300 0.000131 190,000 8,900

Groundboom

Golf course (tees and greens only) 0.5 5 0.0000769 330,000 0.00000375 6,700,000 310,000

Golf course (fairways, tees, greens) 0.5 40 0.000613 41,000 0.00003 830,000 39,000

Field crop, high-acreage(soybeans) 0.125 200 0.00153 16,000 0.000075 330,000 15,000
Page 21 of 22

Table 5.1 Occupational Handler ST and IT Exposure and Risk Estimates for Imazaquin 

Exposure 

Scenario Crop or Target

Dermal Unit 

Exposure 

(μg/lb ai)1

Inhalation Unit 

Exposure 

(μg/lb ai)1 Maximum 

Application 

Rate (lb 

ai/A)2

Area 

Treated 

(acres)3

Dermal

(LOC = 100)

Inhalation

(LOC = 100)

Total

(LOC = 

100)

Mitigation Level 

= baseline unless 

indicated 

otherwise

Mitigation Level 

= baseline unless 

indicated 

otherwise

Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day)6 MOE7 MOE8

Applicator

Aerial Field crop, high-acreage(soybeans)

5

(Engineering 

Control)

0.068

(Engineering 

Control)

0.125

1200 0.00469 5,300 0.000128 200,000 5200

Groundboom

Golf course (tees and greens only)

78.6 0.34

5

0.000307

81,000 0.00000266 9,400,000 80,000

Golf course (fairways, tees, greens) 40 0.00246 10,000 0.0000213 1,200,000 9,900

Field crop, high-acreage(soybeans) 200 0.0123 2,000 0.000106 240,000 2,000

Flagger

Flagger All crops 11 0.35 0.125 350 0.00301 8,300 0.000191 130,000 7,800

Mixer/Loader/Applicator(WDG/DF)

Mechanicallypressurized 

Handgun

Golf course (tees and greens only) 1960 42 0.25 5 0.0306 820 0.00131 19,000 790

Golf course (fairways, tees, greens)

Mixer/Loader/Applicator(LC/SC/EC)

Mechanicallypressurized 

Handgun

Golf course (tees and greens only)

1140 1.9 0.25 5 0.0178 1,400 0.0000594 420,000 1400 Golf course (fairways, tees, greens)

Mixer/Loader/Applicator(WP in soluble packages

Mechanicallypressurized 

Handgun

Golf course (tees and greens only) 1350 18 0.25 5 0.0211 1,200 0.000563 44,000 1200

Golf course (fairways, tees, greens)

Bolded MOEs are below the LOC of 100.

1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2013); Level of mitigation: Baseline, Eng. Controls.

2 Based on registered and proposed labels.

3 Exposure Science Advisory Council Policy #9.1 and Registrant information.

4 Dermal Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre) × Area Treated (A/day) ÷ BW (80 kg).

5 Dermal MOE = Dermal NOAEL (25 mg/kg/day) ÷ Dermal Dose (mg/kg/day).

6 Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre) × Area Treated (A/day) ÷ BW (80 kg).

7 Inhalation MOE = Inhalation NOAEL 25 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).

8 Total MOE = 1 ÷ (1/Dermal MOE) + (1/Inhalation MOE).
Page 22 of 22

Attachment 6

International Maximum Residue Limits 

Table 6.1. Summary of US and International Tolerances and Maximum Residue Limits for 

Imazaquin

Residue Definition:

US Canada Mexico1 Codex

40 CFR 180.426

A tolerance is established for residues of the 

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

methylethyl)-5-oxo-1H-imidazol-2-yl]-3-

quinoline carboxylic acid

None None

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

US Canada Mexico1 Codex

Soybean 0.05

Completed by: M. Negussie; 02/19/14

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