UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF

CHEMICAL SAFETY AND

POLLUTION PREVENTION

MEMORANDUM

Sept. 30, 2013 

SUBJECT: Quinclorac: Risk Assessment to Support Permanent Tolerance for Rapeseed 

Subgroup 20A Without U.S. Registration. 

PC Code: 128974, 028974 DP Barcode: D406420

Decision No.: 464830 Registration No.: NA

Petition No.: 2E8035 Regulatory Action: Tolerance, No Registration

Risk Assessment Type: Single Chemical/ 

Aggregate

Case No.: 7222

TXR No.: NA CAS No.: 84087-01-4, 84087-48-9

MRID No.: NA 40 CFR: 180.463

FROM: Susan V. Hummel, Risk Assessor

Abdallah Khasawinah, Ph.D., Toxicologist

Bonnie Cropp-Kohlligian, Chemistry and Dietary Exposure Assessor

Risk Assessment Branch IV, Health Effects Division (7509P)

THROUGH: Elissa Reaves, Ph.D., Acting Branch Chief

Risk Assessment Branch IV

Health Effects Division (7509P)

TO: Maggie Rudick and Kable Davis, PM25

 Herbicide Branch, Registration Division (7505P)

This document provides the Health Effect Division’s (HED’s) risk assessment on quinclorac and 

quinclorac dimethyl amine, as proposed by BASF. The current request is for a tolerance without 

U.S. registration. HED notes that registration in Canada was proposed for the end use product, 

ACCORD SL Herbicide, active ingredient quinclorac dimethyl amine on rapeseed subgroup 

20A. However, PMRA required that the proposal be changed to the use of ACCORD DF, active 

ingredient quinclorac (acid).
Contents

1.0. Executive Summary........................................................................................................... 4

2.0. HED Recommendations.................................................................................................... 8

2.1. Data Deficiencies ............................................................................................................. 8

2.2. Tolerance Considerations................................................................................................. 8

Enforcement Analytical Method: Adequate analytical methods (GC/ECD) are available for 

enforcing quinclorac tolerances on plant (BASF Method A8902; MRID# 41063537) and 

livestock (BASF Method 268/1; MRID# 41063536) commodities. Both methods have 

undergone successful agency method validation trials and have been submitted to FDA for 

publication in PAM II as the tolerance enforcement methods. The LOQ of both methods is 

0.05 ppm for all matrices. ....................................................................................................... 8

Recommended Tolerances ...................................................................................................... 9

Revisions to Petitioned-For Tolerances and Existing Tolerances......................................... 10

International Harmonization ................................................................................................. 10

2.3. Label Recommendations................................................................................................ 10

3.0. Introduction...................................................................................................................... 10

3.1. Chemical Identity ........................................................................................................... 10

3.2. Physical/Chemical Characteristics................................................................................. 12

3.3. Pesticide Use Pattern...................................................................................................... 13

3.4. Anticipated Exposure Pathways..................................................................................... 15

3.5. Consideration of Environmental Justice ........................................................................ 15

4.0. Hazard Characterization and Dose-Response Assessment.......................................... 16

4.1. Toxicology Studies Available for Analysis .................................................................... 16

4.3. Dermal Absorption ......................................................................................................... 17

4.5. Safety Factor for Infants and Children (FQPA Safety Factor)....................................... 18

Completeness of the Toxicology Database ........................................................................... 18

4.6. Toxicity Endpoint and Point of Departure Selections.................................................... 19

Dose-Response Assessment.................................................................................................. 19

Recommendation for Combining Routes of Exposures for Risk Assessment...................... 20

Cancer Classification and Risk Assessment Recommendation ............................................ 20

Summary of Points of Departure and Toxicity Endpoints Used in Human Risk Assessment

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

5.0. Dietary Exposure and Risk Assessment......................................................................... 24

5.1. Metabolite/Degradate Residue Profile ........................................................................... 24

Summary of Plant and Animal Metabolism Studies............................................................. 24

Summary of Environmental Degradation ............................................................................. 25

Comparison of Metabolic Pathways..................................................................................... 25

Residues of Concern Summary and Rationale...................................................................... 26

5.2. Food Residue Profile...................................................................................................... 26

5.3. Water Residue Profile..................................................................................................... 27
5.4 Dietary Risk Assessment.................................................................................................... 27

6.0. Residential (Non-Occupational) Exposure/Risk Characterization ............................. 31

6.1. Residential Handler Exposure........................................................................................ 31

6.2. Residential Post-Application Exposure.......................................................................... 33

6.2.1. Residential (Non-occupational) post-application inhalation ..................................... 33

6.2.2. Residential (Non-Occupational) Post-Application Dermal and Incidental Oral ....... 33

6.3. Combined Residential Risk Estimates (Multiple Exposure Scenarios)......................... 34

6.4. Residential Risk Estimates for Use in Aggregate Assessment....................................... 34

6.5. Residential Bystander Post-application Inhalation Exposure ..................................... 35

6.6. Spray Drift...................................................................................................................... 35

7.0. Aggregate Exposure/Risk Characterization.................................................................. 36

7.1. Acute Aggregate Risk ...................................................................................................... 36

7.2. Short-Term Aggregate Risk............................................................................................ 36

7.3. Intermediate-Term Aggregate Risk ................................................................................ 37

7.4. Chronic Aggregate Risk .................................................................................................. 37

7.5. Cancer Aggregate Risk.................................................................................................... 37

7.6. Cumulative Exposure/Risk Characterization ............................................................... 38

8.0. Occupational Exposure/Risk Characterization ............................................................ 38

9.0. References......................................................................................................................... 38

Appendix A. Toxicology Profile and Executive Summaries................................................... 40

9.1. A.1 Toxicology Data Requirements............................................................................... 40

9.2. A.2 Toxicity Profiles ...................................................................................................... 41

9.3. A.3 Hazard Identification and Endpoint Selection......................................................... 45

9.4. A.4 Executive Summaries.............................................................................................. 49

Appendix B. Review of Human Research................................................................................ 58

Appendix C: International Residue Limits.............................................................................. 59
1.0. Executive Summary

Quinclorac is an herbicide for the selective post-emergent control of various annual grasses and 

broadleaf weeds. It is adsorbed via the root system and partially through the foliage and acts as 

an inhibitor of cell wall synthesis. Quinclorac is currently formulated into a variety of product 

formulations including; dry flowable, wettable powder, ready-to-use, granular, emulsifiable 

concentrate, flowable concentrate, and liquid formulations. Quinclorac is also available as the 

dimethyl amine salt. The current proposal is for a tolerance for crop group 20A without U.S. 

registration. Use of the dry flowable formulation of the end-use product ACCORD DF

Herbicide is proposed in Canada, a 75% dry flowable formulation. The maximum single 

application rates for the proposed uses are 100 g ae/A for rapeseed subgroup 20A. Accord DF 

Herbicide may be applied as a foliar spray using ground equipment only. MERGE adjuvant may

be added to the spray formulation.

A variety of end-use products containing quinclorac and quinclorac dimethyl amine are currently

registered in the U. S. on rice, sorghum, and wheat, low growing berries, except strawberries, 

subgroup 13-07H, and rhubarb. In addition to agricultural crops, quinclorac is also registered for: 

agricultural fallow/idle land/conservation reserves; nonagricultural uncultivated areas/soils; grass 

forage/fodder/hay; grasses grown for seed; pastures and rangelands; agricultural and 

nonagricultural rights of way/fencerows/hedgerows; agricultural uncultivated areas; utility

poles/rights of way; airports/landing fields; ornamental sod farms; commercial/industrial lawns. 

Additionally, quinclorac is registered for use by commercial applicators and homeowners on 

lawns, parks, in and around ornamentals, and golf courses.

A new physical form of quinclorac (EPA Reg. No. 7969-272) has recently been registered in the 

U. S.: Drive XLR-8 (Reg. No 7969-272), Paramount L Herbicide (Reg. No. 7969-315), and 

Facet L Herbicide (EPA Reg. No. 7969-316). These products are DMA (dimethylamine) salt 

forms of quinclorac. A similar product, Accord SL, was originally proposed for the use of 

quinclorac in Canada, but was not supported by adequate residue data, So, the use of ACCORD 

DF is now proposed instead.

Hazard

Quinclorac toxicity in experimental animals is observed mostly at doses above 150 mg/kg/day

following subchronic and chronic exposures. Subchronic exposure to quinclorac caused 

decreased body weight gains, increased water intake, increased liver enzymes and focal chronic 

interstitial nephritis (rats). Chronic toxic effects include body weight decrement, increase in 

kidney and liver weights, and hydropic degeneration of the kidneys (dogs). At high doses, 

chronic toxicity also includes increased incidences of pancreatic acinar cell hyperplasia and 

adenomas. Neurotoxic effects were not observed in any of the acute, subchronic and chronic 

studies with quinclorac. There was no increased qualitative or quantitative fetal or offspring 

susceptibility in the prenatal developmental studies in rats or rabbits or postnatal reproduction 

study in rats. 

There are no mutagenicity concerns. Quinclorac was classified in 1992 by the HED Cancer Peer 

Review committee (CPRC) as a group D carcinogen - not classifiable as to human 

carcinogenicity- based on recommendation by the EPA Scientific Advisory Panel. Quantification 
of risk using the chronic RfD will adequately account for all chronic effects, including 

carcinogenicity, that may result from exposure to quinclorac.

Quinclorac (technical grade material) has a low order of acute toxicity as demonstrated by

Toxicity Category III by the oral, dermal, and inhalation routes. The chemical is a mild eye 

irritant, is not a skin irritant, but was positive for dermal sensitization.

The toxicology database is complete. The HED Hazard and Science Policy Council (HASPOC) 

waived the requirement for a neurotoxicity battery (acute and subchronic neurotoxicity studies) 

and a DNT study (TXR 0056385).

Endpoints and Uncertainty Factors for Risk Assessment

Toxicity endpoints and points of departure (PODs) were selected for dietary and occupational

exposure scenarios. For the acute dietary endpoint for the sub-population females 13-49 years, a

POD of 200 mg/kg was selected from a rabbit developmental toxicity study based on increased 

rate of resorptions and post-implantation loss, a decrease in the number of live fetuses, and 

reduced fetal body weight seen at 600 mg/kg/day. A UF 100x (10x for intraspecies variation, 

10x for interspecies extrapolation and a 1x FQPA safety factor) was applied to the dose to obtain 

an acute reference dose/population adjusted dose (aRfD/aPAD) of 2.0 mg/kg. An appropriate 

endpoint attributable to a single exposure to assess dietary exposure for the general populations 

including infants and children was not available.

A chronic dietary POD of 37.5 mg/kg/day was selected for the general population from a 

carcinogenicity study in mice based on decreased body weight at 150 mg/kg/day. A UF 100x 

(10x for intraspecies variation, 10x for interspecies extrapolation and a 1x FQPA factor) was 

applied to the dose to obtain a chronic reference dose/population adjusted dose (cRfD/cPAD) of 

0.38 mg/kg/day.

A POD of 70 mg/kg/day for assessing incidental oral short-term (1-30 days) as well as shortand intermediate term inhalation exposure scenarios was selected from the developmental 

toxicity study in rabbits based on decreased maternal body weight gain and food consumption 

(and increased water consumption) at 200 mg/kg/day. This is supported by subchronic and 

chronic dietary data on mice. The LOC for MOE of 100 is applied for this exposure scenario. 

This includes 10X for interspecies extrapolation, 10X for intraspecies variation and a 1x FQPA 

SF.

A dermal endpoint was not selected because no dermal toxicity was seen at limit dose of 1000 

mg/kg/day in a 21-day dermal toxicity study. In addition, there were no susceptibility concerns.

Long-term inhalation exposure is not anticipated based on the current use pattern for quinclorac. 

Therefore, long-term PODs have not been established.

Chemistry

Permanent tolerances have been established for residues of quinclorac per se in/on barley, rice, 

sorghum, wheat, low growing berries, except strawberries, subgroup 13-07H, and rhubarb at 

levels ranging from 0.1 ppm in wheat straw to 1200 ppm in aspirated grain fractions [40 CFR 
§180.463(a)]. Permanent tolerances have also been established for residues of quinclorac, per se, 

in/on livestock commodities at levels ranging from 0.05 to 1.5 ppm. 

BASF has submitted a request for tolerances with no U. S. registration for quinclorac on 

rapeseed subgroup 20A at 1.5 ppm. Registration is proposed in Canada. 

The qualitative nature of quinclorac residues in plants was considered adequately understood for 

the currently registered crops, based upon the metabolism studies on rice, sorghum, and wheat. 

Additional metabolism data were submitted for quinclorac on canola to support use on rapeseed. 

This study showed a significant level of quinclorac methyl ester. The qualitative nature of 

quinclorac residues in livestock is also understood based upon the adequate goat and poultry

metabolism studies. In earlier risk assessments, the risk assessment team had concluded that 

parent is the only residue of concern in both plant and livestock commodities for purposes of the 

tolerance expression and risk assessment. For the current action, because of the significant level 

of quinclorac methyl ester found, the risk assessment team concluded that the residue of concern 

on canola is quinclorac and its methyl ester. 

An adequate enforcement method is available for enforcing quinclorac tolerances on plants and 

livestock (BASF Method 268/1), a gas chromatography/electron capture detection (GC/ECD)

method that uses methylation with diazomethane. There are available FDA multi-residue method 

(MRM) testing data that indicate that quinclorac is completely recovered using Protocol B. 

Updated enforcement analytical methods were submitted for determining residues of quinclorac, 

per se, in/on plant parts, an LC/MS/MS method (BASF Method D9708/1). The validated LOQ 

for quinclorac is 0.05 ppm. Quinclorac methyl ester can be determined by an LC/MS/MS 

method (BASF method D9806/02). 

In Method D9708/1, the samples are soaked in NaOH, extracted with acetone (canola oil in 

hexane), concentrated and acidified, partitioned into dichloromethane, concentrated to dryness,

and re-dissolved in NaOH solution. Canola oil extracts are partitioned with acetonitrile/

water:methanol. Both canola seed and oil extracts are cleaned up by solid phase extraction 

(SPE), and quantitated by liquid chromatography (LC) method with tandem mass spectrometry

(MS/MS) detection, monitoring 2 ion transitions.

In BASF Analytical Method D9806/02, quinclorac methyl ester residues in canola seed are 

extracted with acetone (canola oil in hexane), concentrated, then partitioned twice with 

acetonitrile:water : 5% MeOH. The sample was purified by column clean-up using a C18 solid 

phase extraction (SPE) column. Quinclorac methyl ester residues in canola seed and oil were 

quantitated by liquid chromatography (LC) method with tandem mass spectrometry (MS/MS) 

detection. The ion transitions monitored were 255 → 224 and 256 → 161. The limit of 

quantitation of the method was reported as 0.05 ppm for the metabolite quinclorac methyl ester 

in each matrix.

Adequate cattle and poultry feeding studies are available and support the current and proposed 

uses of quinclorac. Canola and flax are the only members of the rapeseed subgroup 20A which 

have processed fractions which are livestock feedstuffs. The addition of these feedstuffs does 

not change the dietary burden for livestock; therefore no revision to the current livestock 

tolerances are required to support the use on imported crop group 20A commodities
Residue field trial data are not adequate to support use of quinclorac dimethylamine salt on 

rapeseed subgroup 20A, but are adequate to support the use of quinclorac acid on this crop 

subgroup, when a single application is made at 100 g ai/ha. Therefore, PMRA has requested the 

end-use product be limited to the product containing the quinclorac acid.

Adequate processing data have been submitted to support the use of quinclorac on rapeseed 

subgroup 20A. No tolerances for processed commodities are needed.

Dietary (food+water) Exposure and Risk

Acute and chronic aggregate dietary (food and drinking water) exposure and risk assessments 

were conducted using the Dietary Exposure Evaluation Model DEEM-FCID, Version 3.16 which 

uses food consumption data from the U.S. Department of Agriculture’s National Health and 

Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA). This dietary

survey was conducted from 2003 to 2008. 

The drinking water assessment did not need to be updated for this risk assessment, because there 

is no new use proposed in the U. S. The drinking water assessment for surface water used the 

Tier I rice model. The Tier I SCI-GROW model was used to estimate groundwater 

concentrations for all uses. Surface water EDWCs for acute and chronic dietary exposure are 

both 511 μg/L. The recommended groundwater EDWC is 29 μg/L, for acute and chronic 

exposure. 

Both the acute and chronic dietary exposure assessments are highly conservative and incorporate 

tolerance/maximum residue level estimates based on field trial data for the residues of concern 

and assume 100% crop treated. Default processing factors were used and, based on empirical 

data, a processing factor of 1.5x was used for oil commodities of the Rapeseed Subgroup 20A. 

Screening-level Tier I modeling was used to estimate drinking water concentrations.

The acute (food + water) dietary risk estimate at the 95th percentile of exposure utilized 1.6% of 

the acute population adjusted dose (aPAD) for females age 13 to 49. This is the only population 

subgroup for which an acute endpoint was selected. 

The chronic (food + water) dietary risk estimates are less than or equal to 8.9% of the chronic 

population adjusted dose (cPAD) for all population subgroups. All Infants < 1 year of age is the 

most highly-exposed subgroup, utilizing 8.9% of the cPAD, while the general US population 

utilizes 3.6% of the cPAD. 

Occupational Exposure/Risk

No occupational risk assessment is needed for this risk assessment. No new use is proposed in 

the U. S. 

Residential Exposure/Risk

There are no proposed residential uses at this time; however, there are existing uses for 

quinclorac on residential, non-residential turf (i.e., athletic fields, cemeteries, parks, etc.) and sod 
farms to control several broadleaf and grass weeds that have been reassessed in this document to 

reflect updates to HED’s 2012 Residential SOPs, along with policy changes for body weight 

assumptions. Since individuals can potentially be exposed to treated turf, a residential postapplication assessment was previously conducted (T. Moriarty; 08/13/2008; D342993). Postapplication exposure and risk estimates resulted in inhalation MOEs ranging from 3600-

250,000,000. These MOEs were greater than the LOC of 100, and, therefore, were not of 

concern. 

Aggregate

In general, aggregate exposures are calculated by summing chronic dietary (food and drinking 

water) and residential exposures (residential or other non-occupational exposures). HED 

reviewed all residential sources of exposure to determine which residential exposure scenarios 

would be appropriate to combine with dietary exposure for an aggregate risk assessment. The 

only applicable exposure pathways are inhalation (for adult handlers) and incidental oral (for 

post-application exposure to children). The short-term aggregate MOEs for the adult residential 

handlers and the children were 2100 and 1600, respectively, which are above the LOC of 100 

and, therefore, not of concern. An intermediate-term adverse effect was identified; however, 

quinclorac is not registered for any use patterns that would result in intermediate-term residential 

exposure. Therefore, an intermediate-term aggregate risk assessment was not performed nor 

required. Additionally, aggregate acute and chronic (food and water) exposures were ≤100% the 

cPAD for all population subgroups as a result of all registered/proposed uses. Thus, acute and 

chronic aggregate exposure to quinclorac is not of concern. 

2.0. HED Recommendations

There are no risk concerns that would preclude establishing a tolerance for crop subgroup 20A. 

2.1. Data Deficiencies

Toxicology: None

Residue Chemistry: None for this use. 

Additional metabolism data are needed if use on dissimilar commodities is proposed.

Future field trials must include analysis for quinclorac methyl ester.

ORE: None.

2.2. Tolerance Considerations

Enforcement Analytical Method: Adequate analytical methods (GC/ECD) are available for 

enforcing quinclorac tolerances on plant (BASF Method A8902; MRID# 41063537) and 

livestock (BASF Method 268/1; MRID# 41063536) commodities. Both methods have 

undergone successful agency method validation trials and have been submitted to FDA for 

publication in PAM II as the tolerance enforcement methods. The LOQ of both methods is 0.05 

ppm for all matrices. 
In BASF Method 268/1, used for both plant and animal matrices, samples are extracted with 

acetone and dichloromethane and re dissolved in acetone/hexane. An aliquot is subjected to GC 

chromatography using a DB-5 column and electron capture detection. Methylated standard is 

used for quantitation. The LOD was reportedly 0.05 ppm, but this was also the lowest level 

validated.

Updated enforcement analytical methods were submitted for determining residues of quinclorac, 

per se, in/on plant parts, an LC/MS/MS method (BASF Method D9708/1). The validated LOQ 

for quinclorac is 0.05 ppm. Quinclorac methyl ester can be determined by an LC/MS/MS 

method (BASF method D9806/02). 

In Method D9708/1, for the determination of quinclorac, per se, the samples are soaked in 

NaOH, extracted with acetone (canola oil in hexane), concentrated and acidified, partitioned into 

dichloromethane, concentrated to dryness, and re dissolved in NaOH solution. Canola oil 

extracts are partitioned with acetonitrile/ water:methanol. Both canola seed and oil extracts are 

cleaned up by solid phase extraction (SPE), and quantitated by liquid chromatography (LC) 

method with tandem mass spectrometry (MS/MS) detection, monitoring 2 ion transitions.

In Method D9806/02, for the determination of quinclorac methyl ester, residues in canola seed 

were extracted with acetone, mixed with hexane (canola oil extracted with hexane), then 

partitioned with 95% 2:1 acetonitrile:water (v/v), 5% MeOH. The sample was cleaned-up using a 

C18 solid phase extraction (SPE) column. Quinclorac methyl ester residues in canola seed and 

oil were quantitated by liquid chromatography (LC) with tandem mass spectrometry (MS/MS) 

detection, monitoring 2 ion transitions.

Quinclorac is detected by FDA Multiresidue Protocol B, but not the other FDA Multiresidue 

Method (MRM) Protocols.

Recommended Tolerances

The current tolerance expression for quinclorac is: 

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

degradates, in or on the commodities in the table in this paragraph. Compliance with the 

tolerance levels specified in this paragraph is to be determined by measuring only quinclorac, 

3,7-dichloro-8-quinolinecarboxylic acid, in or on the commodity.”

The current tolerance expression is in accord with our current guidance on tolerance expressions. 

(S. Knizner, 5/10/2009) However, in addition to parent quinclorac, quinclorac methyl is also a 

residue of concern in rapeseed, subgroup 20A. The tolerance expression for rapeseed should be 

as follows, in a separate subsection of 40 CFR §180.463. The rapeseed subgroup 20A tolerance 

should have a footnote indicating that there is no U. S. registration.

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

degradates, in or on the commodities in the table in this paragraph. Compliance with the 

tolerance levels specified in this paragraph is to be determined by measuring only quinclorac, 

3,7-dichloro-8-quinolinecarboxylic acid, and its methyl ester, methyl-3,7-dichloro-8-
quinolinecarboxylate, calculated as the stoichiometric equivalent of quinclorac, in or on the 

commodity.”

Current Petition: Tolerance recommendations for the current petition (2E8035) for residues of 

quinclorac on rapeseed subgroup 20A are in Table 2.2.2. 10. The tolerance should go into a 

separate subsection of 180.463, because the residue definition is different. Additionally, a 

footnote is needed indicating that there are no U. S. registrations.

Table 2.2.2 Tolerance Summary for Quinclorac. § 180.463

Commodity Current/Proposed 

Tolerance (ppm)

Recommended 

Tolerance (ppm)

Comments; Correct Commodity 

Definition

Rapeseed subgroup 20A 1.0 1.5 Revised level based on OECD tolerance 

calculation procedures.

Revisions to Petitioned-For Tolerances and Existing Tolerances

Current Petition: Revisions are recommended to petitioned-for tolerances due to the use of the 

OECD tolerance calculation procedures. The recommended changes are documented in Table 

2.2.2.

Registration Review Recommendations: HED continues to recommend for the revocation of the 

tolerance on grain, aspirated fractions as it is not needed, and for the resulting lowering of 

tolerances in livestock commodities, as documented in D397719, 404569, 404912 (S. Hummel, 

9/12/2012).

International Harmonization

CODEX has not established any established maximum residue limits (MRLs) for quinclorac. 

Canada has established maximum residue limits (MRLs) for quinclorac on selected agricultural 

commodities but not the commodities in the current petition. The current petition is a workshare 

with PMRA, and MRLs for quinclorac on rapeseed subgroup 20A will be established 

concurrently. Therefore there are no issues with respect to international harmonization 

associated with this tolerance petition.

2.3.Label Recommendations

This action is limited to a request for a tolerance without U.S. registration; therefore a discussion 

of label recommendations is not pertinent.

3.0. Introduction

3.1. Chemical Identity
Quinclorac is a herbicide for the selective post-emergent control of various annual grasses and 

broadleaf weeds. Quinclorac is adsorbed via the root system and partially through the foliage 

and acts as an inhibitor of cell wall synthesis. The nomenclature of quinclorac and quinclorac 

DMA salt are summarized in Table 3.1. 
Table 3.1. Quinclorac and Quinclorac (DMA salt) Nomenclature.

Compound

N

Cl

Cl

O

OH

Common name Quinclorac,

Company experimental name BAS 514 34H 

IUPAC name 3,7-dichloroquinoline-8-carboxylic acid

CAS name 3,7-dichloro-8-quinolinecarboxylic acid

CAS registry number 84087-01-4

Molecular weight 242.1

End-use product (EP) Drive® 75 DF 

Compound

Common name Quinclorac, DMA salt

Company experimental name BAS 514 51H 

IUPAC name 3,7-dichloroquinoline-8-carboxylic acid, DMA salt

CAS name 3,7-dichloro-8-quinolinecarboxylic acid, DMA salt

CAS registry number 84087-48-9

Molecular weight 287.2

End-use product (EP) Drive®XLR8 Herbicide, EPA Reg. No. 7969-272; Paramount® L Herbicide, EPA 

Reg. No. 7969-GRA; Facet L Herbicide, EPA Reg. No. 7969-GRL

3.2. Physical/Chemical Characteristics

The physicochemical properties of the technical grade quinclorac are summarized in Table 3.2.1. 

Only a few physicochemical properties of the DMA salt of quinclorac are available (Table 3.2.2). 

The physical and chemical properties of quinclorac indicate that it is unlikely to volatilize and 

has low potential to accumulate in fatty tissues. 

N

Cl

Cl

O O

HN

CH3

CH3

H

+
Table 3.2.1 Physicochemical Properties of the Technical Grade Quinclorac.

Parameter Value Reference

Melting point/range ~269°C D342446, M. Doherty, 

9/11/07

pH 3.4-3.5 RCB 3283 S. Hummel, 

2/26/88

Density ~560 g/L D342446, M. Doherty, 

Wa 9/11/07 ter solubility (20°C) 0.0064 g/100 mL

Solvent solubility (g/100 mL at 20°C to 

25°C)

ethanol 0.2 toluene <0.1

Lutrol® <0.1 acetone 0.2

olive oil <0.1 n-octanol <0.1

acetonitrile <0.1 1,2-propandiol <0.1

ethyl acetate 0.1 dichloromethane <0.1

ethyl ether 0.1 n-hexane <0.1

Vapor pressure (20°C) <1.0×10-7 mbar (<0.75×10-7 Torr)

Dissociation constant, pKa 4.34 at 20°C

4.35 at 25°C

Octanol/water partition coefficient, log 

POW (20°C)

1.76 at pH 4

-0.74 at pH 7

3.74 at pH 10

UV/visible absorption spectrum 314 nm, 300 nm, 278 nm (95% ethanol) MRID 48051092

Table 3.2.2 Physicochemical Properties of the Quinclorac, DMA Salt.

Parameter Value Reference

Melting point/range NA

pH NA

Density NA

Water solubility (20°C) NA

Solvent solubility (g/100 mL at 20°C to 

25°C)

NA

Vapor pressure (20°C) NA

Dissociation constant, pKa 4.33 ± 0.15 (Temperature not reported) MRID 48051092

Octanol/water partition coefficient, log 

POW (20°C)

NA

UV/visible absorption spectrum 314 nm, 300 nm, 278 nm (95% ethanol) MRID 48051092

3.3. Pesticide Use Pattern

Proposed new uses. BASF is proposing use of Accord SL (Registered in Canada to BASF, Reg. 

No. 25118), containing the dimethylamine salt of quinclorac, 180 g quinclorac ae/L, in 

connection with the current petition. PMRA has requested that use of Accord SL be withdrawn 

and use of Accord DF, containing 75% quinclorac be used instead. A summary of the proposed 

Canadian use patterns for the two formulations is shown below.
Table 3.3.1. Summary of Canadian Directions for Proposed Use of Quinclorac on Rapeseed Subgroup 20A

Formulation 

Applic. 

Timing, Type, 

and Equip.

Max. Single 

Application 

Rate 

(lb ai/A)

Max. No. 

Applic. per 

Season

Max. Seasonal 

Application 

Rate (lb ai/A)

PHI 

(days)

Use Directions and 

Limitations

Canola*, Clearfield canola quality Brassica juncea, and tame mustard (brown and oriental)

ACCORD SL 180 g/L

ae quinclorac

Foliar ground 

boom 

application 

100 NS 100 60

Apply in 100 L water, when 

weeds are small and not actively 

growing. Use MERGE adjuvant 

at 0.5-1.0 L/100 L Do not apply 

by air.

ACCORD DF 75% 

quinclorac

Foliar ground 

boom 

application

100 NS 100 60

Apply in 100 L water, when 

weeds are small and not actively 

growing. Use MERGE adjuvant 

at 0.5-1.0 L/100 L Do not apply 

by air.

 Canola includes Brassica napus – all varieties, including conventional, Clearfield, LibertyLink 

and Roundup Ready
Page 15 of 59

3.4. Anticipated Exposure Pathways

The Registration Division has requested an assessment of human health risk to support the 

proposed new uses of quinclorac. The variety of end-use products containing quinclorac 

currently registered in the U. S. as follows; rice, sorghum, wheat, rhubarb, and low growing 

berries (except strawberry). In addition to agricultural crops, quinclorac is also registered for: 

agricultural fallow/idle land/conservation reserves; nonagricultural uncultivated areas/soils; grass 

forage/fodder/hay; grasses grown for seed; pastures and rangelands; agricultural and 

nonagricultural rights of way/fencerows/hedgerows; agricultural uncultivated areas; utility

poles/rights of way; airports/landing fields; ornamental sod farms; commercial/industrial lawns. 

Additionally, quinclorac is registered for use by commercial applicators and homeowners on 

lawns, parks, in and around ornamentals, and golf courses. The new uses include the following 

crops: rapeseed subgroup 20A to be imported into the US (dietary exposure pathway only). 

Humans may be exposed to quinclorac in food and drinking water, since quinclorac may be 

applied directly to growing crops and application may result in quinclorac reaching surface and 

ground water sources of drinking water. In the occupational and residential settings, inhalation 

exposure is expected to be of short- and intermediate term durations based on the activity use 

pattern. Long-term exposures (greater than 6 months) are not anticipated based on the proposed 

use pattern. No dermal endpoint was selected, therefore, only inhalation exposure was quantified. 

Incidental oral residential exposures (short-term only) are also expected.

Risk assessments have been previously prepared for the existing uses of quinclorac. This risk 

assessment considers all of the aforementioned exposure pathways based on the proposed new 

uses of quinclorac, but also considers the existing uses as well, particularly for the dietary

exposure assessment. 

3.5. Consideration of Environmental Justice

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

human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions 

to Address Environmental Justice in Minority Populations and Low-Income Populations," 

(http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf. As a part of every pesticide risk 

assessment, OPP considers a large variety of consumer subgroups according to well-established 

procedures. In line with OPP policy, HED estimates risks to population subgroups from 

pesticide exposures that are based on patterns of that subgroup’s food and water consumption, 

and activities in and around the home that involve pesticide use in a residential setting. 

Extensive data on food consumption patterns are compiled by the USDA under the Continuing 

Survey of Food Intake by Individuals (CSFII) and are used in pesticide risk assessments for all 

registered food uses of a pesticide. These data are analyzed and categorized by subgroups based 

on age, season of the year, ethnic group, and region of the country. Additionally, OPP is able to 

assess dietary exposure to smaller, specialized subgroups and exposure assessments are 

performed when conditions or circumstances warrant. Whenever appropriate, non-dietary

exposures based on home use of pesticide products and associated risks for adult applicators and 

for toddlers, youths, and adults entering or playing on treated areas post-application are 

evaluated. Further considerations are currently in development as OPP has committed resources 
Page 16 of 59

and expertise to the development of specialized software and models that consider exposure to 

bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific 

subgroups.

4.0. Hazard Characterization and Dose-Response Assessment

HED reviewed the toxicity database for quinclorac as well as the most recent risk assessment 

which was conducted in association with the new use on rhubarb and low growing berries 

(except strawberry) (D404794, J. Kidwell. et al, 11/6/2012) and concluded that no changes in 

the points of departure (PODs) or FQPA SF (1x) are warranted. Since the last risk assessment the 

immunotoxicity study in mice was submitted and reviewed (TXR 0052889). The results of this 

study did not impact the overall risk assessment. 

4.1. Toxicology Studies Available for Analysis

The toxicology database for quinclorac is adequate for evaluating and characterizing its toxicity

and selecting endpoints for purposes of risk assessment. Studies considered for this assessment 

include acute lethality (oral, dermal and inhalation routes), primary eye and dermal irritation, 

dermal sensitization, subchronic oral toxicity (rat and mouse), rat 21-day dermal toxicity, dog 

chronic toxicity, rat combined chronic toxicity/carcinogenicity, mouse carcinogenicity, 

developmental toxicity (rat and rabbit), rat two-generation reproductive toxicity, genotoxicity, rat 

metabolism, and mouse immunotoxicity. Since the last risk assessment, the HED HASPOC 

waived the requirement for a neurotoxicity battery (acute and subchronic) and a DNT study

based on a weight of the evidence (WOE) approach that considered (1) lack of neurotoxic effects 

in the available acute, subchronic, chronic, developmental, and reproduction studies; (2) the 

selected endpoints are considered to be protective of neurotoxic effects; (3) dietary exposure to 

quinclorac is low; and (4) residential and occupational MOEs are high (HASPOC TXR 

0056385). The requirement of a 28-day inhalation toxicity study was also waived previously 

based on low volatility, low acute inhalation toxicity and large extrapolated inhalation MOE 

(D376603, 23 September 2010). 

4.2. Absorption, Distribution, Metabolism, & Elimination (ADME)

The metabolism of quinclorac ((2,3,4-

14C)3,7-dichloro-8- quinolinecarboxylic acid) following 

oral administration was studied extensively in male and female CD rats. The compound was 

rapidly absorbed and eliminated in the urine following administration of single oral doses of 

(

14C) quinclorac at 15 or 600 mg/kg or after daily exposures of unlabeled compound at 15 mg/kg 

for 14 days followed by a single 15 mg/kg oral dose of labeled compound. Elimination in the 

urine 5 days after dosing accounted for 91 to 98 % of the dose with only 1 to 4 % eliminated in 

the feces. No radioactivity was detected in expired air. Biliary excretion was significant (11.5 to 

14.5 % of the dose) in animals receiving 600 mg/kg. However, most of this radioactivity was 

reabsorbed from the intestines and eliminated in the urine. Most of the radioactivity in the bile is 

associated with the glucuronide conjugate of quinclorac. The conjugate is apparently hydrolyzed 

in the intestines and reabsorbed. Almost all the radioactivity in the urine is unchanged 

quinclorac. Radioactive tissue residue levels 5 days after dosing were dose-dependent. Results 

from these and whole-body autoradiography and time-course studies indicate that relatively 
Page 17 of 59

higher radioactivity levels were detected in the adrenal glands, bone marrow, thyroid, squamous 

epithelium of the non-fundic stomach, and ovaries compared to the other body organs/tissues. In 

7-day time-course studies (oral gavage at 15 mg/kg/day or dietary at about 1,000 mg/kg/day) 

maximum 14C residue levels were detected 30 minutes after the final dose; thereafter, residue 

levels decreased with time. Mean 14C residues in plasma were also detected at 30 minutes in 

animals receiving single oral doses of 15, 100, or 600 mg/kg or 15 mg/kg/day for 7 days. 

Elimination was biphasic with half-lives of 3 to 4 hours for the rapid phase at the low doses and 

a half-life of about 13 hours at 600 mg/kg. Peak plasma levels of radioactivity in animals 

receiving higher doses (1200 mg/kg or 600 mg/kg/day for 7 days) were noted for 7 to 48 hours 

post dosing; saturation kinetics were also noted at these higher doses.

4.3. Dermal Absorption

Dermal penetration studies on quinclorac are not available. There was no dermal toxicity seen at 

the limit dose of 1000 mg/kg/day in a 21-day dermal toxicity study in rabbits.

4.4.Toxicological Effects

Quinclorac toxicity in experimental animals is observed mostly at doses above 150 mg/kg/day

following subchronic and chronic exposures. Subchronic toxicity includes decreased body

weight gains, increased water intake, increased liver enzymes (SGOT, SGPT) and focal chronic 

interstitial nephritis (rats). Chronic toxic effects include body weight decrement, increase in 

kidney and liver weights, and hydropic degeneration of the kidneys (dogs). At high doses, 

chronic toxicity also includes increased incidences of pancreatic acinar cell hyperplasia and 

adenomas (rats). Neurotoxic effects were not observed in any of the acute, subchronic and 

chronic studies with quinclorac. 

There was no increased qualitative or quantitative fetal or offspring susceptibility in the prenatal 

developmental or postnatal reproduction studies. Developmental toxicity in the rabbit consisted 

of increased resorptions, post-implantation loss, decreased number of live fetuses, and reduced 

fetal body weight. These effects occurred at much higher doses than the maternal effects of 

decreased food consumption and increased water consumption and decreased body weight gain. 

In the rat no developmental toxicity was observed at the highest dose tested (438 mg/kg/day). In 

the 2-generation reproduction study, parental toxicity and offspring toxicity occurred at the same 

dose. Parental toxicity consisted of reduced body weight in both sexes during premating and 

lactation periods. Offspring toxicity consisted of decreased pup weight, developmental delays 

and possible marginal effect on pup viability. No reproductive toxicity occurred at the highest 

dose tested (480 mg/kg/day). 

There are no mutagenicity concerns. Quinclorac is not mutagenic in bacterial assays and does 

not cause unscheduled DNA damage in primary rat hepatocytes. There is also no evidence of a 

genotoxic response in whole animal test systems (in vivo mouse bone marrow micronucleus 

assay). Quinclorac was negative in a mammalian cell in vitro cytogenetic chromosomal 

aberration assay in Chinese hamster ovary cells (CHO). 
Page 18 of 59

Quinclorac was classified in 1992 by the HED Cancer Peer Review committee (CPRC) as a 

group D carcinogen - not classifiable as to human carcinogenicity- based on recommendation by 

the EPA Scientific Advisory Panel (TXR# 0010416). This classification was based on equivocal 

increase in the incidence of one type of benign tumor (pancreatic acinar cell adenomas) in only

one sex and one species of animals (male Wistar rats). Based on this classification, a

quantification of cancer risk is not warranted because the chronic RfD will adequately account 

for all chronic effects, including carcinogenicity, likely to result from exposure to quinclorac.

Quinclorac (technical grade material) has a low order of acute toxicity as demonstrated by

Toxicity Category III by the oral, dermal, and inhalation routes. The chemical is a mild eye 

irritant, is not a skin irritant, but was positive for dermal sensitization.

The complete toxicity profile for quinclorac is provided in Appendix A. 

4.5. Safety Factor for Infants and Children (FQPA Safety Factor)

The FQPA Safety Factor Committee recommended in 1998 that the 10x factor for the protection 

of infants and children (as required by FQPA) be removed (TXR 0012902). The removal of the 

10x factor is based on 1) completeness of the data base; 2) there is no indication of increased 

susceptibility of rats or rabbit fetuses to in utero and/or postnatal exposure in the developmental 

and reproductive toxicity data; 3) unrefined (Tier 1) dietary exposure estimates are protective 

since they exaggerate the dietary exposure estimates; and 4) modeling data are used for ground 

and surface source drinking water exposure assessments resulting in conservative upper-bound 

concentrations.

Completeness of the Toxicology Database

The toxicology database for quinclorac is complete and the risk assessment team has concluded 

that the FQPA safety factor can be reduced to 1x. The following acceptable studies are available 

for FQPA consideration: (1) Developmental toxicity studies in rats and rabbits; and (2) Twogeneration reproduction study in rats. Acute and subchronic neurotoxicity studies have been 

waived per HASPOC (TXR# 0056385).

 

4.5.1. Evidence of Neurotoxicity

There are no acute, subchronic or chronic neurotoxicity studies on quinclorac available from the 

registrant or from the published literature. Neurotoxic effects were not observed in any of the 

acute, subchronic and chronic studies with quinclorac. Because of the lack of evidence of 

neurotoxic effects, HIARC (TXR# 0012717) determined in 1998 that no acute, subchronic, or 

developmental neurotoxicity studies are required for quinclorac. This was confirmed by 

HASPOC in 2012 (TXR# 0056385). 

4.5.2. Evidence of Sensitivity/Susceptibility in the Developing or Young 

Animal
Page 19 of 59

The toxicology database for quinclorac is adequate for the FQPA assessment. Developmental 

toxicity studies in rats and rabbits and the reproduction studies in rats provided no indication of 

increased qualitative or quantitative susceptibility.

4.5.3. Residual Uncertainty in the Exposure Database

There are no residual uncertainties with regard to dietary and residential/occupational exposure. 

The dietary exposure assessments are based on tolerance level residues and 100% crop treated 

information. Modeled values were used for drinking water estimates. Occupational and 

residential exposure assessments are based on reasonable worst-case assumptions and will not 

likely underestimate potential exposure or risk. Based on these data, the quinclorac risk 

assessment team concluded that no additional safety factor is needed to account for exposure 

considerations.

4.6. Toxicity Endpoint and Point of Departure Selections

Dose-Response Assessment

Toxicity endpoints and points of departure (PODs) for dietary and occupational exposure 

scenarios are summarized below. A detailed description of the studies used as a basis for the 

selected endpoints are presented in Appendix A. 

An appropriate endpoint attributable to a single exposure to assess dietary exposure for the 

general populations including infants and children was not available from the oral toxicity

studies including the rat and rabbit developmental toxicity studies.

An acute dietary POD of 200 mg/kg (NOAEL) for the sub-population females 13-49 years old 

was selected from a rabbit developmental toxicity study based on increased rate of resorptions 

and post-implantation loss, a decrease in the number of live fetuses, and reduced fetal body

weight seen at 600 mg/kg/day. A UF 100x (10x for intraspecies variation, 10x for interspecies 

extrapolation and a 1x FQPA safety factor) was applied to the dose to obtain an acute reference 

dose/population adjusted dose (aRfD/aPAD) of 2.0 mg/kg.

A chronic dietary POD of 37.5 mg/kg/day (NOAEL) was selected for the general population 

from a carcinogenicity study in mice based on effects on decreased body weight at 150 

mg/kg/day. A UF 100x (10x for intraspecies variation, 10x for interspecies extrapolation and a 

1x FQPA factor) was applied to the dose to obtain a chronic reference dose/population adjusted 

dose (cRfD/cPAD) of 0.38 mg/kg/day.

A POD of 70 mg/kg/day (NOAEL) for assessing incidental oral short-term (1-30 days) as well as 

short- and intermediate term inhalation exposure scenarios was selected from the developmental 

toxicity study in rabbits based on decreased maternal body weight gain and food consumption 

(and increased water consumption) at 200 mg/kg/day. This is supported by subchronic and 

chronic dietary data on mice. The LOC for MOE of 100 is applied for this exposure scenario. 

This includes 10X for interspecies extrapolation, 10X for intraspecies variation and a 1x FQPA 

SF.
Page 20 of 59

A dermal endpoint was not selected because an appropriate endpoint was not available (i.e. no 

dermal toxicity was seen at limit dose of 1000 mg/kg/day in a 21-day dermal toxicity study). In 

addition, there were no susceptibility concerns.

Long-term inhalation exposure is not anticipated based on the current use pattern for quinclorac. 

Therefore, long-term PODs have not been established.

Recommendation for Combining Routes of Exposures for Risk Assessment

Under FQPA, when there are potential residential exposures to the pesticide, aggregate risk 

assessment must consider exposures from three major sources: oral, dermal and inhalation 

exposures. These combined residential exposures must then be aggregated with dietary exposure 

(food and drinking water) to determine aggregate risk. Dermal exposures were not quantified due 

to a lack of a dermal toxicological endpoint. Because the inhalation and incidental oral endpoints 

are based on the same endpoint from the same study, the developmental rabbit, exposures from 

these routes may be combined.

Cancer Classification and Risk Assessment Recommendation

Quinclorac was classified in 1992 by the HED Cancer Peer Review committee (CPRC) as a 

group D carcinogen - not classifiable as to human carcinogenicity- based on recommendation by

the EPA Scientific Advisory Panel (TXR# 0010416). This classification was based on equivocal 

increase in the incidence of one type of benign tumor (pancreatic acinar cell adenomas) in only

one sex and one species of animals (male Wistar rats). Quantification of risk using the chronic 

RfD will adequately account for all chronic effects, including carcinogenicity, that may result 

from exposure to quinclorac. There was no evidence of carcinogenicity in mice or female rats.

Summary of Points of Departure and Toxicity Endpoints Used in Human Risk Assessment

Toxicological doses and endpoints for dietary and non-occupational human health risk 

assessments for quinclorac are presented below in Table 4.5.4.1.
Page 21 of 59

Table 4.5.4.1. Summary of Toxicological Doses and Endpoints for Quinclorac for Use in Dietary and NonOccupational Human Health Risk Assessments.

Exposure/

Scenario

Point of 

Departure

Uncertainty/FQPA 

Safety Factors

RfD, PAD, 

Level of 

Concern 

for Risk 

Assessment

Study and Toxicological Effects

Acute Dietary 

(General 

Population, 

including 

Infants and 

Children)

Not applicable. An endpoint for acute dietary exposure to the general population was not selected 

because there was no available endpoint attributable to a single dose that was appropriate for this 

scenario (effects observed in the available studies are presumed to require more than one 

exposure).

Acute Dietary

(Females 13-

49 years of 

age)

NOAEL

(developmental

) = 200 

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF= 1x

aRfD = 2.0 

mg/kg/day

aPAD = 2.0 

mg/kg/day

Developmental toxicity study in rabbits 

(MRID# 41063525 and 41680501) 

Developmental toxicity LOAEL = 600 

mg/kg/day based on increased early 

resorptions and postimplantation loss, 

decreased live fetuses, decreased fetal 

body weight. These fetal effects are 

presumed to occur after a single dose.

Chronic 

Dietary (All 

Populations)

NOAEL= 37.5 

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF= 1x

cRfD = 0.38

mg/kg/day

cPAD = 

0.38 

mg/kg/day

Carcinogenicity study in mice 

(MRID # 41063523)

LOAEL = 150 mg/kg/day based on 

decreased body weight.

Incidental 

Oral ShortTerm (1-30 

days) 

NOAEL= 70 

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF= 1x

Residential 

LOC for 

MOE = 100

Developmental toxicity study in rabbits. 

(MRID# 41063525 and 41680501)

Maternal toxicity LOAEL = 200 

mg/kg/day based on decreased maternal 

body weight gain and food consumption, 

and increased water consumption.

Dermal (all 

durations)

Not applicable. A dermal endpoint was not selected because an appropriate endpoint was not 

available (no dermal toxicity was seen at the limit dose of 1000 mg/kg/day in a 21-day dermal 

toxicity study).

Inhalation 

Short-Term

(1-30 days) 

and 

IntermediateTerm (1-6 

months)

NOAEL= 70 

mg/kg/day

[Inhalation 

absorption rate 

= 100% relative 

to oral 

absorption]

UFA= 10x 

UFH= 10x

FQPA SF= 1x

Residential 

LOC for 

MOE = 100

Developmental toxicity study in rabbits. 

(MRID# 41063525 and 41680501)

Maternal toxicity LOAEL = 200 

mg/kg/day based on decreased maternal 

body weight gain and food consumption, 

and increased water consumption.

Inhalation 

Long-Term 

(>6 months)

Not applicable. Long-term inhalation exposure is not anticipated under current use scenarios.

Cancer (oral, 

dermal, 

inhalation)

Quinclorac was classified in 1992 by the HED Cancer Peer Review committee (CPRC) as a group 

D carcinogen - not classifiable as to human carcinogenicity- based on recommendation by the EPA 

Scientific Advisory Panel (TXR# 0010416). This classification was based on equivocal increase in 

the incidence of one type of benign tumor (pancreatic acinar cell adenomas) in only one sex and 

one species of animals (male Wistar rats). Quantification of risk using the chronic RfD will 

adequately account for all chronic effects, including carcinogenicity, that may result from exposure 

to quinclorac. There was no evidence of carcinogenicity in mice or female rats. 
Page 22 of 59

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and 

used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human 

exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = 

uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in 

sensitivity among members of the human population (intraspecies). UFL = use of a LOAEL to extrapolate a 

NOAEL. UFS = use of a short-term study for long-term risk assessment. UFDB = to account for the absence of key 

date (i.e., lack of a critical study). FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = 

chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. N/A = not applicable.
Page 23 of 59

Table 4.5.4.2 Summary of Toxicological Doses and Endpoints for Quinclorac for Use in Occupational Human 

Health Risk Assessments

Exposure/ 

Scenario

Point of 

Departure

Uncertainty 

Factors

Level of Concern 

for Risk 

Assessment

Study and Toxicological Effects

Dermal (all 

durations)

Not applicable. A dermal endpoint was not selected because an appropriate endpoint was not 

available (no dermal toxicity was seen at the limit dose of 1000 mg/kg/day in a 21-day dermal 

toxicity study).

Inhalation 

Short-Term (1-

30 days) and 

IntermediateTerm (1-6 

months)

NOAEL=70 

mg/kg/day

[Inhalation 

absorption 

rate = 100% 

relative to 

oral 

absorption]

UFA= 10x 

UFH= 10x

FQPA SF= 1x

Occupational

LOC for MOE = 

100

Developmental toxicity study in rabbits. 

(MRID# 41063525 and 41680501)

Maternal toxicity LOAEL = 200 

mg/kg/day based on decreased maternal 

body weight gain and food consumption, 

and increased water consumption.

Cancer (oral, 

dermal, 

inhalation)

Quinclorac was classified in 1992 by the HED Cancer Peer Review committee (CPRC) as a group 

D carcinogen - not classifiable as to human carcinogenicity- based on recommendation by the 

EPA Scientific Advisory Panel (TXR# 0010416). This classification was based on equivocal 

increase in the incidence of one type of benign tumor (pancreatic acinar cell adenomas) in only 

one sex and one species of animals (male Wistar rats). Quantification of risk using the chronic 

RfD will adequately account for all chronic effects, including carcinogenicity, that may result 

from exposure to quinclorac.. There was no evidence of carcinogenicity in mice or female rats.

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and 

used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human 

exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = 

uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in 

sensitivity among members of the human population (intraspecies). UFL = use of a LOAEL to extrapolate a 

NOAEL. UFS = use of a short-term study for long-term risk assessment. UFDB = to account for the absence of key 

data (i.e., lack of a critical study). MOE = margin of exposure. LOC = level of concern. N/A = not applicable.
Page 24 of 59

5.0. Dietary Exposure and Risk Assessment 

5.1. Metabolite/Degradate Residue Profile

Summary of Plant and Animal Metabolism Studies

The qualitative nature of quinclorac residues in plants was considered adequately understood for 

the currently registered uses, based upon the metabolism studies on rice, grain sorghum, and 

wheat. In each of these studies, the major 14C-residue in/on various matrices was identified as 

parent compound. Based on the metabolite profiles observed in these studies, quinclorac 

undergoes hydroxylation of the quinoline ring of the parent, followed by conjugation with 

glucose and other biologically available compounds at the hydroxylated site. Some radioactive 

residues are incorporated into the high molecular weight natural products. Based on the above 

studies, The HED risk assessment team concluded that parent is the only residue of concern in 

plant commodities for purposes of the tolerance expression and risk assessment, although the 

methyl ester of quinclorac was present as a minor metabolite. All three metabolism studies are 

on grain commodities. A 4

th metabolism study, on canola, was reviewed in connection with this 

petition. Based on the quinclorac metabolism in canola, the joint EPA/PMRA risk assessment 

team concluded that the quinclorac methyl ester should be included in the residue of concern for 

both risk assessment and enforcement.

Metabolism in Canola: The majority (84%) of the TRRs in canola seed was extractable and a 

total of 91% was either identified (74.1%) or characterized (17.4%). Identification of the TRRs 

resulted in the identification of parent (37.1% of TRRs) and quinclorac methyl ester (37.1% of 

TRRs). The results indicated that a significant portion of the residue was present in the 

harvested seed. As quinclorac was applied prior to seed pod formation, the presence of TRRs in 

the mature seed is an indication of the translocation of the TRRs. 

The methyl ester of quinclorac was reported in some grain commodities at <15% of the TRR. 

The methyl ester is expected to be measured by the enforcement method, which includes a 

methylation step to measure all residues as quinclorac methyl ester. Quinclorac methyl ester 

was also observed as a minor metabolite (< 10% of the residue) in rotational crops. This 

metabolite was not observed in livestock studies and was not seen in the rat metabolism study (a 

gluco conjugate through the carboxylic acid functional group was postulated to be present in rat 

urine at ≈1% of the dose).

Additional metabolism data will be needed if use on dissimilar commodities is proposed.

860.1300 Nature of the Residue - Livestock

D241204, J. Stokes, 11/6/1998

D325790, M. Doherty, 9/13/2007

The qualitative nature of quinclorac residues in livestock is understood based upon the adequate 

goat and poultry metabolism studies (MRIDs 41076104 and 41063535, respectively). In both 

studies, quinclorac was the principal residue identified in each commodity. HED concluded that 

parent is the only residue of concern for risk assessment and tolerance expression for livestock. 
Page 25 of 59

However, the enforcement method includes a methylation step and determines the methyl ester 

of quinclorac. 

In a rat metabolism study (MRID 41063533), quinclorac was the primary metabolite reported. 

Elimination was primarily in the urine (91-98%) with small amounts in the feces (1-4%) 

eliminated by day 5 after dosing.

Conclusions. No further livestock metabolism data are required at the present time.

Summary of Environmental Degradation

M. Lowit, N. Andrews, D397720, 8/9/12; M. Lowit, N. Andrews, D405093, 9/14/12

Vapor pressure (7.5 x 10-8 mm Hg at 20o C) and Henry's Law Constant (1.22 to 24.3 x 10-15

atm.m3 mol-1) indicate a low possibility of volatilization from soil and water. Laboratory data 

indicate that quinclorac is stable to hydrolysis, photolysis in sterile water, aerobic soil 

metabolism, and aquatic metabolism (aerobic and anaerobic). Conversely, quinclorac undergoes 

rapid photolysis in non-sterile rice paddy, natural river waters, and solutions containing activated 

sewage sludge (half-lives of 5-10 days). Photolysis on soil surface is also a route of dissipation 

with a mean half life of 141 days. Based on available laboratory studies, two major (BH 514-1 

and BH 514 2-OH; >10% applied) and one minor (BH 514-HMe-ester; <10% applied) 

metabolites of quinclorac were identified. The adsorption coefficients for quinclorac and its 

degradation products suggest that leaching could be a route of dissipation. Field studies indicate 

that quinclorac is moderately persistent to persistent (18-176 day half-lives) in terrestrial 

environments. The octanol/water partition coefficient (KOW) of 0.266 also suggests that 

quinclorac has a low potential to bioaccumulate. A detailed assessment of the environmental fate 

of quinclorac can be found in the new chemical risk assessment (DP 250179).

Comparison of Metabolic Pathways

Quinclorac was the predominant metabolite in all 3 plant metabolism studies (all in grains), the 

new quinclorac metabolism study in canola, and in the livestock metabolism study and the rat 

metabolism study. Small amounts of the quinclorac methyl ester in plants were reported. 

Quinclorac methyl ester is a major metabolite in canola (present at >10%).

The primary path by which plants metabolize quinclorac is through the hydroxylation of the 

quinoline ring of the parent, followed by the conjugation of glucose and other biologically

available compounds at the hydroxylated site. Ultimately, some radioactive residues are 

incorporated into the high molecular weight natural products. The forage, fodder, and straw 

reported a number of aqueous metabolites, which would be polar metabolites, such as 

hydroxylated metabolites or conjugates.

The qualitative nature of quinclorac residues in livestock is understood based upon adequate goat 

and poultry metabolism studies (MRIDs 41076104 and 41063535, respectively). Quinclorac was 

the principal residue identified in each commodity. Quinclorac methyl ester was not reported as 

a livestock metabolite.
Page 26 of 59

In a rat metabolism study (MRID 41063533), quinclorac was the primary metabolite reported. 

Elimination was primarily in the urine (91-98%) with small amounts in the feces (1-4%) 

eliminated by day 5 after dosing. Quinclorac methyl ester was not reported as a rat metabolite.

Residues of Concern Summary and Rationale

Quinclorac was not reviewed by ROCKs or its predecessors. Previous risk assessment teams 

determined that quinclorac was the residue of concern since it was the predominant residue, and 

there were no other primary metabolites. In the case of canola, quinclorac methyl ester was a 

primary metabolite, comprising a significant portion of the residue. The current joint EPA/PMRA

risk assessment team determined that the residue of concern in canola was quinclorac plus its 

methyl ester for both risk assessment and enforcement.

Table 5.1.4 Summary of Metabolites and Degradates to be included in the Risk 

Assessment and Tolerance Expression

Matrix Residues included in Risk 

Assessment

Residues included in 

Tolerance Expression

Plants

Rapeseed, subgroup 20A Quinclorac + its methyl ester Quinclorac + its methyl ester

Other Primary Crops Quinclorac + its methyl ester Quinclorac

Rotational Crop Quinclorac+ its methyl ester Quinclorac

Livestock

Ruminant Quinclorac Quinclorac

Poultry Quinclorac Quinclorac

Drinking Water Quinclorac Not Applicable

5.2. Food Residue Profile

D397719, D404569, D404912, S. Hummel, G. Otakie, 9/6/12

D402192, S. Hummel, 5/1/13

Residue Field Trials. The available field trial data on canola are adequate to support use of the 

quinclorac (acid) DF formulation. Additional data may be needed before the use of a quinclorac 

dimethyl amine formulation is supported.

Meat, Milk, Poultry, and Eggs: Adequate cattle and poultry feeding studies are available. The 

uses proposed in this petition will not affect the existing tolerances on meat, milk, poultry and 

eggs. 

Crop Field Trials:

Seventeen field trials for quinclorac DF on canola were conducted in Canada (16 trials) and the 

United States (1 trial), encompassing Zone 5 (MB; 1 trial), 7 (ND, US; one trial) and 14 (AB; 5 

trials, SK; 7 trials; MB; 4 trials) during the 1997 growing season. A single broadcast spray

application at a target rate of 100 g ae/ha/season. Mature canola seed were harvested at 
Page 27 of 59

preharvest intervals (PHIs) of 60 days. In two trials, samples were collected at different time 

intervals (PHIs of 53, 60, 67, 74 days) to monitor residue decline.

Maximum residues in canola seed were 0.85 ppm for quinclorac, 0.23 ppm for the metabolite 

quinclorac methyl ester and 1.00 ppm for the combined quinclorac residues, when treated at 

~100 g a.e./ha/season and harvested at a PHI of 60 days. Due to very low levels of observed 

residues, no decline trend could be determined in canola seed.

Processed Food and Feed

Processing studies were submitted to support use on canola, conducted at a 1x and 5x 

exaggerated rate. The processing data are adequate to support the use of quinclorac on canola. 

Quinclorac residues (including the methyl ester) concentrated 1.5 x in oil but were slightly

reduced in canola meal (0.92x). Quinclorac acid did not concentrate in canola commodities. No 

tolerance is necessary for canola oil, since the HAFT from the field trials (0.9 ppm) when 

multiplied by the concentration factor (1.5x), does not exceed the recommended tolerance for 

residues of quinclorac and its methyl ester on canola seed.

Confined and Field Accumulation in Rotational Crops

Adequate rotational crop studies are available to support the use of quinclorac in the U S. No 

residues greater than the limit of detection of 0.05 ppm quinclorac were found in mustard leaves 

and turnip leaves and roots when planted 120 and/or 270 days after a quinclorac application to 

rice. (The analytical method was validated down to 0.05 ppm, so 0.05 ppm may be called the 

limit of quantitation (LOQ) or the lower limit of method validation (LLMV). Quantifiable 

residues of concern are not expected at rotational crop intervals of 120 days or longer.

5.3. Water Residue Profile

M. Lowit, N. Andrews, D397720, 8/9/12; M. Lowit, N. Andrews, D405093, 9/14/12

A new water assessment was not needed to support tolerances on canola, since there is no 

proposal for U. S. registration. The most recent assessment is performed according to current 

EFED guidance. Screening-level Tier I modeling was used to estimate surface water 

concentrations for use on cranberry (provisional cranberry model) and rice (Tier I rice model). 

The Tier I SCI-GROW model was used to estimate groundwater concentrations for all uses.

Surface water EDWCs recommended for both acute and chronic dietary exposure are 511 μg/L, 

from the Tier I rice model. The recommended groundwater EDWCs are 29 μg/L for both acute 

and chronic exposure. 

5.4 Dietary Risk Assessment

D406419, B. Cropp-Kohlligian, 8/1/2013

Description of Residue Data Used in Dietary Assessment
Page 28 of 59

Acute and chronic aggregate dietary (food and drinking water) exposure and risk assessments 

were conducted using the Dietary Exposure Evaluation Model DEEM-FCID, Version 3.16 which 

uses food consumption data from the U.S. Department of Agriculture’s National Health and 

Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA). This dietary

survey was conducted from 2003 to 2008. These analyses were performed to support the Section 

3 request for quinclorac uses on rhubarb and low growing berry, except strawberry, subgroup 13-

07H and to support Registration Review for quinclorac and the dimethylamine (DMA) salt of 

quinclorac. All registered, pending and proposed uses of quinclorac and the DMA salt of 

quinclorac, as of the date of this memorandum, are included in these assessments. 

Tolerances have been established for quinclorac (40CFR §180.463[a]) in livestock and cereal 

grain commodities. HED has determined that the use of the DMA salt of quinclorac on cereal 

grains will not affect the established tolerances for quinclorac on rice, grain sorghum, and wheat.

The residue of concern (ROC), for both tolerance enforcement and risk assessment, is the parent 

compound, quinclorac for the commodities registered n the U. S. However, quinclorac and its

methyl ester are the residues of concern in canola.

The quinclorac drinking water estimates used in these dietary risk assessments were provided by 

EFED (DP# 397720, M. Lowit/N. Andrews, 8/9/12 and DP# 405093, M. Lowit/N.Andrews, 

9/14/12), and incorporated directly into the dietary assessments. Water residues were 

incorporated in DEEM-FCID via entry into the food categories “water, direct, all sources” and 

“water, indirect, all sources.” The estimated drinking water concentrations (EDWCs) from 

existing and proposed uses of quinclorac for both acute and chronic scenarios in ground and 

surface water are 0.029 ppm and 0.511 ppm, respectively. 

Rice (labeled for a single application of 0.5 lb ai/A) was identified as the use resulting in the 

highest EDWCs for surface water. Because the use on rice involves flooding (for which the 

current Tier II model is not parameterized), the surface water EDWCs were assessed using a Tier 

I Rice Model, Version 1.0 (May 8, 2007). Turf grass was identified as the use resulting in the 

highest EDWCs for ground water. The EDWC in ground water was assessed using the Tier I 

Screening Concentration in Ground Water (SCI-GROW, Version 2.3) model. These models, and 

their descriptions, are available at the EPA internet website via the web link, 

http://www.epa.gov/oppefed1/models/water/. No surface or ground water monitoring data were 

available for quinclorac. 

Percent Crop Treated Used in Dietary Assessment

The acute and chronic assessments are based on the assumption that 100% of all commodities 

with tolerances will be treated.

Acute Dietary Risk Assessment

The acute dietary assessment is highly conservative, and assumes 100% crop treated (%CT), 

along with tolerance-level residues for all agricultural commodities. It used DEEM default 

processing factors and an empirical processing factor for oil commodities of Rapeseed Subgroup 
Page 29 of 59

20A. In addition, Tier I drinking water estimates were used. Tier I modeling was used to 

estimate drinking water concentrations.

The acute (food + water) dietary risk estimate at the 95th percentile of exposure is 1.6% of the 

acute population adjusted dose (aPAD) for females age 13 to 49. This is the only population 

subgroup for which an acute endpoint was selected. 

Generally, the Agency is concerned when risk estimates exceed 100% of the PAD. The acute 

dietary risk estimate for quinclorac is below HED’s level of concern. 

Chronic Dietary Risk Assessment

The chronic dietary assessment is highly conservative, and assumes 100% crop treated (%CT), 

along with tolerance-level residues for all agricultural commodities. Default processing factors 

from DEEM 7.81 were used (for dried beef and cranberry juice) in the analyses. Tier I modeling 

was used to estimate drinking water concentrations.

The chronic (food + water) dietary risk estimates are less than or equal to 8.9% of the chronic 

population adjusted dose (cPAD) for all population subgroups. All Infants < 1 year of age is the 

most highly-exposed subgroup, utilizing 8.9% of the cPAD, while the general US population 

utilizes 3.6% of the cPAD. 

Generally, the Agency is concerned when risk estimates exceed 100% of the PAD. All chronic 

dietary risk estimates for quinclorac are below HED’s level of concern. 

Cancer Dietary Risk Assessment

Quinclorac was classified in 1992 by the HED Cancer Peer Review committee (CPRC) as a 

group D carcinogen - not classifiable as to human carcinogenicity- based on recommendation by

the EPA Scientific Advisory Panel (TXR# 0010416). This classification was based on equivocal 

increase in the incidence of one type of benign tumor (pancreatic acinar cell adenomas) in only

one sex and one species of animals (male Wistar rats). Quantification of risk using the chronic 

RfD will adequately account for all chronic effects, including carcinogenicity, that may result 

from exposure to quinclorac.
Page 30 of 59

Table 5.4.6. Summary of Dietary (Food and Drinking Water) Exposure and Risk for

Quinclorac

Population Subgroup

Acute Dietary

(95th Percentile) Chronic Dietary Cancer

Dietary 

Exposure 

(mg/kg/day)

% aPAD*

Dietary 

Exposure

(mg/kg/day)

% cPAD*

Dietary 

Exposure

(mg/kg/day)

Risk

General U.S. Population

N/A N/A

0.013728 3.6

N/A N/A

All Infants (< 1 year old) 0.033999 8.9

Children 1-2 years old 0.023500 6.2

Children 3-5 years old 0.019280 5.1

Children 6-12 years old 0.013431 3.5

Youth 13-19 years old 0.010195 2.7

Adults 20-49 years old 0.013614 3.6

Adults 50+ years old 0.012525 3.3

Females 13-49 years old 0.032207 1.6 0.012893 3.4
Page 31 of 59

6.0. Residential (Non-Occupational) Exposure/Risk Characterization

Ivan Nieves, D404915, D404797, 9/18/12 

Although this document addresses proposed new agricultural uses outside of the U. S., which do 

not involve applications by homeowners or commercial applicators in residential settings, HED 

has recently updated the residential exposure standard operating procedures (SOPs) and body

weights to be used in all human health assessments as well as the incorporation of new chemical 

specific toxicological information. As a result of the updated policies and parameters, all of the 

existing residential (non-occupational) use patterns have been reassessed in this document 

because these scenarios will impact the quinclorac aggregate assessment.

Although, quinclorac products do not appear to be specifically marketed towards residential 

handler use (i.e., homeowners); a residential handler assessment was performed to be protective 

of any such use. Quinclorac is currently registered for use on turf grass (lawns, sod, turf areas) 

including but not limited to grounds or lawns around residential and commercial establishments, 

multifamily dwellings, military and other institutions, parks, airports, roadsides, schools, picnic 

grounds, athletic fields, houses of worship, cemeteries, golf courses, prairie grass areas, and sod 

farms. Quinclorac may also be used in and around established landscape ornamentals and 

ornamental gardens. The quinclorac products used in residential settings can be formulated as 

granular, liquid, and dry flowable formulations. 

6.1. Residential Handler Exposure

Based on the anticipated use patterns and current labeling, types of equipment and techniques 

that can potentially be used, residential handler exposure is expected from the existing uses. The 

quantitative exposure/risk assessment developed for residential handlers is based on the 

following scenarios: 

1. Loading/Applying granules for belly grinder,

2. Loading/Applying granules for push type rotary spreader,

3. Loading/Applying granules for a spoon;

4. Loading/Applying granules for a cup and shaker can;

5. Applying granules by hand;

6. Mixing/loading/applying liquid and dry flowable formulations via manually-pressurized handwand, a hoseend sprayer, a backpack, and a sprinkler can; 

7. Mixing/loading/applying ready-to-use formulation via a trigger sprayer, and a hose-end sprayer.

For residential handlers, HED presents exposure estimates for individuals wearing shorts, shortsleeved shirts, shoes plus socks. Pesticide application area assumed to be performed by adults 

only, however the assessment does group 16 year olds with adults. 

Table 6.1 lists the exposures and risk estimates for the residential handler scenarios. The updated 

exposure scenarios result in risk estimates that do not exceed HED’s level of concern (MOEs ≥ 

100).
Page 32 of 59

Table 6.1. Quinclorac Residential (Non-Occupational) Handler Estimated Risks

Formulation Application 

Equipment/Method Application Rate1 Units

Area 

Treated or

Amount 

Handled 

Daily

Units (per 

day)

Inhalation 

Unit 

Exposure 

(mg/lb ai)2

Inhalation 

Exposure 

(mg/day)

Inhalation 

Absorbed 

Dose3

(mg/kg/day)

Inhalation 

MOE4

Granule

Push-type spreader 0.68 lb ai/acre 0.5 acres 0.0026 0.00088 0.000011 6,300,000

Belly grinder

0.0000172 lb ai/ft2

1200 ft20.039 0.0008 0.00001 7,000,000

Spoon

100 ft2

0.087 0.00015 0.0000019 37,000,000

Cup; Shaker can 0.013 0.000022 0.00000028 250,000,000

Hand dispersal 0.38 0.00065 0.0000082 8,600,000

Liquid 

concentrate

Hose-end Sprayer 0.78 lb ai/acre 0.5 acres 0.022 0.0086 0.00011 650,000

Manually-pressurized 

handwand 0.16 lb ai/gallon 5 gallons 0.018 0.014 0.00018 390,000

Backpack 0.14 0.11 0.0014 50,000

Sprinkler can 0.0000172 lb ai/ft21000 ft20.022 0.00038 0.0000047 15,000,000

Trigger-sprayer

(Ready-to-Use) 0.0172 lb ai/bottle 1 bottle 0.061 0.001 0.000013 5,300,000

Hose-end Sprayer

(Ready-to-Use) 0.76 lb ai/acre 0.5 acres 0.034 0.013 0.00016 430,000

Waterdispersible 

Granule / Dry 

Flowable

Manually-pressurized 

handwand 0.28 lb ai/gallon 5 gallons 1.1 1.5 0.019 3,600

Hose-end Sprayer 1.4 lb ai/acre 0.5 acres 0.022 0.015 0.00019 360,000

Backpack 0.28 lb ai/gallon 5 gallons 1.1 1.5 0.019 3,600

Sprinkler can 0.0000172 lb ai/ft21000 ft20.022 0.00038 0.0000047

1. Max application rate based on various labels containing non-occupational use sites registered for quinclorac

2. Based on Standard Operating Procedures for Residential Pesticide Exposure Assessment http://www.epa.gov/pesticides/science/EPA-OPPHED_Residential%20SOPS_Feb2012.pdf : 

3. Inhalation Dose (mg/kg/day) = daily unit exposure (mg/lb ai) * application rate (lb ai/acre) * amount handled (acres) * inhalation absorption (100%) / body weight (79.5 

kg); 

4. Inhalation MOE = PoD (NOAEL of 70 mg/kg/day) / Daily inhalation dose (mg/kg/day). Level of concern = 100. 
Page 33 of 59

6.2. Residential Post-Application Exposure

There are no proposed residential uses at this time; however, there are existing registered 

residential uses on lawns and turf for liquid and granular formulations that have been reassessed 

as part of Registration Review. A summary of the exposure and risk is provided below for use in 

performing an aggregate exposure assessment.

6.2.1. Residential (Non-occupational) post-application inhalation

Based on the Agency's current practices, a quantitative residential post-application inhalation 

exposure assessment was not performed for quinclorac at this time primarily because 

quinclorac’s vapor pressure (2.7 x 10-7 mm Hg @ 25.0°C) and Henry's Law Constant (3.72 X 10-

2

Pa m3/mol-1) indicate that the compound is relatively non-volatile under field conditions. The 

Agency sought expert advice and input on issues related to volatilization of pesticides from its 

Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in 

December 2009. The Agency received the SAP’s final report on March 2, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The Agency is in the 

process of evaluating the SAP report and may, as appropriate, develop policies and procedures to

identify the need for and, subsequently, the way to incorporate post-application inhalation 

exposure into the Agency's risk assessments. If new policies or procedures are put into place, the 

Agency may revisit the need for a quantitative post-application inhalation exposure assessment 

for quinclorac.

6.2.2. Residential (Non-Occupational) Post-Application Dermal and 

Incidental Oral

Post-application short-term dermal and incidental oral exposure is expected from quinclorac 

treated turf in residential settings (i.e., lawns). Dermal exposures were not quantified due to a 

lack of a dermal toxicological endpoint. Incidental oral exposure risk estimates were calculated 

for hand-to-mouth, object-to-mouth, and soil ingestion exposures for 1 to <2 year old children 

playing in the treated turf. Even though there is a granular product, an assessment for episodic 

granular ingestion was not done since there is no applicable endpoint (i.e., no acute dietary point 

of departure for children).
Page 34 of 59

Table 6.2. Short-Term Oral Non-dietary Ingestion Residential Post-application Exposure and Risk Estimates 

for Quinclorac Resulting from Application to Turf

Lifestage Post-application Exposure 

Scenario

Application 

Rate a

(lb ai/A)

TTRb

(ug/cm2)

Oral Dose c, d, e

(mg/kg/day)

Oral 

MOEsf

Liquids

Child 1 < 2 year old Oral 

Hand-to-Mouth

1.4 0.16

0.021 3,300

Object-to-Mouth 0.00065 110,000

Soil Ingestion 4.7E-05 1,500,000

Granular

Child 1 < 2 year old Oral 

Hand-to-Mouth

0.68 0.015

0.0010 68,000

Object-to-Mouth 0.000063 1,100,000

Soil Ingestion 2.3E-05 3,000,000

a. Application rates = maximum application rates from latest LUIS report current as of 7/19/2012.

b. Turf Transferable Residue (TTR) (Not Chemical Specific) = AR*FAR ((1-FD)

t

)* 4.5x108 [ug/lb]*2.5-8[acre/cm2]

c. Hand-to-Mouth Dose (mg/kg/day) = E = [HR * (FM * SAH) * (ET * N_Replen) * (1- (1- SE)

(Freq_Replen/N-Replens))]

d. Object-to-Mouth Dose (mg/kg/day) = E = [OR* CF1 * SAMO * (ET * N_Replen) * (1- (1- SEO)

(Freq_Replen/N_Replen))]

e. Soil Ingestion Dose (mg/kg/day) = E = SRt * SIgR * CF1

f. Oral MOE = NOAEL (70 mg/kg/day) / Oral Dose (mg/kg/day)

6.3. Combined Residential Risk Estimates (Multiple Exposure Scenarios)

HED combines risk values resulting from separate exposure pathways when it is likely they can 

occur simultaneously based on the use pattern, the behavior associated with the exposed 

population, and the hazard associated with the points of departure. HED reviewed all residential 

sources of exposure to determine which residential exposure scenarios would be appropriate to 

combine with dietary exposure for an aggregate risk assessment. The only applicable exposure 

pathways are inhalation (for adult handlers) and incidental oral (for post-application exposure to 

children). For children, the incidental oral scenarios (i.e., hand-to-mouth, object-to-mouth, and 

soil ingestion) should be considered inter-related and it is likely that they occur interspersed 

amongst each other across time. Combining these scenarios together would be overlyconservative because of the conservative nature of each individual assessment. 

6.4. Residential Risk Estimates for Use in Aggregate Assessment

Table 6.4 reflects the residential risk estimates that are recommended for use in the aggregate 

assessment for quinclorac.

 The recommended residential exposure for use in the adult aggregate assessment reflects inhalation 

exposure from residential handlers mixing/loading/applying water-dispersible granule/dry flowable 

formulations with a manually-pressurized handwand and/or backpack equipment.

 The recommended residential exposure for use in the children 1<2 years old aggregate assessment reflects 

hand-to-mouth exposures from post-application exposure to treated turf.
Page 35 of 59

Table 6.4. Residential Risk Estimates for Use in the Quinclorac Aggregate Assessment

Lifestage / Exposure Scenario Dose MOE

Adults – Residential Handler M/L/A, Water-dispersible Granule/Dry Flowable, ManuallyPressurized Handwand and/or Backpack 0.019 3,600

Children 1 < 2 Years Old - Turf (Liquids), Hand-to-Mouth 0.021 3,300

6.5. Residential Bystander Post-application Inhalation Exposure

Based on the Agency's current practices, a quantitative post-application inhalation exposure 

assessment was not performed for quinclorac at this time primarily because of the low acute 

inhalation toxicity (Toxicity Category III and IV), low vapor pressure 2.7 x 10-7 mm Hg @ 

25.0°C, and the low proposed use rates. However, volatilization of pesticides may be a source of 

post-application inhalation exposure to individuals nearby pesticide applications. The Agency

sought expert advice and input on issues related to volatilization of pesticides from its Federal 

Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, 

and received the SAP’s final report on March 2, 20101. The Agency is in the process of 

evaluating the SAP report and may, as appropriate, develop policies and procedures to identify

the need for and, subsequently, the way to incorporate post-application inhalation exposure into 

the Agency's risk assessments. If new policies or procedures are developed, the Agency may

revisit the need for a quantitative post-application inhalation exposure assessment for quinclorac.

6.6. Spray Drift

Spray drift is always a potential source of exposure to residents nearby to spraying operations. 

This is particularly the case with aerial application (a method proposed to be employed for 

quinclorac), but, to a lesser extent, could also be a potential source of exposure from the ground 

application method also employed for quinclorac. The Agency has been working with the Spray

Drift Task Force, EPA Regional Offices and State Lead Agencies for pesticide regulation and 

other parties to develop the best spray drift management practices. On a chemical by chemical 

basis, the Agency is now requiring interim mitigation measures for aerial applications that must 

be placed on product labels/labeling. The Agency has completed its evaluation of the new 

database submitted by the Spray Drift Task Force, a membership of U.S. pesticide registrants, 

and is developing a policy on how to appropriately apply the data and the AgDRIFT computer 

model to its risk assessments for pesticides applied by air, orchard airblast and ground hydraulic 

methods. After the policy is in place, the Agency may impose further refinements in spray drift 

management practices to reduce off-target drift with specific products with significant risks 

associated with drift.

Although a quantitative residential post-application inhalation exposure assessment was not 

performed as a result of pesticide drift from neighboring treated agricultural fields, an inhalation 

exposure assessment was performed for flaggers. This exposure scenario is representative of a 

 

1

Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html
Page 36 of 59

worse case inhalation (drift) exposure and may be considered protective of most outdoor 

agricultural and commercial post-application inhalation exposure scenarios. 

7.0. Aggregate Exposure/Risk Characterization

In accordance with the FQPA, HED must consider and aggregate (add) pesticide exposures and 

risks from three major sources: food, drinking water, and residential exposures. In an aggregate 

assessment, exposures from relevant sources are added together and compared to quantitative 

estimates of hazard (e.g., a NOAEL or PAD), or the risks themselves can be aggregated. When 

aggregating exposures and risks from various sources, HED considers both the route and 

duration of exposure.

7.1. Acute Aggregate Risk

In examining acute aggregate risk, HED has assumed that the only pathway of exposure relevant 

to the acute time frame is dietary exposure. Therefore, the acute aggregate risk is comprised on 

exposures to quinclorac residues in food and drinking water and is equivalent to the acute dietary

risk estimates summarized in Table 5.4.6 in Section 5.4.3. The acute dietary risk estimates are 

well below HED’s level of concern for Females 13-49 years old.

7.2. Short-Term Aggregate Risk

In examining short-term aggregate risk, HED reviewed all residential sources of exposure to 

determine which residential exposure scenarios would be appropriate to combine with dietary

exposure for an aggregate risk assessment. The only applicable exposure pathways are 

inhalation (for adult handlers) and incidental oral (for post-application exposure to children). For 

children, the incidental oral scenarios (i.e., hand-to-mouth, object-to-mouth, and soil ingestion) 

should be considered inter-related and it is likely that they occur interspersed amongst each other 

across time. Combining these scenarios together would be overly-conservative because of the 

conservative nature of each individual assessment. The recommended residential exposure for 

use in the adult aggregate assessment reflects inhalation exposure from residential handlers 

mixing/loading/applying water-dispersible granule/dry flowable formulations with a manuallypressurized handwand and/or backpack equipment. The recommended residential exposure for 

use in the children 1<2 years old aggregate assessment reflects hand-to-mouth exposures from 

post-application exposure to treated turf.
Page 37 of 59

The Aggregate MOEs are above the LOC of 100 and are not of concern (Table 7.2).

Table 7.2 Short-Term Aggregate Risk Calculations

Population

Short-Term Scenario

NOAEL

mg/kg/day LOC1

Max 

Allowable 

Exposure

2

mg/kg/day

Average 

Food and 

Water

Exposure 

mg/kg/day

Residential 

Exposure 

mg/kg/day3

Total 

Exposure 

mg/kg/day4

Aggregate 

MOE (food, 

water, and 

residential)5

Adult males and 

female –

Residential 

Handler M/L/A, 

Water-dispersible 

Granule/Dry 

Flowable, 

ManuallyPressurized 

Handwand and/or 

Backpack1

70 100 0.70 0.013728 0.019 0.032728 2100

Child 1< 2 years 

old – Turf 

(Liquids) Hand-toMouth2

70 100 0.70 0.023500 0.021 0.044500 1600

1 The LOC of 100 includes the standard inter- (10x) and intra- (10x) species uncertainty factors totaling 100, as well 

as an FQPA SF of 1x.)

2 Maximum Allowable Exposure (mg/kg/day) = NOAEL/LOC

3 Residential Exposure = [Oral exposure + Inhalation Exposure]. (Source: Table 6.4, Section 6.4).

4 Total Exposure = Avg Food & Water Exposure + Residential Exposure)

5 Aggregate MOE = [NOAEL / (Avg Food & Water Exposure + Residential Exposure)]

7.3. Intermediate-Term Aggregate Risk

Intermediate-term aggregate exposure takes into account intermediate-term residential exposure 

plus chronic exposure to food and water (considered to be a background exposure level). An 

intermediate-term adverse effect was identified, however, quinclorac is not registered for any use 

patterns that would result in intermediate-term residential exposure; therefore, an intermediateterm aggregate risk assessment was not performed nor required. 

7.4. Chronic Aggregate Risk

In examining chronic aggregate risk, HED has assumed that the only pathway of exposure 

relevant to the chronic time frame is dietary exposure. Therefore, the chronic aggregate risk is 

comprised of exposures to quinclorac residues in food and drinking water and is equivalent to the 

chronic dietary risk estimates summarized in Table 5.4.6 in Section 5.4.4. The chronic risk 

estimates are below HED’s level of concern for all population subgroups. 

7.5. Cancer Aggregate Risk

HED has concluded that assessments using a non-linear approach (e.g. a chronic RfD-based 

approach) will adequately account for all chronic toxicity, including carcinogenicity that could 
Page 38 of 59

result from exposure to quinclorac. Chronic aggregate risk estimates are below HED’s level of 

concern, therefore, cancer risk is also below HED’s level of concern. 

7.6. Cumulative Exposure/Risk Characterization

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 as 

to quinclorac and any other substances and quinclorac does not appear to produce a toxic 

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

EPA has not assumed that quinclorac has 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/.

8.0. Occupational Exposure/Risk Characterization

There are no U. S. registered agricultural uses associated with the proposed new use on rapeseed 

subgroup 20A. This section is not applicable.

9.0. References

Cropp-Kohlligian, B. 8/1/2013 Quinclorac and the Dimethylamine (DMA) Salt of Quinclorac. 

Acute and Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk 

Assessments for the proposed use on Rapeseed subgroup 20A. D406419 

Greear, W. and Rinde, E. 8/26/1992. Second Carcinogenicity Peer Review of Quinclorac. TXR 

No. 0010416.

Lowit, M. and Andrews, M. 8/9/2012. Quinclorac: Drinking Water Assessment to Support 

Proposed New Use on Rhubarb and Low Growing Berries Except Strawberry (subgroup 13-

07H). D397720. 

Hummel, S. 9/30/2013. Quinclorac on Rapeseed Subgroup 20A, PP# 1E7957. Summary of 

Analytical Chemistry and Residue Data. D402192, D412463.

Kidwell, J. 11/6/2012. PP# 8F7442. Human Health Risk Assessment for Quinclorac New Use on 

Pasture/Rangeland. D359759.

Nieves, I. 9/18/2012. Quinclorac: Occupational and Residential Exposure/Risk Assessment for 

Registration Review and for Proposed Uses on Rhubarb and Cranberry (and other Low Growing 

Berries in Subgroup 13-07H, except strawberry). D404915, D404797.

Shah, PV and Rowland, J. 8/4/1998. Quinclorac – Report of the Hazard Identification 

Assessment Review Committee. HED Doc. No. 012717.
Page 39 of 59

Tarplee, B. 10/14/1998. Quinclorac – Report of the FQPA Safety Factor Committee. TXR No. 

0012902.

Van Alstine, J. 9/2012. Quinclorac: Summary of Hazard and Science Policy Council (HASPOC) 

Meeting of June 21, 2012: Recommendations on the need for a neurotoxicity Battery Study and 

a DNT study. TXR #: 0056385
Page 40 of 59

Appendix A. Toxicology Profile and Executive Summaries

9.1. A.1Toxicology Data Requirements

The requirements (40 CFR 158.340) for [Type of Use (e.g., food vs. non food)] for [CHEMICAL NAME] are in 

Table 1. Use of the new guideline numbers does not imply that the new (1998) guideline protocols were used.

Test Technical

Required Satisfied

870.1100 Acute Oral Toxicity........................................................

870.1200 Acute Dermal Toxicity...................................................

870.1300 Acute Inhalation Toxicity...............................................

870.2400 Primary Eye Irritation....................................................

870.2500 Primary Dermal Irritation ..............................................

870.2600 Dermal Sensitization......................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent)...............................................

870.3150 Oral Subchronic (nonrodent).........................................

870.3200 21-Day Dermal ..............................................................

870.3250 90-Day Dermal ..............................................................

870.3465 21-/90-Day Inhalation....................................................

yes

yes

yes

no

no2

yes

yes1

yes

-

-

870.3700a Developmental Toxicity (rodent)...................................

870.3700b Developmental Toxicity (nonrodent).............................

870.3800 Reproduction .................................................................

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent) ..............................................

870.4100b Chronic Toxicity (nonrodent) ........................................

870.4200a Oncogenicity (rat)..........................................................

870.4200b Oncogenicity (mouse)....................................................

870.4300 Chronic/Oncogenicity....................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.5100 Mutagenicity—Gene Mutation - bacterial.....................

870.5300 Mutagenicity—Gene Mutation - mammalian................

870.5375 Mutagenicity—Structural Chromosomal Aberrations...

870.5900 Mutagenicity—Other Genotoxic Effects.......................

yes

yes

yes

yes

yes

yes

yes

yes

870.6100a Acute Delayed Neurotox. (hen) .....................................

870.6100b 90-Day Neurotoxicity (hen)...........................................

870.6200a Acute Neurotox. Screening Battery (rat)........................

870.6200b 90-Day Neuro. Screening Battery (rat)..........................

870.6300 Develop. Neuro..............................................................

no

no

no3

no3

no3

-

-

-

-

-

870.7485 General Metabolism ......................................................

870.7600 Dermal Penetration........................................................

870.7800 Immunotoxicity .............................................................

yes

-

yes

yes

-

yes

1 The data requirement for a dog 90-day subchronic oral toxicity is satisfied by the dog 1-year chronic oral study.

2 waived (D376603, TXR 0055511)

3 waived (HASPOC, TXR 0056385)
Page 41 of 59

9.2.A.2Toxicity Profiles

Table A.2.1 Acute Toxicity Profile – Quinclorac

Guideline 

No.

Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral - rat 41063505

(1989)

LD50 >2610 mg/kg III 

870.1100 Acute oral - rat 41063506

(1983)

LD50 (male) = 3060 mg/kg

LD50 (female) = 2190 mg/kg

LD50 (combined) = 2680 

mg/kg

III

870.1100 Acute oral - mouse 41063507

(1986)

LD50 >5000 mg/kg IV

870.1200 Acute dermal - rat 41063509

(1983)

LD50 > 2000 mg/kg III

870.1300 Acute inhalation - rat 41063510

(1985)

LC50 > 5.2 mg/L

(4 hr exposure)

III

870.2400 Acute eye irritation –

rabbit

41063511

(1983)

Mild irritant reversible by 

day 8

III

870.2500 Acute dermal irritation –

rabbit

41063512

(1983)

Not an irritant III

870.2600 Skin sensitization –

guinea pig

40573301

(1986)

Dermal sensitizer n/a
Page 42 of 59

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile – Quinclorac

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.3100 90-Day oral 

toxicity (Wistar rat)

41063516 (1986)

Unacceptable/nonguideline based on lack 

of analyses of diet 

concentration, 

homogeneity, stability.

0, 1000, 4000 or 12,000 

ppm in diet

M: 0, 76.8, 302, 930 

mg/kg/day

F: 0, 86.7, 358, 1035 

mg/kg/day

NOAEL = 302 mg/kg/day (males) and 358 

mg/kg/day (females)

LOAEL = 930 mg/kg/day (males) and 1035 

mg/kg/day (females) based on decreased body 

weight gain, food consumption and increased 

water intake in males and females; increased 

SGOT, SGPT and focal chronic interstitial 

nephritis in males.

870.3100 90-Day oral 

toxicity 

(B6C3F1/Crl Br 

mouse)

41063519 (1988)

Acceptable/guideline

when considered together 

with 41063519

0 or 500 ppm in diet

0 or 75 mg/kg/day

NOAEL = 75 mg/kg/day (HDT)

LOAEL was not established in this study (> 75 

mg/kg/day)

870.3100 90-Day oral 

toxicity 

(B6C3F1/Crl Br 

mouse)

41063518 (1986)

Acceptable/guideline 

when considered together 

with 41063518

0, 4000, 8000 or 16,000 

ppm in diet

M: 0, 1000, 2202 or 4555 

mg/kg/day 

F: 0, 1467, 2735 or 5953 

mg/kg/day

NOAEL not established in this study (<1000 

mg/kg/day)

LOAEL = 1000 mg/kg/day (males) and 1467 

mg/kg/day (females), based on decreased body 

weight gains. 

870.3200 21-Day dermal 

toxicity (New 

Zealand White 

rabbit)

44342905 (1990)

Acceptable/guideline

0, 200 or 1000 mg/kg/day 

applied to skin daily for 

21 days.

NOAEL = 1000 mg/kg/day (limit dose)

LOAEL not established in this study (> 1000 

mg/kg/day).

870.3700a Prenatal 

developmental in 

(Wistar rat)

41063524 (1987)

Acceptable/guideline

0, 24.4, 146 or 438 

mg/kg/day (gavage)

Maternal NOAEL = 146 mg/kg/day

LOAEL = 438 mg/kg/day based on increased 

mortality, decreased food consumption and 

increased water consumption.

Developmental NOAEL ≥438 mg/kg/day

LOAEL not established in this study (> 438 

mg/kg/day).
Page 43 of 59

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile – Quinclorac

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.3700b Prenatal 

developmental in 

(Himalayan rabbit)

41063525 (1986), 

41680501 (1990)

Acceptable/guideline

0, 70, 200 or 600 

mg/kg/day (gavage)

Maternal NOAEL = 70 mg/kg/day

LOAEL = 200 mg/kg/day based on decreased 

body weight gain and food consumption (and 

increased water consumption).

Developmental NOAEL = 200 mg/kg/day

LOAEL = 600 mg/kg/day based on increased 

resorption rate, postimplantation loss, 

decreased live fetuses and reduced fetal body 

weight.

870.3800 Reproduction and 

fertility effects

(Wistar rat)

41063526 (1988); 

41874201, -02 (1991, 

1988); 41910001 (1991)

Acceptable/guideline

0, 1000, 4000 or 12,000 

ppm in diet

0, 40, 160 or 480 

mg/kg/day

Parental/Systemic NOAEL = 160 mg/kg/day

LOAEL = 480 mg/kg/day based on reduced 

body weight in both sexes during premating 

and lactation periods.

Reproductive NOAEL = 480 mg/kg/day

LOAEL not established in this study (> 480 

mg/kg/day).

Offspring NOAEL = 160 mg/kg/day

LOAEL = 480 mg/kg/day based on decreased 

pup weight, developmental delays and possible 

marginal effect on pup viability.

870.4300 Combined chronic 

toxicity/ 

carcinogenicity

(Wistar rat)

41063522 (1988); 

42012901, -02 (1991)

Acceptable/guideline

0, 1000, 4000, 8000 or 

12,000 ppm in diet

M: 0, 56, 186, 385 or 487 

mg/kg/day

F: 0, 235, 478 or 757 

mg/kg/day

NOAEL = 385 mg/kg/day (males and 478 

mg/kg/day (females)

LOAEL = 487 mg/kg/day (males) based on 

increased incidence of pancreatic acinar cell 

hyperplasia and 757 (females) based on 

decreased body weight.

Equivocal increase in pancreatic acinar cell 

adenomas in males.

870.4100b Chronic toxicity 

(Beagle dog)

41123201 (1987)

Acceptable/guideline

0, 1000, 4000 or 12,000 in 

diet

M: 0, 34, 142 or 513 

mg/kg/day

F: 0, 35, 140 or 469 

mg/kg/day

NOAEL = 142 mg/kg/day (males) and 140 

mg/kg/day (females)

LOAEL = 513 mg/kg/day (males) and 469 

mg/kg/day (females) based on decreased body 

weight gain and food efficiency, increased liver 

and kidney weights, decreased HgB, RBC, 

MCH and MCV and kidney degeneration.

870.4200 Carcinogenicity

(B6C3F1/Crl Br 

mouse)

41063523 (1988)

Acceptable/guideline

0, 250, 1000, 4000 or 

8000 ppm in diet

M: 0, 37.5, 150, 600 or 

1200 mg/kg/day

NOAEL = 37.5 mg/kg/day

LOAEL = 150 mg/kg/day based on decreased 

body weight in males and females.

No evidence of carcinogenicity.
Page 44 of 59

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile – Quinclorac

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870. 5100 Bacterial reverse 

gene mutation

Ames assay S. 

typhimurium

41063527 (1984)

Acceptable/guideline

Dose range 0 to 5000 

μg/plate with and without 

S9

Negative up to the limit dose (5000 μg/plate) 

with or without S9 in S. typhimurium strains

TA98, TA100, TA1535, TA1537

870.5100 Bacterial reverse 

gene mutation

S. 

typhimurium/E.coli

41063528 (1988) 

Acceptable/guideline

Dose range 0 to 5000 

μg/plate with and without 

S9

Negative up to the limit dose (5000 μg/plate) 

with or without S9 in S. typhimurium strains 

TA98, TA100, TA1535, TA1537 and E. coli

strain WP2 uvrA

870.5300 In vitro mammalian 

forward gene 

mutation, CHO 

cells/HGPRT locus

41680503 (1989)

Acceptable/guideline

Dose range 0 to 2150 

μg/mL with or without S9

Negative for gene mutations up to cytotoxic 

doses (2000 μg/mL) with or without S9.

870.5375 In vitro mammalian 

chromosome 

aberration assay, 

human 

lymphocytes

41076103 (1986)

Acceptable/guideline

Dose range 125 to 1500 

μg/mL without S9 and 

250 to 2500 μg/mL with 

S9

Positive for chromosomal aberrations but only 

at cytotoxic concentrations (2000 μg/mL with 

S9 and 1000 μg/mL without S9).

870.5385 Cytogenetics – in 

vivo mouse 

micronucleus assay

41063530 (1989)

Acceptable/guideline

Single gavage doses up to 

1000 mg/kg

Negative in male and female NMRI mice at all 

doses up to limit dose (1000 mg/kg). Mid and 

high dose groups showed clinical signs of 

toxicity (irregular breathing, apathy, 

piloerection) but no toxicity to target cell was 

observed.

870.5550 Unscheduled DNA

synthesis in 

primary rat 

hepatocytes

41063531 (1986)

Acceptable/guideline

Dose range 0 to 1520 

μg/mL

Negative up to cytotoxic dose (1520 μg/mL).

870.7485 Metabolism and 

pharmacokinetics

(rat) -

biodisposition

41063533 (1987)

Acceptable/guideline

Single gavage doses of 15 

or 600 mg/kg of 14Cquinclorac; 14 daily 

gavage doses of unlabeled 

quinclorac following by a 

single dose of 14Cquinclorac

Quinclorac was rapidly absorbed and 

eliminated primarily in the urine (91-98% of 

dose) with small amounts (1-4%) eliminated in 

the feces by day 5 after dosing. No 

radioactivity was detected in exhaled air. 
Page 45 of 59

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile – Quinclorac

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.7485 Metabolism and 

pharmacokinetics

(rat) – Biliary 

excretion studies

41063533 (1987)

Acceptable/guideline

Single gavage doses of 15 

or 600 mg/kg 14Cquinclorac

Biliary excretion was significant (11.5 to 14.5% 

of dose) at 600 mg/kg but was reabsorbed from 

the intestine and eliminated in the urine.

870.7485 Metabolism and 

pharmacokinetics

(rat) – Plasma level 

studies

41063533 (1987)

Acceptable/guideline

Single gavage doses of 

15, 100, 600 or 1200 

mg/kg

Multiple gavage doses of 

15 or 600 mg/kg/day 14Cquinclorac for 7 days.

Mean residues were detected in plasma 30 

minutes postdosing following all dose 

regimens. Quinclorac is poorly metabolized: 

most of radioactivity was the parent compound. 

Peak plasma levels of radioactivity after 7 days 

of dosing at 600 or 1200 mg/kg/day were 

observed between 7 to 48 hrs postdosing.

870.7485 Metabolism and 

pharmacokinetics

(rat) – Tissue level 

studies

41063533 (1987)

Acceptable/guideline

Multiple gavage doses of 

14C-quinclorac 15 or 1200 

for 7 days.

The highest concentrations of radioactivity in 

tissues were found at 30 minutes after the final 

dose for low and high doses. Significant tissue 

levels were not observed (≤0.45% of dose), 

with highest levels observed in the thyroid, 

bone marrow and adrenal. Tissue levels were 

slightly greater in females.

870.7800 Immunotoxicity

female C57BL/6 J 

Rj mice (8/group) 

48346101 (2010)

Acceptable/guideline

0 (control), 500, 1500, or 

5000 ppm (equivalent to 

0, 176, 439, or 1760 

mg/kg bw/day, for 28 

days

Immunotoxicity NOAEL is 5000 ppm 

(equivalent to 1760 mg/kg/day, the highest dose 

tested and above the limit dose); 

LOAEL was not established.

A.3. Hazard Identification and Endpoint Selection

A.3.1 Acute Reference Dose (aRfD) - Females age 13-49

Study Selected: Developmental toxicity study in rabbits 

MRID No.: 41063525; 41680501

Executive Summary: In a developmental toxicity study (MRID# 41063525), quinclorac (98.3% 

a.i.) was administered to fifteen female Himalayan Rabbits by gavage at dose levels of 0, 70, 

200, or 600 mg/kg/day from gestational days 7–19, inclusive.

Maternal toxicity, observed at 200 mg/kg/day, was manifested as decreased body weight gain 

(36%) and food consumption (13%) during the dosing period. Additional findings noted at 600 

mg/kg/day, included increased water consumption (7% over entire gestation), increased 
Page 46 of 59

incidence of clinical signs (reduced/no defecation, diarrhea, apathy and poor general state) and 

mortality and discoloration of the kidney. The maternal LOAEL is 200 mg/kg/day, based on 

decreased body weight gains and food consumption. The maternal NOAEL is 70 

mg/kg/day.

Developmental toxicity, observed at 600 mg/kg/day consisted of increased rate of resorption and 

post-implantation loss, a decrease in the number of live fetuses, and reduced fetal body weight. 

The NOAEL for developmental toxicity is 200 mg/kg/day.

Dose and Endpoint for Risk Assessment: Developmental NOAEL= 200 mg/kg/day based on 

increased rate of resorption and post-implantation loss, a decrease in the number of live fetuses, 

and reduced fetal body weight at 600 mg/kg/day (LOAEL). 

Comments about Study/Endpoint: The developmental effects are presumed to occur after a 

single exposure (dose) and thus were considered to be appropriate for this (acute) risk 

assessment. This dose/endpoint is applicable only to Female 13 to 49 years old.

Uncertainty Factor (UF): 100 (10 x for inter-species extrapolation and 10x for intra-species 

variability, FQPA SF = 1x).

 

aRfD=

200 mg / kg /day(NOAEL)

100(UF )

= 2.0mg / kg

aPAD=

2 mg / kg /day (aRfD)

1(FQPASF )

= 2.0 mg / kg

A.3.2 Acute Reference Dose (aRfD) - General Population

An endpoint for acute dietary exposure to the general population was not selected because there 

was no single dose endpoint available in the database that was appropriate for this scenario 

A.3.3 Chronic Reference Dose (cRfD) `

Study Selected: Oncogenicity Feeding Study in Mice 

MRID No.: 41063523

Executive Summary: In a carcinogenicity study (MRID# 41063523), B6C3F1/Crl Br mice (60 

sex/dose) were administered via diets with Quinclorac (97.4 or 98.3% a.i) at dose levels of 0, 

250, 1000, 4000, or 8000 ppm (equivalent to 0, 37.5, 150, 600 or 1200 mg/kg/day) for 6 months 

or 78 weeks. Ten mice were terminated at 6 months. The remainders were continued on the test 

material for 18 months.

At the end of 13 weeks, body weights in males and females receiving 8000 ppm were 

significantly lower than controls by 9.6% and 7.4%, respectively. Body weights in males and 

females receiving 1000, 4000, and 8000 ppm for 78 weeks were significantly lower than controls 
Page 47 of 59

(7.9 to 15.9% for males; 14.3 to 17.9 for females. Treatment-related body weight reductions 

compared to controls were also noted in satellite males and females receiving 4000 and 8000 

ppm for 6 months. Absolute liver weights were significantly reduced in male and female mice 

receiving 8000 ppm for 78 weeks, but there was no effect on liver-to-body weight ratio. 

Absolute kidney weights were decreased in males receiving 1000, 4000, and 8000 ppm and in 

females receiving 4000 and 8000 ppm for 78 weeks. Relative kidney weights were decreased in 

males receiving 1000, 4000, and 8000 ppm for 78 weeks. Dose-related increases in relative 

brain weights seen in males and females receiving 1000, 4000, and 8000 ppm. Absolute liver 

weights were also reduced in males receiving 4000 and 8000 ppm for 6 months, while absolute 

kidney weights were reduced in all treated males. A slight decrease in hematocrit values was 

noted in males and females receiving 8000 ppm for 6 months, but not 78 weeks. Effects on other 

hematological parameters were not of biological significance. There was no effect of dosing on 

mortality, food consumption, or clinical signs. The LOAEL is 1000 ppm (150 mg/kg/day) based 

on effects on body weight. The NOAEL is 250 ppm (37.5 mg/kg/day). A maximum tolerated 

dose (MTD) was approached based on decreased body weights in males and females receiving 

8000 ppm.

No evidence of histopathological or neoplastic lesions attributable to administration of any dose 

of Quinclorac was found in any tissue of any mouse.

Dose and Endpoint for Establishing RfD: NOAEL = 37.5 mg/kg/day based on decreased body

weights seen at 150 mg/kg/day (LOAEL).

Comments about Study/ Endpoint: The endpoint selected from the mouse carcinogenicity 

study is appropriate for both the population and the duration of exposure. The NOAEL from this 

study is the lowest NOAEL in the database and therefore protective of all other effects.

Uncertainty Factor(s): 100 (10 x for inter-species extrapolation and 10x for intra-species 

variability; FQPA SF = 1X).

cRfD=

37.5mg / kg /day (NOAEL)

100(UF )

= 0.38 mg / kg / day

cPAD=

0.375 mg / kg / day (cRfD)

1(FQPASF)

= 0.38 mg / kg /day

A.3.4 Incidental Oral Exposure (Short- and Intermediate-Term)

Study Selected: Developmental toxicity study in rabbits. 

MRID Nos.: 41063525; 41680501

Executive Summary: See Appendix A, §870.3700b
Page 48 of 59

Dose and Endpoint for Risk Assessment: Maternal NOAEL= 70 mg/kg/day based on 

decreased body weight gains and food consumption accompanied with increased water 

consumption at 200 mg/kg/day (LOAEL). 

Comments about Study/Endpoint: This endpoint of toxicity occurred after short exposures to 

quinclorac and is suitable for this exposure scenario.

A margin of exposure (MOE) of 100 is applied to account for inter-species extrapolation (10x) 

and for intra-species variability (10x). 

A.3.5 Dermal Exposure (Short-, Intermediate- and Long-Term) 

A dermal endpoint was not selected because an appropriate endpoint was not available (no 

dermal toxicity was seen at the limit dose of 1000 mg/kg/day in a 21-day dermal toxicity study). 

Also, there are no susceptibility concerns.

A.3.6 Inhalation Exposure (Short-, Intermediate- and Long-Term) 

A.3.7 Inhalation Exposure (Short and Intermediate-Term)

Selected Study: Developmental toxicity study in rabbits. 

MRID Nos.: 41063525; 41680501

Executive Summary: See Appendix A, §870.3700b

Dose and Endpoint for Risk Assessment: Maternal NOAEL= 70 mg/kg/day based on 

decreased body weight gains and food consumption accompanied with increased water 

consumption at 200 mg/kg/day (LOAEL). 

Comments about Study/Endpoint: This endpoint of toxicity occurred after short exposures to 

quinclorac and is suitable for this exposure scenario.

A margin of exposure (MOE) of 100 is applied to account for inter-species extrapolation (10x) 

and for intra-species variability (10x).

A.3.7 Inhalation Exposure (Long-Term)

Not applicable. Long-term inhalation exposure is not anticipated under current use scenarios.

 
Page 49 of 59

9.3.A.4Executive Summaries

A.4.1 Subchronic Toxicity

870.3100 90-Day Oral Toxicity - Rat

In a subchronic toxicity study (MRID 41063516), Quinclorac (96.5% a.i.) was administered to 

10 Wistar Chhb-THOM (SPF) rats/sex/dose in diet, at dose levels of 0, 1000, 4000, or 12000 

ppm (0, 76.8, 302.3 or 929.9 mg/kg/day for males and 0, 86.7, 358.0 or 1035.4 mg/kg/day for 

females). There were no deaths occurred. No compound related clinical signs of toxicity were 

observed. The LOAEL is 12,000 ppm (males 929.9 and females 1035.4 mg/kg/day), based on 

decreases in body weight gain, food consumption and an increase in water intake in males and 

females, and decrease in monocytes in female, increases in SGOT and SGPT in males, and 

pathological changes in kidneys of males (slight to minimal focal chronic interstitial nephritis. 

The NOAEL is 4000 ppm (males 302.3 and females 358.0 mg/kg/day). 

This subchronic toxicity study is classified unacceptable/non-guideline due to lack of 

information on the purity of the test material and information on stability and homogeneity of the 

test substance in the diet.

870.3100 90-Day Oral Toxicity - Mouse

In a subchronic toxicity study (MRID 41063518), Quinclorac (98.29% a.i.) was administered to 

10 B6C3F1/Crl BR mice/sex/dose in diet, at dose levels of 0, 4000, 8000, or 16000 ppm (0, 

1000, 2202 or 4555 mg/kg/day for males and 0, 1467, 2735 or 5953 mg/kg/day for females). No 

deaths occurred. No compound related clinical signs of toxicity were observed. At 8000 and 

16000 ppm there was an increase in water intake in males and females and BUN in males. There 

was decreased kidney weight in males and females and relative kidney weight in males in the 

16,000 ppm group. At 4000 ppm there was decreased body weight gain in males and females. 

The LOAEL is 4,000 ppm (males 1,000 and females 1467 mg/kg/day), based on decreases in 

body weight. The NOAEL was not established. 

This subchronic toxicity study is classified Acceptable/non- guideline requirement for a 

subchronic oral study (82-1) in mice. However taken with MRID 41063519, it is acceptable/ 

guideline.

In another subchronic toxicity study (MRID 41063519), Quinclorac (98.29% a.i.) was 

administered to 10 B6C3F1/Crl BR mice/sex/dose in diet, at dose levels of 0 or 500 ppm (75 

mg/kg/day, HDT). No deaths occurred. No compound related clinical signs of toxicity were 

observed. Females in the 500 ppm group had slightly (although statistically significant) reduced 

body weights when compared to controls on day 98. This decrease was minimal and is not 

believed to be compound related since body weights were not significantly different at any other 

time intervals. The NOAEL is 500 ppm (75 mg/kg/day). 

This subchronic toxicity study is classified Unacceptable because only one dose level was tested. 

However taken with MRID 41063518, it is acceptable /guideline.
Page 50 of 59

870.3150 90-Day Oral Toxicity - Dog

The data requirement for a dog 90-day subchronic oral toxicity is satisfied by the 1-year dog 

chronic oral study.

870.3200 21/28-Day Dermal Toxicity – Rabbit

In a twenty-one day dermal toxicity study (MRID 44342905), Quinclorac (98.29% a. I.) in 0.5% 

carboxymethyl cellulose was applied dermally to 5 New Zealand White (KFM) albino 

rabbits/sex/dose at dose levels of 0, 40, 200 and 1000 mg/kg/day for 7 days a week for 3 weeks. 

The hair was clipped from the dorsal surface prior to treatment and once a week during the study.

Test material was applied daily for 3 weeks to an area of skin approximately 10% of the total 

body surface area on the back of each rabbit and covered with a semi-occlusive gauze. After 6 

hour exposure, the excess test material was removed from the treated area with a luke-warm 

water and kept open until next application. Vehicle control group received 2 ml/kg b.w of 0.5% 

carboxymethyl cellulose in water, while test groups received suspension of test material in 

aqueous 0.5% carboxymethyl cellulose (2 ml/kg/b.w). There was no treatment-related clinical 

observations, changes in body weight gain, food consumption, histopathologic findings or 

hematologic or blood chemistry parameters after a 21 day (7 days/week) repeated application of 

Quinclorac at a nominal concentrations of 0, 40, 200 or 1000 mg/kg/day in 0.5% carboxymethyl 

cellulose. The limit dose is 1000 mg/kg/day. No mortality occurred at any dose level tested. No 

local skin irritation was reported during the study. The NOAEL ≥1000 mg/kg/day, Limit Dose, 

(HDT; males and females). The LOAEL >1000 mg/kg/day (HDT; males and females).

This study is classified as Acceptable/Guideline and does satisfy the guideline requirements for a 

21-day repeated dermal toxicity study in rabbits (82-2).

870.3465 90-Day Inhalation – Rat

The requirement of a 28-day inhalation toxicity study was waived based on low volatility, low 

acute inhalation toxicity and large extrapolated inhalation MOE (D376603, 23 September 2010).

A.4.2 Prenatal Developmental Toxicity

870.3700a Prenatal Developmental Toxicity Study - Rat

In a developmental toxicity study (MRID # 41063524), Quinclorac (96.5% a.i.) was 

administered to twenty-five female Wistar rats by gavage at dose levels of 0, 24.4, 146, and 438 

mg/kg/day from gestational days 6-15, inclusive. Maternal toxicity, observed at 438 mg/kg/day, 

was manifested as decreased food consumption (10-15%) and increased water consumption (31-

54%) during the dosing and/or gestation period as well as mortality. The maternal LOAEL is 

438 mg/kg/day, based on decreased food consumption, increased water consumption and 

mortality. The maternal NOAEL is 146 mg/kg/day. No developmental toxicity was observed. 

The LOAEL for developmental toxicity is >436 mg/kg/day. The developmental NOAEL is ≥436 

mg/kg/day.
Page 51 of 59

This study is classified as Acceptable/Guideline and satisfies the guideline requirement for a 

developmental toxicity study in rats.

870.3700b Prenatal Developmental Toxicity Study - Rabbit

In a developmental toxicity study (MRID# 41063525), Quinclorac (98.3% a.i.) was administered 

to fifteen female Himalayan Rabbits by gavage at dose levels of 0, 70, 200, or 600 mg/kg/day

from gestational days 7–19, inclusive. Maternal toxicity, observed at 200 mg/kg/day, was 

manifested as decreased body weight gain (36%) and food consumption (13%) during the dosing 

period. Additional findings noted at 600 mg/kg/day, included increased water consumption (7% 

over entire gestation), increased incidence of clinical signs (reduced/no defecation, diarrhea, 

apathy and poor general state) and mortality and discoloration of the kidney. The maternal 

LOAEL is 200 mg/kg/day, based on decreased body weight gains and food consumption. The 

maternal NOEL is 70 mg/kg/day. Developmental toxicity, observed at 600 mg/kg/day consisted 

of increased rate of resorption and post-implantation loss, a decrease in the number of live 

fetuses, and reduced fetal body weight. The NOAEL for developmental toxicity is 200 

mg/kg/day. This study is classified as Acceptable/Guideline and satisfies the guideline 

requirement for a developmental toxicity study (83-3b) in rabbits.

A.4.3 Reproductive Toxicity

870.3800 Reproduction and Fertility Effects - Rat

In a 2-generation reproduction study (MRID # 41063526), Quinclorac (≥97.3% a.i.) was 

administered to Wistar rats (24/sex/group) at dietary levels of 0, 1,000, 4,000 or 12,000 ppm (0, 

40, 160 or 480 mg/kg/day, respectively).

Parental toxicity: Evidence of toxicity was observed in the parental rats at 12,000 ppm (480 

mg/kg/day). Fl males showed reduced mean body weight during premating, which largely 

reflected their decreased weights as pups at weaning (at week 0, -24%, p<0.0l, becoming less 

pronounced at week 18, -6% below controls, p<0.05). F0 males showed no effects. F0 females 

showed a small but statistically significant decrease in mean body weight at Week 24 of 

premating (-4%, p<0.05) but not at earlier times. F1 females had decreased body weights during 

premating (at Week 18, -12%; p<0.01): as with males, part of the decrease reflected smaller 

weights at weaning. During gestation, decreases of about -6% in mean body weight at Day 20 

were observed for the F0 females in the second mating (p<0.01) and the Fl females in their only 

mating (p<0.05). However, in the second mating of F0 females, there was no significant effect. 

The F0 (first mating only) and Fl females showed reduced body weights during part or all of 

lactation (up to -10% below controls). In addition to body weight changes, an increased 

incidence of interstitial nephritis was observed in F0 and Fl females. The parental systemic 

toxicity LOAEL is 12,000 ppm (480 mg/kg/day), based on decreased body weight during 

premating and lactation. The NOAEL is 4000 ppm (160 mg/kg/day).

Reproductive toxicity: No effects on reproductive parameters were observed. The reproductive 

toxicity NOAEL is 12,000 ppm (480 mg/kg/day). A reproductive toxicity LOAEL was not 

established (>480 mg/kg/day).
Page 52 of 59

Offspring toxicity: At 12,000 ppm (480 mg/kg/day), the major effect on pup growth and 

development was observed during lactation. Decreased pup weights were observed in male and 

female Fl and F2 pups during lactation (at Day 21 of lactation, 15-26% below controls; all 

generations p<0.0 1) and delayed physical development (delayed pinna unfolding and eye 

opening) was also observed. Decreased pup weight at Lactation Day 0 was seen only in the F2

male and female pups (approximately 7% below controls), a dose also associated with a slight 

decrease in maternal weight during gestation. Slightly decreased pup viability and survival were 

reported; however, these effects were marginal (<6%), not seen in all offspring generations and 

did not achieve statistical significance. The relationship to treatment of this finding is considered 

equivocal. The offspring LOAEL is 12,000 ppm (480 mg/kg/day), based on effects on pup 

growth with a possible marginal effect on pup viability. The offspring NOAEL is 4000 ppm (160 

mg/kg/day).

This study is classified as Acceptable/guideline and satisfies the guideline requirement for a 

multigeneration reproductive toxicity study in the rodent (870.3800).

A.4.4 Chronic Toxicity

870.4100a (870.4300) Chronic Toxicity – Rat

The combined chronic/carcinogenicity study satisfies this requirement. 

870.4100b Chronic Toxicity - Dog

In a 1-year feeding study in dogs (MRID 41123201), Quinclorac (97.4% a.i.) was administered 

to groups of 6 male and 6 female beagle dogs at dietary levels of 0, 1000, 4000 or 12000 ppm 

(equivalent to 0, 34, 142, or 513 mg/kg/day for males and 0, 35, 140, or 469 mg/kg/day for 

females) for 12 months. No effect on mortality was observed. Administration of 12000 ppm 

resulted in lower mean body weight, compared with control, reduced body weight gain and an 

adverse effect on food efficiency. There was a marginal reduction of body weight gain and food 

efficiency in male dogs fed 4000 ppm of test substance. In male dogs fed 12000 ppm of test 

substance, there were significant (<0.01) treatment-related reductions in hemoglobin 

concentration, erythrocyte count, and hematocrit, mean corpuscular volume (MCV) and mean 

corpuscular hemoglobin (MCH) values. In females fed 12000 ppm of test substance, significant 

reductions (p <0.05 or p <0.01) were seen in hemoglobin concentration, MCH, and MCV at all 

study intervals (weeks 13, 26, and 52), hematocrit at weeks 26 and 52 and erythrocyte count at 

week 26. In females fed 4000 ppm test substance, significant reductions (p <0.05) were seen at 

week 26 in hemoglobin concentration, erythrocyte count, and hematocrit. Administration of 

12000 ppm of test substance resulted in decreases in a number of clinical chemistry parameters; 

however, significant (p <0.01) changes were noted only for creatinine, calcium, and albumin. 

However, it should be noted that, in most cases, clinical adverse effects are only associated with 

increased values for these parameters. At the 12000 ppm dose level, increase in absolute (p <0.01 

for males) and relative liver weights (p <0.01 for both males and females) were observed for 

both sexes. Relative liver weights also were significantly increased (p <0.05) in females of the 

4000 and 1000 ppm groups. Relative kidney weights were significantly increased (p <0.01) in 
Page 53 of 59

both males and females of the 12000 ppm group and in males of the 4000 ppm group. There 

were no histopathologic correlates to account for the increased organ weights. Histopathologic 

findings in the liver were limited to an increase in focal mononuclear infiltration and to single 

cell necrosis in two dogs in the 12000 ppm group. Hydropic degeneration of the kidney was seen 

in two males and two females of the 12000 ppm group.

The LOAEL is 12000 ppm (513 mg/kg/day-males, 469 mg/kg/day- females) based on the 

reduced body weight gain, adverse effect on food efficiency, hematological and clinical 

chemistry values, increased liver and kidney weights, and microscopic findings. The NOAEL is 

4000 ppm (142 mg/kg/day for males and 140 mg/kg/day for females).

This study is classified as Acceptable/Guideline and satisfies the guideline requirement for a 

feeding study (83-1) in dogs.

A.4.5 Carcinogenicity

870.4200a Carcinogenicity Study - rat

In a combined chronic toxicity/carcinogenicity study (MRID# 41063522), Wistar (chbb-THOM) 

rats (80/sex/group) were administered via diets with Quinclorac (97.4% a.i.) at dose levels of 0, 

1000, 4000, 8000, or 12000 ppm (equivalent to 0, 56, 186, 385, or 487 mg/kg/day for males and 

0, 60, 235, 478, or 757 mg/kg/day for females, respectively). Ten rats/sex/group were terminated 

at 12 months. The remainders were continued on the test material for 24 months. Body weights 

were slightly reduced in females received 12000 ppm when compared to the control. No effects 

were seen on survival, food consumption, clinical signs of toxicity, clinical laboratory findings, 

organ weight, or gross or histologic findings. For females, the LOEL was 12000 ppm based on 

slight decreases in mean body weight and the NOEL was 8000 ppm. For males, the LOEL was 

not established and the NOEL was 12000 ppm (the highest dose tested). This study was 

originally classified as supplementary (upgradeable) because a maximum tolerated dose (MTD) 

was not established for the carcinogenicity part of the study; in addition, there was a probability

of misdiagnosis of microscopic findings caused by tabulation of NAD (no abnormalities 

detected) for tissues in several animals with severe postmortem autolysis. 

Additional data (MRID# 42012901, 42012902) were submitted to the Agency in which 

adequately addressed the deficiencies described above. For chronic toxicity, the LOEL was 

estimated to be 12000 ppm (487 mg/kg/day for males and 757 mg/kg/day for females) based on 

slight decrease in body weight in females and an increase in acinar cell hyperplasia of the 

pancreas in males. The NOEL was 8000 ppm (385 mg/kg/day for males and 478 mg/kg/day for 

females). For carcinogenicity, the data indicate an increase in acinar cell hyperplasia of the 

pancreas in males at 12000 ppm (35%) when compared to controls (5.7%). In addition, there was 

an increase in the incidence of acinar cell adenoma of the pancreas in males in the 12000 ppm 

group (20%) when compared to the control (1.4%). 

The study was upgraded to acceptable and satisfies guideline requirement for a combined 

chronic toxicity/carcinogenicity study in rats (83-5).

870.4200b Carcinogenicity (feeding) - Mouse
Page 54 of 59

In a carcinogenicity study (MRID# 41063523), B6C3F1/Crl Br mice (60 sex/dose) were 

administered via diets with Quinclorac (97.4 or 98.3% a.i) at dose levels of 0, 250, 1000, 4000, 

or 8000 ppm (equivalent to 0, 37.5, 150, 600 or 1200 mg/kg/day) for 6 months or 78 weeks. Ten 

mice were terminated at 6 months. The remainders were continued on the test material for 18 

months. At the end of 13 weeks, body weights in males and females receiving 8000 ppm were 

significantly lower than controls by 9.6% and 7.4%, respectively. Body weights in males and 

females receiving 1000, 4000, and 8000 ppm for 78 weeks were significantly lower than controls 

(7.9 to 15.9% for males; 14.3 to 17.9 for females. Treatment-related body weight reductions 

compared to controls were also noted in satellite males and females receiving 4000 and 8000 

ppm for 6 months. Absolute liver weights were significantly reduced in male and female mice 

receiving 8000 ppm for 78 weeks, but there was no effect on liver-to-body weight ratio. 

Absolute kidney weights were decreased in males receiving 1000, 4000, and 8000 ppm and in 

females receiving 4000 and 8000 ppm for 78 weeks. Relative kidney weights were decreased in 

males receiving 1000, 4000, and 8000 ppm for 78 weeks. Dose-related increases in relative 

brain weights seen in males and females receiving 1000, 4000, and 8000 ppm. Absolute liver 

weights were also reduced in males receiving 4000 and 8000 ppm for 6 months, while absolute 

kidney weights were reduced in all treated males. A slight decrease in hematocrit values was 

noted in males and females receiving 8000 ppm for 6 months, but not 78 weeks. Effects on other 

hematological parameters were not of biological significance. There was no effect of dosing on 

mortality, food consumption, or clinical signs. The LOEL is 1000 ppm (150 mg/kg/day) based 

on effects on body weight. The NOEL is 250 ppm (37.5 mg/kg/day). A maximum tolerated dose 

(MTD) was approached based on decreased body weights in males and females receiving 8000 

ppm.

No evidence of histopathological or neoplastic lesions attributable to administration of any dose 

of Quinclorac was found in any tissue of any mouse.

This study is classified as Acceptable/Guideline and satisfies the guideline requirement for a 

carcinogenicity study (83-2) in mice.

A.4.6 Mutagenicity

Gene Mutation

870. 5100 

Bacterial reverse gene mutation

41063527

Acceptable/Guideline

Negative up to the limit dose (5000 μg/plate) with or without 

S9 in S. typhimurium strains TA98, TA100, TA1535, TA1537

870. 5100 

Bacterial reverse gene mutation

41063528

Acceptable/Guideline

Negative up to the limit dose (5000 μg/plate) with or without 

S9 in S. typhimurium strains TA98, TA100, TA1535, TA1537 

and E. coli strain WP2uvrA
Page 55 of 59

Cytogenetics

OPPTS 870.5385 

In vivo bone marrow cytogenic 

assay

MRID 41063530.

Acceptable/Guideline

Quinclorac was not clastogenic in this in vivo test. Negative 

in male and female NMRI mice at all doses up to limit dose 

(1000 mg/kg). Mid and high dose groups showed clinical 

signs of toxicity (irregular breathing, apathy, piloerection) but 

no toxicity to target cell was observed.

OPPTS 870.5395 

In vivo micronucleus assay in 

mice. MRID 41063529.

Acceptable/Guideline

Quinclorac did not induce clastogenic or aneugenic at any 

dose (500, 1000 or 2000 mg/kg) or sacrifice time. Toxic signs 

of irregular breathing, apathy, and piloerection were noted in 

the mid- and high-dose groups.

Other Genotoxicity

870.5300, In vitro mammalian 

forward gene mutation, CHO 

cells/HGPRT locus

MRID 41680503

Acceptable/guideline

Negative for gene mutations up to cytotoxic doses (2000 

μg/mL) with or without S9.

870.5300, In vitro mammalian 

chromosome aberration assay, 

human lymphocytes

MRID 41076103

Acceptable/guideline

Positive for chromosomal aberrations but only at cytotoxic 

concentrations (2000 μg/mL with S9 and 1000 μg/mL

without S9).

870.5550, Unscheduled DNA

synthesis in primary rat 

hepatocytes MRID 41063531

Acceptable/guideline

Negative up to cytotoxic dose (1520 μg/mL).

A.4.7 Neurotoxicity

870.6100 Delayed Neurotoxicity Study – Hen 

Not required.

870.6200 Acute Neurotoxicity Screening Battery -

Waived (HASPOC TXR 0056385)
Page 56 of 59

870.6200 Subchronic Neurotoxicity Screening Battery

Waived (HASPOC TXR 0056385)

870.6300 Developmental Neurotoxicity Study

HED HIARC did not recommend a DNT study. (TXR 0012902)

A.4.8 Metabolism

870.7485 Metabolism - Rat

The metabolism of quinclorac ([2,3,4-

14C)3,7—dichloro-8- quinolinecarboxylic acid) following 

oral administration was studied extensively in male and female CD rats (MRID 41063533). The 

compound was rapidly absorbed and eliminated in the urine following administration of single 

oral doses of [14C] quinclorac at 15 or 600 mg/kg and at 15 mg/kg after the animals were dosed 

with unlabeled quinclorac at 15 mg/kg/day for 14 days. Elimination in the urine 5 days after 

dosing accounted for 91 to 98% of the dose with only 1 to 4% eliminated in the feces. No 

radioactivity was detected in expired air. Biliary excretion was significant (11.5 to 14.5% of the 

dose) in animals receiving 600 mg/kg. However, most of this radioactivity was reabsorbed from 

the intestines and eliminated in the urine. Most of the radioactivity in the bile is associated with 

the glucuronide conjugate of quinclorac. The conjugate is apparently hydrolyzed in the intestines 

and reabsorbed. Almost all the radioactivity in the urine is unchanged quinclorac. Radioactive 

tissue residue levels 5 days after dosing were dose-dependent. Results from these and other 

(whole-body autoradiography and time-course) studies indicate that quinclorac may accumulate 

in the adrenal glands, bone marrow, thyroid, squamous epithelium of the non-fundic stomach, 

and ovaries. In 7-day time-course studies (oral gavage at 15 mg/kg/day or dietary at about 1,000 

mg/kg/day) maximum 14C residue levels were detected 30 minutes after the final dose; thereafter, 

residue levels decreased with time. Mean 14C residues in plasma were also detected at 30 

minutes in animals receiving single oral doses of 15, 100, or 600 mg/kg or 15 mg/kg/day for 7 

days. Elimination was biphasic with half-lives of 3 to 4 hours for the rapid phase at the low doses 

and a half-life of about 13 hours at 600 mg/kg. Peak plasma levels of radioactivity in animals 

receiving higher doses (1200 mg/kg or 600 mg/kg/day for 7 days) were noted for 7 to 48 hours 

postdosing: saturation kinetics were also noted at these higher doses. These studies are 

acceptable and fulfill EPA’s guidelines series 85-1.

870.7600 Dermal Absorption - Rat

Dermal absorption studies are not available.

A.4.9 Immunotoxicity

870.7800 Immunotoxicity

In an immunotoxicity study (MRID 48346101), Quinclorac (BAS 514 H, 99.9% a.i., Batch# 

479-480) was administered to female C57BL/6 J Rj mice (8/group) in the diet at dose levels of 0 
Page 57 of 59

(control), 500, 1500, or 5000 ppm (equivalent to 0, 176, 439, or 1760 mg/kg bw/day, 

respectively) for 28 consecutive days. Animals in the positive control group (8/group) received 

cyclophosphamide by gavage at a dose of 10 mg/kg/day throughout the study. Six days before 

necropsy, animals in all groups were immunized with a suspension of sheep red blood cells 

(4x108 SRBC/mL) by intravenous injection (0.5 mL/animal dose volume). All animals were 

evaluated for mortality, clinical signs, body weight changes, food consumption, and gross 

pathology. Immunotoxicity was assessed using an Enzyme-Linked Immunosorbent Assay

(ELISA) approach that measured the concentration of serum anti-SRBC immunoglobulin M 

(IgM). The absolute and relative (to terminal body weight) organ weights of the spleen and 

thymus were determined at necropsy.

There were no treatment related effects on mortality, clinical signs, body weight changes, food 

consumption, organ weights, or gross pathology at any dose concentration that were considered 

treatment related. 

The systemic toxicity NOAEL is 5000 ppm (equivalent to 1760 mg/kg bw/day); the LOAEL was 

not established, tested above the limit dose.

For immunotoxicity, there were no treatment-related effects on serum anti-SRBC IgM antibody 

levels as measured by an ELISA, or thymus and spleen weights at any diet concentration. High 

inter-individual variability was seen in the treatment and vehicle control groups. Examination of 

individual animal data did not show any trend or distribution that would demonstrate significant 

suppression of the anti-SRBC IgM response. The mean IgM result from positive control group 

was 79.6% lower than the vehicle control group, showing it was valid for evaluating immunosuppression. The positive control group confirmed the ability of the test system to detect 

immuno-suppressive effects and confirmed the validity of the study design.

A Natural Killer (NK) cell activity assay was not performed in this study. The toxicology 

database for quinclorac does not reveal any evidence of treatment-related effects on the immune 

system. The overall weight of evidence suggests that this chemical does not directly target the 

immune system. Under HED guidance, a NK cell activity assay is not required at this time.

Under conditions of this study, the immunotoxicity NOAEL is 5000 ppm (equivalent to 1760 

mg/kg/day, the highest dose tested and above the limit dose); the LOAEL was not established.

This immunotoxicity study is classified as acceptable/guideline and satisfies the guideline 

requirement for an immunotoxicity study (OPPTS 870. 7800) in rodents.

A.4.9 Special/Other Studies (optional section)

None.
Page 58 of 59

Appendix B. Review of Human Research

This risk assessment relies in part on data from studies in which adult human subjects were 

intentionally exposed to a pesticide or other chemical. These data, which include studies from 

the Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1); the Agricultural Handler 

Exposure Task Force (AHETF) database; the Outdoor Residential Exposure Task Force 

(ORETF) database; and the Agricultural Re-entry Task Force (ARTF) database are subject to 

ethics review pursuant to 40 CFR 26, have received that review, and are compliant with 

applicable ethics requirements. For certain studies that review may have included review by the 

Human Studies Review Board. Descriptions of data sources as well as guidance on their use can 

be found at http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

http://www.epa.gov/pesticides/science/post-app-exposure-data.html.
Page 59 of 59

Appendix C: International Residue Limits 

Quinclorac (PC Code 128974; Date of Request 3/14/2013)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada-proposed* Mexico1 Codex

40 CFR 180.463 - proposed

Plant/Livestock: quinclorac, 3,7-dichloro8-quinolinecarboxylic acid + methyl ester

3,7-dichloro-8-

quinolinecarboxylic 

acid + methyl ester

None

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

US Canada Mexico1 Codex

Rapeseed subgroup 20A 1.5 1.5

Completed by: M. Negussie; 3/14/2013

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

* Canadian MRLs are being established concurrently