Quizalofop-P-ethyl Human Health Risk Assessment DP No. 384660 and 386678

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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF

CHEMICAL SAFETY AND

POLLUTION PREVENTION

MEMORANDUM

Date: November 17, 2011

SUBJECT: Quizalofop-P-ethyl: Human Health Risk Assessment for New Uses on Sorghum, 

Rapeseed Crop Group 20 A, and Field Corn

PC Code: 128709 DP Barcode: D384660 and D386678

Decision No.: 441518 and 443799 Registration No.: 352-541 and 352-542

Petition No.: 0E7802 and 1F7822 Regulatory Action: Tolerance Petition

Risk Assessment Type: Single Chemical / Aggregate Case No.: NA

TXR No.: NA CAS No.: 100646-51-3

MRID No.: 48273601, 48260704 and 48310101 40 CFR: § 180.441

FROM: Ideliz Negrón-Encarnación, Ph.D., Risk Assessor

Seyed Tadayon, Chemist

John Doherty, Ph.D., Toxicologist

Risk Assessment Branch V

Health Effects Division (7509P)

Office of Pesticide Programs

THROUGH: William Donovan, Ph.D., Chemist

Michael Metzger, Branch Chief

Risk Assessment Branch V

Health Effects Division (7509P)

Office of Pesticide Programs

TO: Laura Nollen, Risk Manager

Risk Management Division (RM 5; 7508 P)

and

Mindy Ondish, Risk Manager 

Risk Management Division (RM 25; 7508P)
Quizalofop-P-ethyl Human Health Risk Assessment DP No. 384660 and 386678

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Table of Contents

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

2.0 HED Recommendations....................................................................................................... 6

2.1 Data Deficiencies/Conditions of Registration.................................................................. 6

2.2 Tolerance Considerations................................................................................................. 6

2.2.1 Enforcement Analytical Method .................................................................................. 7

2.2.2 International Harmonization......................................................................................... 7

2.2.3 Recommended Tolerances............................................................................................ 7

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

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

3.1 Chemical Identity ........................................................................................................... 11

3.2 Physical/Chemical Characteristics................................................................................. 11

3.3 Pesticide Use Pattern...................................................................................................... 12

3.4 Anticipated Exposure Pathways..................................................................................... 14

3.5 Consideration of Environmental Justice ........................................................................ 14

4.0 Hazard Characterization and Dose-Response Assessment................................................ 15

4.1 Toxicology Studies Available for Analysis ................................................................... 15

4.2 Absorption, Distribution, Metabolism, & Elimination (ADME)................................... 15

4.2.1 Dermal Absorption ..................................................................................................... 15

4.3 Toxicological Effects ..................................................................................................... 15

4.4 Safety factor for Infants and Children (FQPA Safety Factor) ....................................... 16

4.4.1 Completeness of the Toxicology Database ................................................................ 16

4.4.2 Evidence of Neurotoxicity.......................................................................................... 16

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal............. 16

4.4.4 Residual Uncertainty in the Exposure Database......................................................... 19

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

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

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

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

Assessment................................................................................................................................ 22

5.0 Dietary Exposure and Risk Assessment ............................................................................ 23

5.1 Metabolite/Degradate Residue Profile ........................................................................... 23

5.1.1 Summary of Plant and Animal Metabolism Studies .................................................. 23

5.1.3 Residues of Concern Summary and Rationale ........................................................... 23

5.2 Food Residue Profile...................................................................................................... 24

5.3 Water Residue Profile .................................................................................................... 27

5.4 Dietary Risk Assessment................................................................................................ 27

5.4.1 Description of Residue Data Used in Dietary Assessment......................................... 27

5.4.2 Percent Crop Treated Used in Dietary Assessment.................................................... 28

5.4.3 Acute Dietary Risk Assessment ................................................................................. 28

5.4.4 Chronic Dietary Risk Assessment .............................................................................. 28

5.4.5 Cancer Dietary Risk Assessment................................................................................ 28

5.4.6 Summary Table........................................................................................................... 28

6.0 Residential (Non-Occupational) Exposure/Risk Characterization .................................... 29

6.5 Spray Drift...................................................................................................................... 29
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7.0 Aggregate Exposure/Risk Characterization....................................................................... 29

8.0 Cumulative Exposure/Risk Characterization..................................................................... 29

9.0 Occupational Exposure/Risk Characterization .................................................................. 30

10.0 References.......................................................................................................................... 31

Appendix A. Toxicology Profile and Executive Summaries....................................................... 31

Appendix A. Toxicology Profile and Executive Summaries....................................................... 32

A.1 Toxicology Data Requirements...................................................................................... 32

A.2 Toxicity Profiles............................................................................................................. 33
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1.0 Executive Summary

BACKGROUND: Quizalofop ethyl is a selective herbicide used for the control of annual and 

perennial grasses in crop- and non-croplands. Presently, quizalofop ethyl is registered for uses 

on canola, crambe, cotton, dry beans, dry and succulent peas, lentils, mint, snap beans, soybean, 

sugar beets, barley, flaxseed, sunflower and wheat. This document addresses petitions from 

DuPont and Interregional Research Project No. 4 (IR-4) for the registration of Assure ® II

Herbicide (EPA Reg. No. 352-541) Herbicide, (0.88 lb ai /gal emulsifiable concentrate) for use 

on sorghum, rapeseed crop group 20 A (except flaxseed), and corn. The Assure ®Herbicide 

product formulation contains 10.3% quizalofop-P-ethyl as the sole active ingredient, which is the 

R-enantiomer, while the previously registered quizalofop ethyl is a 50-50 racemic mixture of Rand S-enantiomers. HED has determined that the toxicological profiles of the racemic mixture 

and that of R-enantiomer are sufficiently similar, and the available data on the former are 

adequate to support registration of products containing the enriched R-enantiomer.

Tolerances are established under 40 CFR §180.441(a)(1) for the combined residues of quizalofop 

ethyl and quizalofop, all expressed as quizalofop ethyl in/on agricultural commodities except as 

listed in Section (a)(3), under §180.441(a)(2) for the combined residues of quizalofop ethyl, 

quizalofop, and quizalofop methyl, all expressed as quizalofop ethyl, for egg, fat, meat, meat 

byproducts, milk and milk fat, and under §180.441(a)(3) for the combined residues of 

quizalofop-P-ethyl ester, quizalofop-P acid, and the S-enantiomers of the ester and the acid, 

expressed as quizalofop-P-ethyl ester, for sugar beet, canola, cotton, lentil, peppermint and 

spearmint. Under PP# 0E7802, IR-4 is proposing to amend quizalofop ethyl tolerance 

expressions under 40 CFR part 180.441.

E.I. du Pont de Nemours & Company (Dupont) is proposing to amend the label of Assure® II 

herbicide to include uses on herbicide-tolerant field corn containing the aryloxyalkanoate 

dioxygenase-1 gene (DAS-40278-9) and in propagation of corn seed containing DAS-40278-9. 

The proposed uses are postemergence applications to field and seed corn containing the 

quizalofop-resistant trait at a maximum seasonal rate of 0.083 lb ai/A. The proposed preharvest 

interval (PHI) is 30 days for forage; a PHI for corn grain or stover is not specified. 

The IR-4 is proposing to amend the label of Assure® II herbicide to include uses on sorghum 

grain containing the DuPontTM INZENTM AII Herbicide Tolerance Trait and on rapeseed 

subgroup 20A, except flaxseed. The proposed uses are postemergence applications to sorghum 

at a maximum seasonal rate of 0.138 lb ai/A, and postemergence applications to rapeseed 

subgroup 20A at a maximum seasonal rate of 0.124 lb ai/A. The proposed preharvest intervals 

(PHIs) are 30 days for sorghum forage, 45 days for sorghum grain and stover, and 60 days for 

rapeseed subgroup 20A.

HAZARD ASSESSMENT: Quizalofop ethyl has low acute toxicities via the oral, dermal, and 

inhalation routes. It is not an eye or dermal irritant nor a skin sensitizer. Following oral 

administration, quizalofop ethyl is rapidly absorbed and excreted via urine and feces. Liver is 

the target organ as evidenced by increased liver weight and histopathological changes in the 

liver.
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There were no effects observed in oral toxicity studies that could be attributable to a single-dose 

exposure. Hence, a dose and endpoint have not been selected for assessment of acute exposure. 

Similarly, there was no observed toxicity in a dermal subchronic study at the highest dose tested 

(above the limit dose) so no dermal risk assessment is needed. Inhalation toxicity studies for 

occupational exposure assessment are waived based on the low exposure expected by the current 

and proposed use patterns. A chronic reference dose (cRfD) was established based on a 

combined chronic toxicity/carcinogenicity study in rats. Mutagenicity studies conducted on 

quizalofop ethyl did not demonstrate evidence of mutagenic potential. The Cancer Peer Review 

Committee determined that quizalofop ethyl should be classified as Category D (not classifiable 

as to human carcinogenicity). As such, a cancer risk assessment was not conducted.

Developmental studies in rats and rabbits and a two-generation reproduction study in rats 

showed no evidence (qualitative or quantitative) for increased susceptibility following in utero

and/or pre/post-natal exposure to quizalofop ethyl. The toxicity database is adequate in terms of 

endpoint and dose response information to characterize the potential for prenatal or postnatal risk 

to infants and children. Based on the above data, the 10x Food Quality Protection Act Safety 

Factor (FQPA SF) to account for enhanced sensitivity of infants and children has been reduced 

to 1x. HED has confidence that the risk assessment conducted with no additional safety factor 

will provide a reasonable certainty of no harm to the safety of infants and children.

The available toxicology data are sufficient to assess the critical exposure scenarios and for 

endpoint and dose-response evaluation. Due to the adequacy of data, the combined uncertainty 

factor (UF) of 100x was used for the risk assessment (10x for intraspecies variation and 10x for 

interspecies extrapolation). Since there is no additional UF, margin of exposure (MOE) greater 

than 100 are considered to represent risks below HED’s level of concern (LOC). 

OCCUPATIONAL RISK: A separate memo was issued to address the occupational risk of 

quizalofop ethyl to pesticide handlers and post-application workers. As noted above, no doses or 

endpoints for dermal or inhalation exposure were selected or needed. Therefore, a quantitative 

estimate of occupational risk was not determined. The acute toxicity categories are IV for both 

routes of exposure, and a 12-hour re-entry interval (REI) was established under the worker 

protection standard (WPS).

RESIDENTIAL RISK: Quizalofop ethyl has no registered homeowner or ornamental uses and none 

are being proposed.

DIETARY RISK: An acute dietary risk assessment was not performed, as an acute endpoint was 

not identified in the hazard assessment. Similarly no cancer risk assessment was needed, as 

quizalofop ethyl was not classifiable with regard to carcinogenicity.

A chronic dietary exposure assessment was conducted using the Dietary Exposure Evaluation 

Model - Food Consumption Intake Database (DEEM-FCID, ver.2.03). The inputs used were 

(i) tolerance level residues for all commodities, (ii) 100 percent crop treated (%CT), (iii) 

DEEMTM ver. 7.78) default processing factors, and (iv) drinking water numbers generated by 

Pesticide Root Zone Model-Exposure Analysis and Modeling System (PRZM-EXAMS) using 

the maximum application rate per season for quizalofop ethyl on dry peas in Michigan. Under 
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this scenario, children (1-2 years) were found to have the maximum chronic dietary risk at 29% 

of the chronic population adjusted dose (cPAD). This is well below HED’s level of concern of 

100% of cPAD.

AGGREGATE RISK: Aggregate risk estimates take into account dietary and non-dietary

residential sources of exposure. As there are no registered or proposed uses of quizalofop that 

would result in non-dietary residential exposure, the aggregate risk estimates are equivalent to 

the chronic dietary risk estimates discussed above and are below HED’s level of concern. 

In summary, this risk assessment indicates that adding field corn, sorghum and the rapeseed 

subgroup 20A, to the existing uses of quizalofop-P-ethyl, will not pose a health risk to humans.

2.0 HED Recommendations

HED can recommend the registration and tolerance for the use of quizalofop-P-ethyl on field 

corn, sorghum and the rapeseed subgroup 20A. Additional data needs are outlined in section 2.1 

below. The specific tolerance recommendations are discussed in 2.2, and label modifications are 

discussed in section 2.3

2.1 Data Deficiencies/Conditions of Registration

HED has examined the residue chemistry database for quizalofop ethyl. Pending submission of 

the items requested in the residue chemistry chapter (D395630, I. Negron, 15Nov2011), there are

no residue chemistry issues that would preclude granting a registration for the proposed uses on 

corn, sorghum and rapeseed, subgroup 20A (except flaxseed) and the establishment of the 

corresponding tolerances. In addition to the items described below, HED expects to receive the 

report on the storage stability of the field corn samples and it corresponding processed 

commodities.

2.2 Tolerance Considerations

• The proposed tolerance level for corn forage and grain is 0.01 ppm. However, by

using the OECD calculator the appropriate tolerance level for corn forage and 

grain is 0.02 ppm. A revised tolerance should be proposed.

• The petitioner proposed separate tolerances in/on the individual commodities of 

the rapeseed subgroup 20A, except flaxseed [borage seed, crambe seed, gold of 

pleasure seed, cuphea seed, echium seed, hare’s ear mustard seed, lesquerella 

seed, lunaria seed, meadowfoam seed, milkweed seed, mustard seed, oil radish 

seed, poppy seed, rapeseed, sesame seed, and sweet rocket seed] at 1.0 ppm. The 

recommended tolerance differs since the residues levels were scaled to reflect the 
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proposed use pattern and a tolerance was estimated by using the OECD 

calculator. Therefore, for the proposed use pattern a subgroup tolerance in/on 

rapeseed subgroup 20A, except flaxseed should be proposed at 1.5 ppm. Also, a 

tolerance of 2.0 ppm is recommended for rapeseed, subgroup 20A, meal, except 

flaxseed.

• The proposed tolerance level for sorghum stover is 0.35 ppm. However, by using 

the OECD calculator the appropriate tolerance level for sorghum stover is 0.3 

ppm. A revised tolerance should be proposed. 

• The proposed tolerances should be revised to reflect the correct commodity 

definitions as specified in the residue chemistry chapter.

2.2.1 Enforcement Analytical Method

860.1340 Residue Analytical Methods

• After reviewing Morse Method Meth-147 against the Tolerance Method 

Validation (TMV) Review Checklist, provided the solvent exchange modification 

made by the ILV laboratory is incorporated into the final method, the analytical 

method data satisfy the requirements. A TMV by ACB will not be necessary.

2.2.2 International Harmonization

No Codex MRLs have been established for residues of quizalofop ethyl. Canadian MRLs have 

been established for residues of quizalofop ethyl and quizalofop in/on oriental mustard seeds 

(condiment type and oil seed type), and rapeseeds (canola), the only crops included in the subject 

petition, at 0.05 ppm. The US tolerance can not be harmonized with the Canadian MRL for the

commodities of the Rapeseed, subgroup 20A. No Mexican MRLs have been established for any 

of the requested crops. 

2.2.3 Recommended Tolerances

Field Corn, Sorghum and Rapeseed Subgroup 20A (except flaxseed)

The OECD MRL calculator (March 2011 version) was utilized for determining appropriate 

tolerance levels for RACs. An adequate number of field trials at ~1x the proposed use rate are 

available to recommend tolerances for corn (forage, grain, and stover) and sorghum (forage, 

grain, stover and aspirated grain fractions). Individual tolerances for each member of the 

Rapeseed Subgroup 20A are no longer required. Canola seed is the representative commodity of 

crop subgroup 20A for which a tolerance is established in the 40 CFR §180.441(a)(3). Pending 

revision of 40 CFR §180.441(a)(3), separate tolerances for canola seed and canola meal should
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be removed. New tolerances were determined for the rapeseed subgroup 20A and the meal 

processed commodity by adjusting for differences between the proposed and study application 

rates. These new tolerances should be included in the revised 40 CFR § 180.441 (a)(1).

HED recommends the amendment of the tolerances in 40 CFR part 180.441 by combining the 

tables for sections (a)(1) and (a)(3) into one table under section (a)(1), and by removing section 

(a)(3). Also, the tolerance expressions under section (a)(1), (a)(2) and (c) can be modified as 

follows: 

Section (a)(1): “Tolerances are established for residues of the herbicide quizalofop ethyl, 

including its metabolites and degradates, in or on the commodities in the table below. 

Compliance with the tolerance levels specified below is to be determined by measuring only

those quizalofop ethyl residues convertible to 2-methoxy-6-chloroquinoxaline, expressed as the 

stoichiometric equivalent of quizalofop ethyl, in or on the commodity.” 

Section (a)(2): “Tolerances are established for residues of the herbicide quizalofop ethyl, 

including its metabolites and degradates, in or on the commodities in the table below. 

Compliance with the tolerance levels specified below is to be determined by measuring only

those quizalofop ethyl residues convertible to quizalofop (2-[4-(6-chloroquinoxalin-2-yloxy)phenoxy]propanoic acid), expressed as quizalofop, in or on the commodity.”

Section (c): “Tolerances with regional registrations. Tolerances with regional registration are 

established for residues of the herbicide quizalofop ethyl, including its metabolites and 

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

specified below is to be determined by measuring only those quizalofop ethyl residues 

convertible to 2-methoxy-6-chloroquinoxaline, expressed as the stoichiometric equivalent of 

quizalofop ethyl, in or on the commodity.”

The petitioner should submit a revised section F reflecting the recommended tolerances and 

commodity definitions presented in Table 2.2.3. These new tolerances should be included in the 

revised 40 CFR § 180.441 (a)(1).
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Table 2.2.3. Tolerance Summary for Quizalofop-P-ethyl

Commodity Established/Proposed 

Tolerance (ppm)

Recommended 

Tolerance (ppm)

Comments

Correct Commodity Definition

Corn, forage 0.01 0.02 Corn, field, forage

Corn, grain 0.01 0.02 Corn, field, grain

Corn, stover 0.03 0.03 Corn, field, stover

Canola, seed11.0 Remove

Gold of Pleasure, seed 1.0 Not needed

Borage, seed 1.0 Not needed

Crambe, seed 1.0 Not needed

Cuphea, seed 1.0 Not needed

Echiuim, seed 1.0 Not needed

Hare’s ear mustard, seed 1.0 Not needed

Lesquerella, seed 1.0 Not needed

Lunaria, seed 1.0 Not needed

Meadowfoam, seed 1.0 Not needed

Milkweed, seed 1.0 Not needed

Mustard, seed 1.0 Not needed

Oil Radish, seed 1.0 Not needed

Poppy, seed 1.0 Not needed

Rapeseed 1.0 Not needed

Sesame, seed 1.0 Not needed

Sweet Rocket, seed 1.0 Not needed

Canola, meal1,21.5 Remove

Rapeseed subgroup 20A, 

meal, except flaxseed2

-- 2.0

Gold of Pleasure, meal 1.5 Not needed

Crambe, meal 1.5 Not needed

Rapeseed, subgroup 20A, 

except flaxseed3

-- 1.5

Sorghum, grain 0.2 0.20 Sorghum, grain, grain

Sorghum, forage 0.2 0.20 Sorghum, grain, forage

Sorghum, stover 0.35 0.30 Sorghum, grain, stover

Sorghum, aspirated grain 1.0 1.0 Sorghum, grain, aspirated grain 

fractions

1 Established under 40 CFR §180.441(a)(3).

2 The available canola processing data was translated to the rapeseed subgroup 20A to calculate and propose a 

tolerance for rapeseed, subgroup 20A, meal.

3 Canola seed is a member of crop subgroup 20A. Pending revision of 40 CFR §180.441(a)(3), the established

separate tolerances for canola seed and canola meal may be removed.
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2.3 Label Recommendations

860.1200 Directions for Use

The following changes are recommended in the draft label of Assure® II herbicide: 

• The application rate on the supplemental label for field corn and sorghum is 

presented in terms of “oz product/A.” The label should be amended to read “fl. 

oz product/A”.

• The proposed grazing restrictions are impractical for field corn and sorghum and 

should be removed from the product label.

• The supplemental label for field corn should specify the PHI for corn grain and 

stover, and the concentration of either crop oil concentrate or nonionic surfactant. 

These parameters should reflect those used in the crop field trials.

3.0 Introduction

Dupont has submitted a label amendment for Assure® II herbicide (EPA Reg. No. 352-541) to 

include uses on corn seed containing DAS-40278-9 and field corn containing DAS-40278-9. 

The Interregional Research Project No. 4 (IR-4) is proposing to amend the label of Assure® II 

herbicide to include uses on sorghum grain containing the DuPontTM INZENTM AII Herbicide 

Tolerance Trait and on rapeseed subgroup 20A, except flaxseed [borage, crambe, gold of 

pleasure (Camelina), cuphea, echium, hare’s ear mustard, lesquerella, lunaria, meadowfoam, 

milkweed, mustard seed, oil radish, poppy seed, rapeseed (canola), sesame, and sweet rocket]. 

Assure®herbicide contains quizalofop-P-ethyl as the sole ai, which is an R-enantiomer of 

quizalofop ethyl. Chemically, quizalofop ethyl is a racemic mixture containing R- and Senantiomers and the former is the pesticide active component. Quizalofop ethyl is a selective 

preplant, pre- and postemergence herbicide registered for the control of annual and perennial 

grasses on noncrop and on crop land areas.

The chemical structure of quizalofop-P-ethyl is presented in Table 3.1 and its physicochemical 

properties are presented in Table3.2.
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3.1 Chemical Identity

Table 3.1 Test Compound Nomenclature

Chemical structure

N

Cl N

O

O

CH3

O

O

CH3

Common name Quizalofop-P-ethyl

Company experimental name Not provided

IUPAC name ethyl (R)-2-[4-((6-chloroquinoxalin-2-yl)oxy)phenoxy]propanoate

CAS name (2R)-2-[4-[(6-chloro-2-quinoxalinyl)oxy]phenoxy]propanoic acid, ethyl ester

CAS registry number 100646-51-3

End-use product (EP) 0.88 lb ai /gal EC formulation (EPA Reg. No. 352-541)

3.2 Physical/Chemical Characteristics

TABLE 3.2 Physicochemical Properties of the Technical Grade Test Compound Quizalofop-P-Ethyl.

Parameter Value Reference

Melting point 76.0-77.0 C (pure form) CB Nos. 5852 & 5853, 

3/29/90, W. Hazel pH 6.6 (1% aqueous slurry)

Density 1.35 g/cm3

at 20 C (pure form)

Water solubility 0.4 ppm (20 C)

Solvent solubility

acetone

benzene

carbon disulfide

chloroform

cyclohexanone

dichloromethane

dimethyl sulfoxide

ethanol

n-hexane

methanol

tetrahydrofuran

toluene

xylene

g/L at 20 oC

650

680

660

1350

440

1970

200

22

5

22

1160

430

360

Vapor pressure 8.3 x 10-10 mm Hg (20 C)

Dissociation constant, pKa Not applicable

Octanol/water partition coefficient log POW = 4.66

UV/visible absorption spectrum Not available
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3.3 Pesticide Use Pattern

The petitioner has submitted a Section B along with draft specimen supplemental labeling for the 

0.88 lb ai/gal EC formulation of quizalofop-P-ethyl (Assure® II Herbicide; EPA Reg. No. 352-

541). IR-4 is proposing a label amendment for this product to add new uses on sorghum grain 

containing the DuPontTM INZENTM AII Herbicide Tolerance Trait and rapeseed subgroup 20A, 

except flaxseed. The currently registered EPA label, dated 4/14/2010, was obtained from PPLS. 

The currently registered uses include canola, crambe, cotton, crops grown for seed, eucalyptus, 

dry beans (including Chickpea), dry and succulent peas, flaxseed, hybrid poplar plantings, 

lentils, mint (spearmint and peppermint), pineapple, ryegrass grown for seed, snap beans, 

soybeans, sugar beets, sunflowers, and noncrop areas. DuPont Crop Protection is also requesting

the addition of genetically modified field corn (containing DAS-40278-9) to the label of Assure® 

II Herbicide; EPA Reg. No. 352-541. The use patterns for the proposed new uses are presented 

in Table 3.3.
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Table 3.3 Summary of Directions for Use of Quizalofop-P-ethyl Formulation.1

Applic. Timing, 

Type, and Equip.

Form.

[EPA Reg. 

No.]

Applic. 

Rate 

(lb ai/A)

Max. No. 

Applic. 

per 

Season

Max. 

Seasonal 

Applic. Rate

(lb ai/A)

RTI 

(days)

PHI 

(days)

Use Directions and 

Limitations

Field Corn containing DAS-40278-9

Postemergence, 

Broadcast foliar

application by 

ground

0.88 lb ai 

/gal EC

[352-541]

0.034-

0.083 2 0.083 NS2 30 (forage)3

For use in propagation of 

corn seed containing DAS40278-9 and quizalofoptolerant field corn 

containing DAS-40278-9. 

Applications may be made 

to emerged corn that is at 

the V2 through V6 stage of 

development. 

Applications must include 

either a crop oil 

concentrate or a non-ionic 

surfactant. Aerial 

application is prohibited. 

The grazing of livestock 

on treated corn or 

harvesting forage within 

30 days of application is 

prohibited.

Sorghum, grain containing the DuPontTM INZENTM AII Herbicide Tolerance Trait

Postemergence, 

Broadcast 

application by 

ground or air

0.88 lb ai 

/gal EC

[352-541]

0.034-

0.083 2 0.138 NS2

30 

(forage)4

45 (grain 

and 

stover)

Applications must include 

either a crop oil 

concentrate or a non-ionic 

surfactant.

Rapeseed Subgroup 20A, Except Flaxseed, Seed

[includes Borage, Crambe, Cuphea, Echium, Gold of Pleasure (Camelina), Hare’s ear mustard, Lesquerella, 

Lunaria, Meadowfoam, Milkweed, Mustard seed, Oil Radish, Poppy seed, Rapeseed (Canola), Sesame, and 

Sweet Rocket]

Postemergence, 

Broadcast 

application by 

ground or air

0.88 lb ai 

/gal EC

[352-541]

NS NS 0.124 7 60

Applications must include 

either a crop oil 

concentrate or a non-ionic 

surfactant.

1 General use directions, restrictions, and precautions were obtained from the currently registered label for Assure® 

II Herbicide (EPA Reg. No. 352-541), dated April 14, 2010

2 NS = Not specified

3 The supplemental labeling indicates that a 30-day PHI is proposed for forage; a PHI for corn grain or stover is not 

specified. The currently registered label indicates that the grazing of livestock in treated areas or feeding of forage, 

hay, or straw from the treated crops to livestock is prohibited. 

4 The Section 3 label describes the crop rotation restrictions as required.
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3.4 Anticipated Exposure Pathways

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

proposed new use of quizalofop-P-ethyl on sorghum, rapeseed subgroup 20 A, and field corn.

Humans may be exposed to quizalofop-P-ethyl in food and drinking water, since quizalofop-Pethyl may be applied directly to growing crops and application may result in quizalofop-P-ethyl

reaching surface and ground water sources of drinking water. There are no residential uses of 

quizalofop-P-ethyl, so there is not likely to be exposure in residential or non-occupational 

settings. In an occupational setting, applicators may be exposed while handling the pesticide 

prior to application, as well as during application. There is a potential for post-application 

exposure for workers re-entering treated fields. 

Risk assessments have been previously prepared for the existing uses of quizalofop-P-ethyl. 

This risk assessment considers all of the aforementioned exposure pathways based on the 

proposed new uses of quizalofop-P-ethyl, 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 postapplication are evaluated. 

Further considerations are currently in development as OPP has committed resources 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.
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4.0 Hazard Characterization and Dose-Response Assessment

This section was adapted from Quizalofop-P-ethyl: Human Health Risk Assessment for New 

Uses on Barley, Flaxseed, Sunflower and Wheat., prepared by S. Oonnithan, dated August 10, 

2006 for D310869. The series 870.7800 immunotoxicity screen study was the only new toxicity

study submitted and reviewed since 2006.

4.1 Toxicology Studies Available for Analysis

Studies Considered: 

• Developmental studies in rats and rabbits. 

• Subchronic - 28-day dermal study in rats, 90-day oral toxicity in rats and dogs. 

• Chronic toxicity studies in dogs and rats, carcinogenicity studies in rats and mice. 

Repro/Developmental - 2-generation reproduction study in rats and developmental 

studies in rats and rabbits. 

• Other - Mutagenicity screens, Immunotoxicity screening

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

Metabolism study in rats showed that following oral administration, quizalofop ethyl is readily 

absorbed from the gastrointestinal tract and is excreted rapidly via urine and feces. The major 

metabolite of quizalofop ethyl is the corresponding acid, which is metabolized further. 

According to W. Phang, the metabolism study has several deficiencies and the study is classified 

as SUPPLEMENTARY (TXR # 006487, 12/3/87). 

4.2.1 Dermal Absorption

The results of a dermal absorption study in rats (MRID 00146679) indicated that with a10-hour 

exposure at doses of 0.19, 1.9, or 19 mg/rat, the percent of absorption was 8.38, 3.27, and 2.9% 

of the applied dose, respectively. A dermal absorption factor is not applicable since dermal risk 

assessments are not required. 

4.3 Toxicological Effects

Liver is the target organ as evidenced by increased liver weight and histopathological changes in 

the liver. Developmental studies in rats and rabbits and a two-generation reproduction study in 

rats showed no evidence (qualitative or quantitative) for increased susceptibility following in 

utero and/or pre/post-natal exposure to quizalofop ethyl. Quizalofop ethyl does not appear to be a 

neurotoxic chemical since no treatment-related effects on brain weight or histopathology of the 

nervous system were observed in studies that measure these endpoints. The Cancer Peer Review 

Committee determined that quizalofop ethyl should be classified as Category D (not classifiable 
Quizalofop-P-ethyl Human Health Risk Assessment DP No. 384660 and 386678

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as to human carcinogenicity). Mutagenicity studies conducted on quizalofop ethyl did not 

demonstrate evidence of mutagenic potential. 

4.4 Safety factor for Infants and Children (FQPA Safety Factor)

The database is adequate in terms of endpoint and dose-response information to characterize the 

potential for pre- or post-natal exposure to infants and children. There is no evidence of 

increased susceptibility following in utero exposure in rat or rabbit developmental toxicity

studies and pre-/post-natal exposure in a two-generation reproduction study in rats. There are no 

concerns and no residual uncertainties for pre- and postnatal toxicity. Quizalofop ethyl does not 

appear to be a neurotoxic chemical based on a weight-of-evidence consideration. Based on the 

available data, the 10x FQPA SF to account for enhanced sensitivity of infants and children (as 

required by FQPA) was reduced to 1x. The HED has confidence that the risk assessment 

conducted with no additional safety factor will provide a reasonable certainty of no harm to the 

safety of infants and children. 

4.4.1 Completeness of the Toxicology Database

Adequacy of the Toxicity Database: The toxicology database for quizalofop ethyl is adequate for 

FQPA consideration. The following studies are available: 

- Developmental toxicity studies in rats and rabbits (acceptable). 

- Two generation reproduction study in rats (acceptable). 

4.4.2 Evidence of Neurotoxicity

Although no neurotoxicity studies were available, the HED determined that quizalofop ethyl does 

not appear to be a neurotoxic chemical. There were no treatment-related effects on brain weight 

or histopathology of the nervous system seen in studies that measured these endpoints. There 

was no evidence of effects on functional development observed in a postnatal segment of the 

reproduction study in rats. 

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal

Developmental Toxicity: In a developmental toxicity study , Quizalofop ethyl technical 

(99.1%, ai) was administered to pregnant JCL:SD rats (20-24/dose) by gavage in 2 mL/kg of 

0.5% carboxymethylcellulose at dose levels of 0, 30, 100, or 300 mg/kg bw/day from gestation days 

6 through 15. The study was conducted in two segments; one segment in which rats were 

sacrificed on GD 21, and the other in which rats were allowed to deliver. The nursing 

subgroups were maintained for three additional weeks. 
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For maternal toxicity, there were no deaths, abortions, or clinical signs observed in treated and 

control rats. Decreased body weight gains and food consumption were observed in 100- and 300-

mg/kg/day treated rats. Increased liver weights were observed in 300 mg/kg/day treated rats. 

Decreased average number of corpora lutea per litter was observed at 100 mg/kg/day and increased 

rate of implantation was observed at 100 and 300 mg/kg/day. Under the conditions of the study, 

the maternal LOAEL is 100 mg/kg bw/day, based on decreased body weight gains and food 

consumption. The maternal NOAEL is 30 mg/kg bw/day. 

For developmental toxicity, statistically significant increase of skeletal variations (mostly fourteenthrib variety) was observed in fetuses in the 300 mg/kg/day group. The biological significance of the 

increase in the number of ribs in these fetuses was questionable since the skeletal examination 

of the nursing groups revealed no abnormality in the frequency of appearance of 14th-rib 

variety among the 8-week old. Apparently, these 14th-ribs might have fused with the vertebral 

arches and disappeared in the course of postnatal growth. No significant abnormality was seen 

in the visceral examination. The developmental toxicity study in the rat is classified 

acceptable/guideline and satisfies the guideline requirement (OPPTS 870.3700; OECD 414). 

In another developmental toxicity study , quizalofop ethyl technical (99.1%, a.i.) was administered to 

pregnant NSW rabbits (16/dose) by gavage at dose levels of 0, 7, 20, or 60 mg/kg bw/day from 

gestation days 7 through 19. On GD 29, fetuses were delivered with cesarean section from the 

surviving females prior to sacrifice. Decreased body weight gains and food consumption were 

observed in the 60 mg/kg group during the dosing period (gestation days 7-20). During the posttreatment period (GDs 20-29), the mean body weight gain was significantly elevated compared 

to the control. No other significant treatment-related effects were reported. In the range-finding 

study, decreased body weight gains and food consumption was observed in the 75 mg/kg group. 

Increased incidence of abortion was observed in 60 and 75 mg/kg groups compared to the 

control. Under conditions of the study, the maternal LOAEL is 60 mg/kg bw/day, based on 

decreased body weight gains and food consumption. The maternal NOAEL is 20 mg/kg bw/day. 

No evidence of developmental toxicity was observed in the range-finding and the final 

developmental toxicity studies. The developmental NOAEL is 60 mg/kg bw/day (HDT). The 

developmental toxicity study in the rabbit is classified acceptable/guideline and satisfies the 

guideline requirement for a developmental toxicity study (OPPTS 870.3700; OECD 414). 

Reproductive Toxicity: In a two-generation reproduction study, INY-6202 (quizalofop 99.1% 

a.i.) was administered to Crl:CD Sprague-Dawley rats (23/sex/dose) in the diet at dose levels of 

0, 25, 100, or 400 ppm (equivalent to 0, 1.25, 5.0, or 20 mg/kg bw/day, respectively). After 70 

days on test, the F0 generation was bred to produce F1a and F1b litters. At weaning, randomly

selected F1a rats were fed diets containing INY-6202 for 80 days and then mated to produce F2a 

and F2b litters. After litter production, ten rats per sex per dose in the F0 and F1a generations had 

reproductive tissues examined. Ten F2b weanlings per sex per dose were subjected to gross 

pathological examination. Those from the control and high-dose (400 ppm) groups were 

subjected to complete microscopic examination. 

For parental toxicity, significant decreases of body weight and body weight gains were observed 

in both F0 and F1a males and F1a females at 400 ppm compared to the control. No 
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treatment-related deaths or clinical observations were observed in the parental rats. The 

LOAEL of parental systemic toxicity is 400 ppm (equivalent to 20 mg/kg bw/day), based on 

decreased body weights and body weight gains. The NOAEL is 100 ppm (equivalent to 5.0 

mg/kg bw/day). 

For offspring toxicity, pup body weights at the high-dose (400 ppm) were significantly lower 

than controls in F1a and F1b pups from birth throughout lactation, and F2a and F2b pup weights 

were significantly reduced starting at day 7 and day 4, respectively. Significantly increased 

absolute and relative liver weights were observed in the F2b weanlings of both sexes at 100 and 

400 ppm. Increased relative kidney and heart weights were also observed at 400 ppm compared 

to the control. Mean relative spleen weight was decreased at 400 ppm. Histopathological 

examination of hepatocytes from F2b weanlings revealed distinct eosinophilic granular 

cytoplasm and decreases in cytoplasmic basophilia and glycogen accumulation in the 100 and 

400 ppm groups. Previously HED had established a LOAEL at 100 ppm based on increased 

incidence of eosinophilic changes in the liver of F2 weanlings. However, the HED later 

questioned the biological significance of these findings and stated that this endpoint in adults 

(eosinophilic changes) would not be considered appropriate for use in the regulation of 

quizalofop ethyl (TXR# 012373, J. Rowland, 10/24/1997). The study author stated that 

hepatocytes had distinct eosinophilic changes and were considered indicative of proliferation of 

the smooth endoplasmic reticulum. Therefore, the LOAEL of offspring toxicity is revised to 400 

ppm (20 mg/kg bw/day) based on decreased pup weights. The NOAEL is 100 ppm (5 mg/kg 

bw/day). For reproductive toxicity, a significantly lower percentage of pups born alive were 

observed in the F1a and F2a litters of the 400 ppm group. Fertility rates were comparable in all 

groups of both generations except the low-dose F0 males and females, which had significantly 

reduced fertility rates when compared to the control at the first mating. All pregnant females 

successfully delivered live pups and maintained their litters until weaning. Clinical observation 

of the offspring showed an increased incidence of hematomas in the F1b pups at 25, 100, and 

400 ppm and F2a pups at 100 and 400 ppm. However, the increased incidence of hematomas 

was not considered a reproductive effect because it was not dose-related, and was not 

consistently observed in all generations and in other studies. The reproductive LOAEL is 400 

ppm (20 mg/kg bw/day), based on decreased percentage of pups born alive. The reproductive 

NOAEL is 100 ppm (5 mg/kg bw/day). This study is acceptable/guideline and satisfies the 

guideline requirement for a 2-generation reproductive study (OPPTS 870.3800; OECD 416). 

Additional Information from Literature Sources: No additional relevant toxicity studies from 

published literature were identified. 

Pre- and/or Postnatal Toxicity and Determination of Susceptibility: There is no evidence of 

increased qualitative or quantitative susceptibility following in utero and/or pre/post-natal exposure 

in the developmental toxicities in rats and rabbits and two-generation reproduction study in rats. 

Degree of Concern Analysis and Residual Uncertainties for Pre and/or Post-natal 

Susceptibility: There are no concerns and no residual uncertainties for pre- and postnatal toxicity. 
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Recommendation for a Developmental Neurotoxicity Study: The HED has determined that a 

developmental neurotoxicity study is not required based on the lack of evidence of 

neurotoxicity in the submitted studies. 

4.4.4 Residual Uncertainty in the Exposure Database

Based on the available data, the 10x FQPA SF to account for enhanced sensitivity of infants and 

children (as required by FQPA) was reduced to 1x. The HED has confidence that the risk 

assessment conducted with no additional safety factor will provide a reasonable certainty of no 

harm to the safety of infants and children.

4.5 Toxicity Endpoint and Point of Departure Selections

4.5.1 Dose-Response Assessment

Acute Reference Dose (aRfD) : There were no effects observed in oral toxicity studies that 

could be attributable to a single dose (exposure). In addition, there is no developmental or 

reproductive toxicity of concern for quizalofop ethyl. Therefore, no appropriate endpoint or 

dose that is appropriate for assessing acute risk has been selected for quizalofop ethyl. 

Chronic Reference Dose (cRfD): In a combined chronic toxicity/carcinogenicity study in rats; 

(MRID No.: 00146682), NC-302 (quizalofop ethyl, 99.1%, a.i.) was administered to SpragueDawley CD rats (50/sex/dose) at dose levels of 0, 25, 100, or 400 ppm (0, 0.9, 3.7, or 15.5 

mg/kg/day for males and 0, 1.1, 4.6, or 18.6 mg/kg/day for females, respectively) in their diet 

for 104 weeks. There were no significant treatment-related clinical signs. Body weights and 

food consumption were comparable among the dosed and control groups. The hematological 

values showed a trend of mild anemia or red blood cell destruction in the 100 ppm males early in 

the study and in the 400 ppm females late in the study. Clinical chemistry examination showed a 

significantly elevated alkaline phosphatase level in the 400 ppm males at all intervals and in the 

400 ppm females at Week 101. Significant increases in liver weights were observed in the 400 

ppm males and females at all intervals. Gross pathology showed an increased 

numbers of liver masses in the 100 and 400 ppm males and females. Histopathology showed an 

increased incidence of generalized hepatocytic enlargement in the 400 ppm males and 

cytoplasmic eosinophilia of the centrilobular hepatocytes in the 400 ppm group of both sexes. 

Increased incidence of slight/minimal centrilobular enlargement of the liver was observed in the 

100 ppm and 400 ppm males and females. 

The LOAEL is 100 ppm (3.7 mg/kg/day for males and 4.6 mg/kg/day for females) based on 

increased incidence of centrilobular enlargement of the liver in both sexes and mild anemia in 

the males. The NOAEL is 25 ppm (0.9 mg/kg/day for males and 1.1 mg/kg/day for females). 

The combined chronic toxicity/carcinogenicity study in the rat is classified acceptable/guideline 

and satisfies the guideline requirement for a chronic toxicity/carcinogenicity study (OPPTS 

870.4300; OECD 453). 
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Dose and Endpoint for Establishing the cRfD: 0.9 mg/kg/day (NOAEL) based on increased 

incidence of centrilobular enlargement of the liver in both sexes and mild anemia in the males at 

3.7 mg/kg/day (LOAEL). 

Uncertainty Factor(s): 100 (10x for interspecies extrapolation and 10x for intra-species variations). 

Comments about Study/Endpoint/Uncertainty Factor: The selected dose/endpoints are appropriate 

for the route and duration of exposure. 

cRfD = 0.9 mg/kg (NOAEL) = 0.009 mg/kg/day

 100 (UF) 

Incidental Oral Exposure: Quizalofop ethyl is not registered for residential uses. Based on this 

use pattern (low exposure), there is no incidental oral exposure; therefore, no short-term (1-30 

days) and intermediated-term (1-6 months) end points were selected and no risk assessments are 

required. 

Dermal Exposure: (All Durations): There was no dermal or systemic toxicity identified in a 21-

day dermal toxicity study in rabbits. The NOAEL was 2000 mg/kg/day at the maximum dose 

tested (MDT). No appropriate endpoint was identified. Therefore, a risk assessment via this route 

is not required. Furthermore, no endpoints from the available data suggest that a dermal risk 

assessment should be done by extrapolating from an oral NOAEL, in order to be protective of 

effects not typically measured in dermal toxicity studies. 

The results of a dermal absorption study in rats (MRID 00146679) indicated that with a 10-hour 

exposure at doses of 0.19, 1.9, or 19 mg/rat, the percent of absorption was 8.38, 3.27, and 2.9% of 

the applied dose, respectively. A dermal absorption factor is not applicable since dermal risk 

assessments are not required. 

Inhalation Exposure (All Durations): The LC50 value for quizalofop ethyl is 4.8-5.8 mg/L which 

place it Toxicity Category IV indicative of low acute inhalation toxicity. For longer exposure 

durations, based on a comparison of inhalation and oral points of departure for a series of 89 

pesticides, and on the maximum inhalation exposure expected from occupational and residential 

uses of quizalofop-P-ethyl, HED concludes that an inhalation toxicity study on quizalofop-Pethyl is unlikely to result in a point of departure indicating risks of concern. Therefore, a risk 

assessment via this route of exposure is not required. 

Margins of Exposure: For residential and occupational exposures, no risk assessments are 

required. 

4.5.3 Cancer Classification and Risk Assessment Recommendation

Quizalofop ethyl is classified as category D (Not classifiable as to human carcinogenicity). 
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Carcinogenicity Study in Rats 

See the discussion on cRfD under section 4.3 

Discussion of Tumor Data: Neoplastic histopathology showed an increased incidence of benign 

and malignant liver cell tumors in both sexes with a significant dose-related trend for 

hepatocellular carcinoma in females. However, no increase of liver hyperplasia or adenoma 

was seen. The Registrant asked the tumor pathology data to be re-evaluated by the 

Environmental Pathology Laboratory (EPL) and the findings were revised as follows (a) an 

increased number of adenomas in all groups and (b) a reduction in the number of carcinomas in the 

mid- and high-dose groups. The HED Carcinogenicity Peer Review Committee subsequently 

concluded that quizalofop ethyl did not appear to be associated with an increase in liver carcinoma 

in female CR-SD rats (TXR# 007983, W. Phang, 6/11/1987). 

Carcinogenicity Study in Mice 

In a carcinogenicity study (MRID 00146684), NC-302 (quizalofop ethyl, 99%, a.i.) was 

administered to CD-1 mice (70/sex/dose) at dose levels of 0, 2, 10, 80, or 320 ppm (equivalent to 

0, 0.3, 1.4, 11.4 or 45.7 mg/kg/day by a standard conversion factor) in diet for 78 weeks. Two 

subgroups of animals (10/sex/dose) were designated as satellite groups for interim sacrifices at 

weeks 26 and 52. 

There was a significant trend towards decreased survival in the males with a significant lower 

survival seen at 320 ppm compared to controls. Female survival was comparable in the dosed 

and control groups. Increased body weights, hematology and clinical chemistry parameters 

were observed in the 80- and 320-ppm groups. A statistically significant decrease in testicular 

weight was noted at the terminal sacrifice in males that received 320 ppm. Increased incidences 

of bilateral testicular atrophy were observed at 80 and 320 ppm. In both sexes of 80 and 320-

ppm treated mice, hepatotoxicity was evident with enlarged and dark livers along with 

histopathology observations. The NOAEL was 10 ppm (1.4 mg/kg/day) and the LOAEL was 

80 ppm (11.4 mg/kg/day) based on increased incidence of bilateral testicular atrophy, enlarged 

liver and histopathology findings indicative of hepatotoxicity in the liver. The carcinogenicity 

study in the mouse is classified acceptable/guideline and satisfies the guideline requirement for a 

carcinogenicity study (OPPTS 870.4200; OECD 4531). 

Discussion of Tumor Data: Increased incidences of ovarian tumors in females and liver tumors in 

males were observed at the high-dose only. The EPA Carcinogenicity Peer Review 

Committee reevaluated the study and determined that the tumor incidence of ovarian stromal 

tumors in female mice was not significantly elevated and was not considered a compoundrelated effect based on historical control data and the absence in findings of hyperplasia of the 

ovary, signs of endocrine activity related to ovarian function, and dose-response relationship 

with respect to the incidences observed. The Committee also diminished the weight of 

evidence for an effect of test material to produce liver tumors based on the historical control 

data and the lack of increased incidences of liver adenoma and liver hyperplasia. Also, the liver 

tumors observed in this study did not occur in a strictly dose-related manner, they were seen 

only at the high dose level which exceeded a MDT level.
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Adequacy of the Dose Levels Tested: The Cancer Peer Review Committee has determined that the 

highest dose tested in males exceeded a MDT level based on increased mortality rate 

(TXR# 007983, W. Phang, 6/11/1987). 

Mutagenicity: The Cancer Peer Review Committee determined that mutagenicity studies did not 

demonstrate mutagenic potential for quizalofop ethyl (TXR# 007983, W. Phang, 

6/11/1987). Results are summarized as follows: negative for recombinant assays using B. subtilis

M-45 and H-17, negative for revision assays using E. coli WP2 and S. typhimurium TA1535, 

TA1537, TA1538, TA98, TA100 strains, negative for chromosome aberration in the CHO cells, and 

negative for unscheduled DNA synthesis (UDS). 

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

Assessment

Table 4.5.4.1 Summary of Toxicological Doses and Endpoints for Quizalofop-P-ethyl for Use in Dietary and 

Non-Occupational 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 

– all 

populations

No appropriate endpoint was identified. There were no effects observed in oral toxicity studies 

that could be attributed to a single-dose exposure.

Chronic 

Dietary (All 

Populations)

NOAEL= 

0.9 

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF= 1x

Chronic RfD 

= 0.009

mg/kg/day

cPAD = 0.009 

mg/kg/day

Chronic toxicity/Carcinogenicity study in 

rats. 

LOAEL = 3.7 mg/kg/day based on 

increased incidence of centrilobular 

enlargement of the liver in both sexes and 

mild anemia in males. 

Incidental Oral No endpoint was selected as no residential uses are under registration.

Dermal – all 

durations No appropriate endpoint was identified and a risk assessment via this route is not required.

Inhalation – all 

durations No appropriate endpoint was identified and a risk assessment via this route is not required.

Cancer (oral, 

dermal, 

inhalation)

Category D. Not classifiable as to human carcinogenicity.

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). FQPA SF = FQPA Safety Factor. PAD = 

population adjusted dose (a = acute, c = chronic). RfD = reference dose.
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5.0 Dietary Exposure and Risk Assessment 

5.1 Metabolite/Degradate Residue Profile

5.1.1 Summary of Plant and Animal Metabolism Studies

The qualitative nature of the residue in plants is adequately understood based on previously

submitted plant metabolism studies with soybean, cotton, tomatoes, potatoes, and sugar beets. 

The metabolism studies indicate that quizalofop ethyl does not accumulate but is rapidly

hydrolyzed at the ethyl ester to form quizalofop acid. The acid then undergoes cleavage of the 

enol ether linkage between the phenyl and quinoxalinyl rings and/or cleavage of the ether linkage 

between the isopropanoic group and the phenyl ring to form phenols. Metabolism studies with 

soybeans demonstrated that the racemic mixture of quizalofop ethyl and the resolved Renantiomer, quizalofop-P-ethyl have nearly identical pathways (DP# 182751, J. Stokes, 7/15/93). 

To support the current petition to uses on genetically modified corn, a metabolism study in 

genetically modified corn containing the AAD-1 gene was submitted. The petitioner proposed 

that the metabolism of quizalofop-P-ethyl ester proceeds from the ester to the acid and continues 

through incorporation of the radiolabeled carbon into natural plant constituents, such as lignin 

and cellulose.

The nature of the residue in livestock is adequately understood based on metabolism studies with 

goats and poultry. The studies indicate that quizalofop ethyl is metabolized in livestock via 

hydrolysis to quizalofop acid which then undergoes methylation to form quizalofop methyl ester. 

No phenols were detected in either the goat or hen matrices, indicating that cleavage of the ether 

linkages of quizalofop does not occur. In hens quizalofop-P acid is utilized in fatty chain 

elongation to form quizalofop-pentanoic acid. 

Refer to section 4.2 for a brief description of metabolism studies in rats.

5.1.3 Residues of Concern Summary and Rationale

Nature of the Residue in Plants: The qualitative nature of the residue in plants is adequately 

understood based on previously submitted plant metabolism studies with soybean, cotton, 

tomatoes, potatoes, sugar beets, barley, flaxseed, sunflower and wheat. In addition, adequate 

metabolism studies with genetically modified field corn were submitted to support the proposed 

new uses. For the risk assessment, HED has determined that the residues of concern in plant 

commodities are quizalofop-P-ethyl, it metabolite quizalofop-P acid, and the S-enantiomers of 

both compounds, each expressed as quizalofop-P-ethyl. 

Nature of the Residue in Animals: The qualitative nature of the residue in livestock is 

adequately understood based on metabolism studies with goats and poultry. The studies 

indicated that quizalofop ethyl is metabolized in livestock via hydrolysis to quizalofop acid 

which then undergoes methylation to form quizalofop methyl ester. No phenols were detected 

in either goat or hen commodities, indicating that cleavage of the ether linkages of quizalofop 
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Page 24 of 34

does not occur. The residues of concern in livestock commodities are quizalofop ethyl, 

quizalofop methyl, and quizalofop acid, expressed as quizalofop ethyl.

Nature of the Residue in Rotational Crops: In a confined accumulation study, [Phenyl14C]-

and [quinoxaline14C]-quizalofop ethyl treated soils were aged 30 and 62 days before planting 

with the rotational crops red beets, lettuce, wheat, peanuts, and cotton. The petitioner has 

characterized and identified over 50% of the residue in each of the rotational crops from the 

phenyl- and quinoxaline-labeled quizalofop ethyl soil treatment and has confirmed the 

hydrolysis of the ethyl ester, and the cleavage of the enol and ether linkage metabolic pathways. 

The data support a 120-day plant-back interval. The nature of the residue in rotational crops is 

adequately understood and is the same as identified above for tomatoes, cottonseed, soybeans, 

and sugar beets. The residues of concern are quizalofop ethyl and its acid metabolite (D219672 

and D222000, Griffith, F. D, 1/26/1996).

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

Primary Crop

Quizalofop-P-ethyl, 

quizalofop-P, and the Senantiomers of both, 

expressed as quizalofop ethyl

Quizalofop-P-ethyl, 

quizalofop-P, and the Senantiomers of both, 

expressed as quizalofop ethyl

Rotational Crop Quizalofop ethyl and 

quizalofop Not Applicable.

Livestock

Ruminant Quizalofop ethyl, quizalofop 

methyl, and quizalofop acid, 

expressed as quizalofop ethyl

Quizalofop ethyl, quizalofop 

methyl, and quizalofop acid, 

Poultry expressed as quizalofop ethyl

Drinking Water Quizalofop ethyl and 

quizalofop acid Not Applicable

5.2 Food Residue Profile

Crop Field Trials: The submitted residue data for field corn commodities (forage, grain, and 

stover) are tentatively considered to be adequate, pending submission of storage stability data 

demonstrating the stability of quizalofop-P-ethyl and quizalofop acid in/on field corn forage, 

grain, and stover. The number and locations of crop field trials are in accordance with OCSPP 

Guideline 860.1500. The field trials reflect the proposed use pattern. The maximum total

quizalofop-P-ethyl residues [sum of quizalofop-P-ethyl and quizalofop acid residues (as parent 

equivalents)] were <0.02 ppm in/on forage and grain and <0.022 ppm in/on stover. Using the 

OECD MRL calculator, the recommended tolerances are 0.02, 0.02, and 0.03 ppm in/on corn 

forage, grain, and stover, respectively. The forage and grain recommendations are higher than 

the tolerance levels proposed by the petitioner and the stover recommendation is identical to the 

tolerance level proposed by the petitioner.
Quizalofop-P-ethyl Human Health Risk Assessment DP No. 384660 and 386678

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The submitted residue data for sorghum commodities (forage, grain, and stover) are adequate to 

satisfy data requirements. The sorghum field trials reflected the maximum proposed application 

rates and the proposed PHIs. The maximum total quizalofop-P-ethyl residues [sum of 

quizalofop-P-ethyl and quizalofop acid residues (as parent equivalents)] were <0.180 ppm in/on 

forage, <0.158 ppm in/on grain, and <0.266 ppm in/on stover. Using the OECD MRL calculator, 

the recommended tolerances are 0.20, 0.20, and 0.30 ppm in/on sorghum forage, grain, and 

stover, respectively. These recommendations are identical to the tolerance levels proposed by 

the petitioner for sorghum forage and grain. The tolerance level recommendation for sorghum 

stover is slightly lower than the level (0.35 ppm) proposed by the petitioner.

No residue data were submitted to support the proposed use on mustard seed and other members 

of the rapeseed subgroup 20A, except flaxseed. The available field trial data for canola seed, the 

representative crop of the rapeseed subgroup 20A, may be translated to support the proposed 

uses on mustard seed and other members of the rapeseed subgroup 20A, except flaxseed. These 

data are adequate to fulfill data requirements and reflect ~0.8-1.5x the maximum proposed 

seasonal application rate for the EC formulation with 38- to 74-day PHI. The data for 0.8x and 

1.5x was analyzed to recommend a tolerance that may support use of the 0.88 lb ai /gal EC 

formulation.

Table 5.2. Summary of Residues from the Crop Field Trials with Quizalofop-P-ethyl.

Crop Matrix Applic. Rate

(lb ai/A)

PHI 

(days)

Residues (ppm)

n Mean

Std. 

Dev. HAFT 1 Min. Max.

Field Corn containing DAS-40278-9

(Proposed Use: 0.083 lb ai/A total application rate, 30-day PHI for forage; plus adjuvant)2

Corn, field, early forage 0.078-0.088 32-47 24 0.02 --- <0.02 <0.02 <0.02

Corn, field, forage 44-83 24 0.02 --- <0.02 <0.02 <0.02

Corn, field, grain 79-144 25 0.02 --- <0.02 <0.02 <0.02

Corn, field, stover 79-144 25 0.02 --- <0.022 <0.02 <0.022

Sorghum grain containing the DuPontTM INZENTM AII Herbicide Tolerance Trait

(Proposed Use: 0.138 lb ai/A total application rate, 30-day PHI for forage and 45-day PHI for grain and stover;

plus adjuvant)

Sorghum, forage 0.136-0.145 25-32 13 0.112 0.019 <0.169 <0.104 <0.180

Sorghum, grain 29-49 12 0.111 0.014 <0.149 <0.104 <0.158

Sorghum, stover 42-56 13 0.129 0.040 <0.212 <0.104 <0.266

Rapeseed Subgroup 20A, Except Flaxseed, Seed3, 4

(Proposed Use: 0.124 lb ai/A total application rate, 60-day PHI; plus adjuvant)

Canola, seed 0.094 38-74 9 0.19 0.21 0.65 <0.05 0.7

Canola, seed 0.188 38-74 9 0.39 0.46 1.5 <0.05 1.5

1 HAFT = highest-average-field-trial.

2 Except for sample min/max, values reflect per trial averages; n = no. of field trials. For calculation of median, mean, and 

standard deviation, the LOQ (0.01 ppm) was used for any results reported as ND (0.003 ppm) or between the LOD and LOQ.

3 Canola data available from a previous petition (PP#5F4545/FAP#6H5737; DP#s 220476, 220478, 220480, F. Griffith, 2/21/96)

4 The Rapeseed Subgroup 20A includes Borage, Crambe, Cuphea, Echium, Gold of Pleasure (Camelina), Hare’s ear mustard, 

Lesquerella, Lunaria, Meadowfoam, Milkweed, Mustard seed, Oil Radish, Poppy seed, Rapeseed (Canola), Sesame, and Sweet 

Rocket.
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Processing Studies: Adequate processing data for corn have been submitted, pending 

submission of storage stability data demonstrating the stability of quizalofop-P-ethyl and 

quizalofop acid in/on field corn processed commodities. Tolerances for the processed 

commodities of corn are not needed for the purpose of this petition based on the results of 

processing trials which showed that residues of quizalofop-P-ethyl and quizalofop acid (as parent 

equivalents) were <LOQ in/on field corn grain RAC (treatment at ~2x the proposed maximum 

seasonal rate), and in field corn processed commodities (starch, refined oil (wet and dry milling), 

meal, grits, flour, and AGF). The registrant explained that phytotoxicity concerns preclude corn 

processing studies at higher treatment rates.

Adequate processing data for sorghum have been submitted. The processing data indicate that 

total quizalofop-P-ethyl residues concentrate in sorghum AGF. Based on the processing factor, 

3.4x, and the HAFT for sorghum grain, 0.149 ppm, expected residues in sorghum AGF 

following treatment at 1x would be 0.507 ppm. Because this value is greater than the 

recommended 0.2-ppm tolerance for sorghum grain, a tolerance is needed for total quizalofop-Pethyl residues in/on sorghum, grain, aspirated grain fractions. A tolerance of 1.0 ppm would be 

appropriate. 

No new processing data were submitted in support of the label amendment request to expand the 

use of quizalofop on rapeseed meal that would cover the rapeseed subgroup 20A, except 

flaxseed). Acceptable processing data were previously submitted and reviewed for canola seed, 

the representative crop of subgroup 20A, under PP# 5F4545/FAP# 6H5737 (DP#s 220476, 

220478, and 220480, F. Griffith, 2/21/96). Based on the available canola processing data, a 

tolerance for canola meal was established at 1.5 ppm; a tolerance was not required for refined oil. 

The canola processing data was used to recommend a tolerance for the rapeseed, meal of 2.0 

ppm by adjusting for the proposed application rate. 

Rotational Field Trials: The available confined/field rotational crop data indicate that a 120-day

plant back interval (PBI) is required for all crops other than those with registered uses.

Storage Stability: The storage duration of the samples of the submitted crop field trial studies 

with sorghum are supported by adequate storage stability data of the residues of concern. 

However, storage stability data for quizalofop P-ethyl and quizalofop acid in/on field corn and 

processed commodities are not currently available. The petitioner indicated that a storage 

stability study is in progress. Storage stability data for quizalofop ethyl and quizalofop in/on 

various matrices, including cotton, soybean, and wheat commodities, have been submitted 

previously. The available wheat storage stability data are tentatively considered adequate to 

support submitted crop field trial on corn. Storage stability data were not provided for the corn 

processed commodities and are required to support the processing studies. When the storage 

stability study on corn is submitted, the adequacy of the storage stability data will be reevaluated.
Quizalofop-P-ethyl Human Health Risk Assessment DP No. 384660 and 386678

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Milk, Meat, Poultry and Eggs: Adequate ruminant and poultry feeding studies were submitted 

previously. These studies indicate that tolerances are needed for livestock commodities to 

support the current and proposed uses of quizalofop-P-ethyl. The maximum reasonable dietary

burdens (MRDBs) of quizalofop-P-ethyl to livestock have been re-calculated using the registered 

and proposed uses. Based on the calculated MRDBs, the established tolerances are adequate for 

all livestock commodities.

5.3 Water Residue Profile

The Agency does not have monitoring data available to perform a quantitative drinking water 

risk assessment for quizalofop-P-ethyl at this time. A Tier II drinking water assessment prepared 

by the Environmental Effects and Fate Division (EFED) is summarized below (S. Wente, 

07/19/2011, D384661).

A Tier II drinking water assessment of surface water was performed based on Index Reservoir 

settings, using the linked PRZM-EXAMs models. The sorghum application scenario was used to 

predict an estimated drinking water concentration (EDWC) of 2.006 ppb for chronic exposure. 

For ground water sources, the SCIGROW model was used to predict an EDWC of 1.29 ppb for 

chronic exposure. Since the surface water concentration was the highest, the chronic dietary risk 

assessment was conducted assuming a residue of 0.002 ppm for all water sources (direct and 

indirect). The EDWCs obtained by these two models are summarized in Table 5.3.

Table 5.3. Drinking Water EDWCs for Quizalofop ethyl

Model Used Chronic (parts/billion)

PRZM/EXAMs 2.006

SCIGROW 1.29

5.4 Dietary Risk Assessment

5.4.1 Description of Residue Data Used in Dietary Assessment

An acute dietary exposure assessment was not prepared because an endpoint attributable to a 

single oral dose was not identified from the toxicity studies of quizalofop ethyl; therefore, an 

aRfD was not established. 

A chronic dietary risk assessment was conducted using the Dietary Exposure Evaluation Model 

- Food Consumption Intake Database (DEEM-FCID, ver. 2.03). DEEMTM-FCID 

incorporates the food consumption data from the USDA’s Continuing Surveys of Food Intakes 

by Individuals (CSFII; 1994-1996 and 1998). The chronic analysis incorporated tolerance level 

residues for all commodities and 100 %CT was assumed. DEEMTM (ver 7.78) default 

processing factors were assumed when applicable. The assessment included existing food uses 

as well as the newly proposed tolerances to be established for Section 3 uses on barley, wheat, 

sunflower and flaxseed, as well as the PRZM-EXAMs modeled chronic surface water point 

estimate generated based on the MI dry pea application scenario. Table 5.4.6 summarizes the
Quizalofop-P-ethyl Human Health Risk Assessment DP No. 384660 and 386678

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dietary exposures and the corresponding %cPADs for the population subgroups (D395387, S. 

Tadayon, 10/25/2011).

5.4.2 Percent Crop Treated Used in Dietary Assessment

The chronic analysis was based 100 %CT for all food commodities.

5.4.3 Acute Dietary Risk Assessment

No acute endpoint has been identified; therefore, an acute dietary assessment was not performed. 

5.4.4 Chronic Dietary Risk Assessment

The chronic analysis was based on conservative assumptions (tolerance level residues and 100 

%CT) for food commodities. A modeled drinking water estimate was used is the assessment. 

The drinking water assessment of surface water was performed to assess drinking water exposure 

for quizalofop-P-ethyl in support of field corn and sorghum. Since the drinking water estimate 

was generated using the site/scenario which produced the highest estimated surface water 

concentration, and since conservative assumptions were used for food, HED concludes that the 

exposure estimates provided in this document are highly conservative and is not likely to 

underestimate risk. 

The chronic dietary risk estimates are 29 % cPAD and are therefore below HED’s level of 

concern (children 1-2 years old were the most highly exposed population).

5.4.5 Cancer Dietary Risk Assessment

Quizalofop-P-ethyl was classified as "not likely" to be a human carcinogen, therefore no cancer 

assessment was needed.

5.4.6 Summary Table

The chronic dietary risk estimates are 29 % cPAD (See Table 5.4.6) and are therefore below 

HED’s level of concern (children 1-2 years old were the most highly exposed population).

Table 5.4.6 Summary of Chronic Dietary Exposure and Risk for Quizalofop-P-ethyl (drinking water included)

Population Subgroup cPAD (mg/kg/day)

Chronic

Exposure (mg/kg/day) %cPAD

General U.S. Population

0.009

0.001025 11

All Infants (< 1 year old) 0.002477 28

Children 1-2 years old 0.002636 29*

Children 3-5 years old 0.002315 26

Children 6-12 years old 0.001590 18

Youth 13-19 years old 0.000978 11

Adults 20-49 years old 0.000803 9

Adults 50+ years old 0.000685 8

Females 13-49 years old 0.000767 9

* Children 1-2 years old were the most highly exposed population
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6.0 Residential (Non-Occupational) Exposure/Risk Characterization

Quizalofop-P-ethyl doesn’t have either proposed or registered residential uses.

6.5 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, but, to a lesser extent, could also be a 

potential source of exposure from the ground application method employed for quizalofop-Pethyl. 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 (see the Agency’s Spray Drift website for more information at 

http://www.epa.gov/opp00001/factsheets/spraydrift.htm). 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.

7.0 Aggregate Exposure/Risk Characterization

Since quizalofop ethyl has no registered or proposed residential uses which would result in 

residential exposures, the chronic dietary exposure analysis incorporating exposures from food 

and drinking water, presented in Table 5.4.6 represents the aggregate chronic risk assessment.

8.0 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 quizalofop-P-ethyl and any other substances and quizalofop-P-ethyl 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 quizalofop-P-ethyl 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/.
Quizalofop-P-ethyl Human Health Risk Assessment DP No. 384660 and 386678

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9.0 Occupational Exposure/Risk Characterization

A separate memorandum summarizes HED's assessment of the occupational exposure and risks 

of use of quizalofop ethyl as an herbicide (D392851, S. Tadayon, 9/1/2011). Since no shortterm dermal and inhalation toxicity endpoints were identified for estimating the occupational 

exposures to handlers and post-application workers, no quantitative risks were calculated. HED 

has no concerns for occupational exposures associated with the proposed uses. Quizalofop 

ethyl has a 12-hour (REI) established under the WPS and its acute toxicity categories are IV for 

both dermal and inhalation routes of exposures. 

Occupational/Commercial Postapplication Inhalation Section

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

assessment was not performed for quizalofop-P-ethyl at this time primarily because of the low 

acute inhalation toxicity (Toxicity Category III and IV), low vapor pressure (8.3 x 10-10 mm Hg), 

and the low proposed use rate (0.83 lb ai/A). However, there are multiple potential sources of 

post-application inhalation exposure to individuals performing post-application activities in 

previously treated fields. These potential sources include volatilization of pesticides and 

resuspension of dusts and/or particulates that contain pesticides. 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, 2010 

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

process of evaluating the SAP report as well as available post-application inhalation exposure 

data generated by the Agricultural Reentry Task Force and may, as appropriate, develop policies 

and procedures, to identify the need for and, subsequently, the way to incorporate occupational 

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 occupational 

post-application inhalation exposure assessment for quizalofop-P-ethyl.
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10.0 References

Risk Assessments

Quizalofop-P-ethyl: Human health risk assessment for new uses on barley, flaxseed, sunflower 

and wheat, D310869, S. Oonnithan, 08/10/2006.

Dietary Exposure Memorandum

Quizalofop-P-ethyl. Chronic dietary exposure assessment to support section 3 registration for 

use on corn, rapeseed and sorghum, D395387, 10/25/2011.

Drinking Water Memoranda

Drinking water exposure for quizalofop-P-ethyl in support of propagation of herbicide-tolerant 

field corn and sorghum, D384661, S.P. Wente, 07/19/2011.

Residue Chemistry Data Review

Quizalofop-P-ethyl. Petition for Registration of New Use on Corn (PP#1F7822) and Sorghum 

Grain, and Rapeseed Subgroup 20A, Except Flaxseed (PP#0E7802). Summary of Analytical 

Chemistry and Residue Data., D395630, I. Negrón-Encarnación, 15/Nov/2011.

Occupational and Residential Exposure Assessment

Quizalofop -P- ethyl: Occupational Risk Assessment for the Proposed Uses on Corn, Sorghum, 

Grain, and Rapeseed Subgroup 20A (except Flaxseed) seed, D392851, S. Tadayon, 09/10/2011.
Quizalofop-P-ethyl Human Health Risk Assessment DP No. 384660 and 386678

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Appendix A. Toxicology Profile and Executive Summaries

A.1 Toxicology Data Requirements

The requirements (40 CFR 158.340) for non food and food uses for quizalofop-P-ethyl are 

below. Use of the new guideline numbers does not imply that the new (1998) guideline protocols 

were used.

Study

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 90-Day Inhalation..........................................................

yes

yes

no

no

no

yes

yes

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 

in CHO cells.....................................................................................

870.5500. Bacterial DNA damage or repair test (recombinant 

assay in B. subtilis). 

870.5550 Mutagenicity—Unscheduled DNA synthesis.................

yes

--

yes

yes

yes

yes

--

yes

yes

yes

870.6100a Acute Delayed Neurotoxicity (hen)...............................

870.6100b 90-Day Neurotoxicity (hen)...........................................

870.6200a Acute Neurotoxicity Screening Battery (rat) .................

870.6200b 90-Day Neurotoxicity Screening Battery (rat)...............

870.6300 Develop. Neurotoxicity .................................................

no

no

no

no

no

-

-

-

-

-

870.7485 General Metabolism ......................................................

870.7600 Dermal Penetration........................................................

870.7800 Immunotoxicity .............................................................

yes

no

Conditionally

yes

no

yes
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A.2 Toxicity Profiles

Table A.2.1 Acute Toxicity Profile of Quizalofop ethyl.

OPPTS 

Guidelin

e

Study Type MRID Results

Toxicity 

Category

870.1100 Acute oral toxicity / rat 00146669 LD50 = 1670 mg/kg (M)

 1480 mg/kg (F)

III

870.1200 Acute dermal toxicity / rat 00146670 LD50 => 5000 mg/kg IV

870.1300 Acute inhalation toxicity / rat 00146674 LC50 = 4.8-5.8 mg/L IV

870.2400 Primary eye irritation / rabbit 00146671 Not an irritant IV

870.2500 Primary dermal irritation / 

rabbit

00146672 Negative IV

870.2600 Dermal sensitization / 

guinea pig

00146673 Non-Sensitizer --

Table A.2.2 Subchronic, Chronic and Other Toxicities Profile for Quizalofop ethyl.

Guideline No./ 

Study Type/

MRID Nos.

Doses/Classification

Results 1

870.3100

Subchronic Oral

- Rat

00128216 (1982)

(0, 40, 128, 1280 ppm)

M: 0, 2.6, 8.4, 82.9 mg/kg/day

F: 0,3.0, 9.7, 93.6 mg/kg/day

Acceptable/Guideline

NOAEL=8.4/9.7 (M/F) mg/kg/day

LOAEL= 89.2/93.6 (M/F) mg/kg/day based on 

decreased body weight gains, increased liver 

weight and centrilobular liver cell enlargement.

870.3150

Subchronic Oral

- Dog

00127969 (1982)

(0, 25, 100, 400 ppm)

0, 0.63, 2.5, 10 mg/kg (M/F)

(by a standard conversion factor)

Acceptable/Guideline

NOAEL= 2.5 mg/kg/day

LOAEL= 10 mg/kg/day based on increased 

incidence of testicular atrophy.

870.3200

28-Day dermal 

toxicity- Rabbit

00146677 (1983)

0, 125, 500, 2000 mg/kg/day 

(M/F)

Acceptable/Guideline

NOAEL= 2000 mg/kg/day (highest dose tested 

[HDT])

870.3700a

Prenatal, 

developmental -

Rat 

00128206 (1983)

0, 30, 100, 300 mg/kg/day

(GD 2 6-15)

Acceptable/Guideline

Maternal: NOAEL= 30 mg/kg/day; LOAEL= 

100 mg/kg/day based on decreased body 

weight gains and food consumption.

Developmental: NOAEL= 300 mg/kg/day 

(HDT).

870.3700b

Prenatal 

developmental 

- NZW Rabbit 3 

40370502 (1985)

0, 7, 20, 60 mg/kg/day (GD 7-19)

Range-finding study

0, 7, 25, 60, 75 mg/kg/day (GD 7-

19), Acceptable/Guideline

Maternal: NOAEL= 20 mg/kg/day, LOAEL= 

60 mg/kg/day based on decreased body weight 

gains and food consumption.

Developmental: NOAEL= 60 mg/kg/day 

(HDT).

870.3800

Reproduction and 

fertility effects

- Rat

00153351 (1985), 40242502 

(1987)

(0,25, 100, 400 ppm)

0, 1.25, 5.0, 20 mg/kg/day (M/F)

(by a standard conversion factor)

Acceptable/Guideline

Parental/Systemic:

NOAEL= 5 mg/kg/day; LOAEL= 20 

mg/kg/day based on decreased body weight and 

body weight gains.

Reproductive:

NOAEL=5 mg/kg/day; LOAEL= 20 mg/kg/day 

based on decreased percentage of pup born 
Quizalofop-P-ethyl Human Health Risk Assessment DP No. 384660 and 386678

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Table A.2.2 Subchronic, Chronic and Other Toxicities Profile for Quizalofop ethyl.

Guideline No./ 

Study Type/

MRID Nos.

Doses/Classification

Results 1

alive.

Offspring:

NOAEL=5 mg/kg/day; LOAEL= 20 mg/kg/day 

based on decreased pup weights.

870.4200a

Chronic Toxicity/ 

Carcinogenicity

-Rat

00146682 (1985)

(0, 25, 100, 400 ppm)

0, 0.9, 3.7, 15.5 mg/kg/day (M)

0, 1.1, 4.6, 18.6 mg/kg/day (F)

Acceptable/guideline

NOAEL= 0.9/1.1 mg/kg/day (M/F), LOAEL= 

3.7/4.6 mg/kg/day based on increased incidence 

of centrilobular enlargement of the liver in both 

sexes and mild anemia in males. 

Increased incidence, with dose-related trend, of 

hepatocellular carcinomas in females only.

Cancer classification: Category D (not 

classifiable as to human carcinogenicity) 

870.4100b

Chronic toxicity

- dog

00146683(1985)/40242501 

(1987)

(0, 25, 100, 400 ppm)

0, 0.625, 2.5, 10 mg/kg/day (M/F)

(by a standard conversion factor)

Acceptable/Guideline

NOAEL=10 mg/kg/day (HDT).

870.4200b

Carcinogenicity 

- mouse

00146684 (1985)

(0, 2, 10, 20, 80, 320 ppm)

0, 0.3, 1.4, 11.4, 45.7 mg/kg/day 

(by a standard conversion factor)

Acceptable/Guideline

NOAEL=1.4 mg/kg/day; LOAEL=11.4 

mg/kg/day based on increased incidence of 

bilateral testicular atrophy, enlarged liver and 

histopathology finding indicative of 

hepatotoxicity in the liver.

Increased incidences of ovarian tumors in 

females and liver tumors in males at the highdose.

Cancer classification: Category D (not 

classifiable as to human carcinogenicity)

870.7485

Metabolism

See metabolism section for 

details.

Acceptable/Guideline

See metabolism section for details.

870,7800. 

Immunotoxicity 

screen. 

48500401(2011)

0, 10, 100, 300, or 600 ppm (0, 2, 

20, 55, or 103 mg/kg/day.

Acceptable/Guideline.

No evidence of immunotoxicity. 

1. LOAEL = Lowest observed adverse effect level, NOAEL = No observed adverse effect level. 

2

. GD = Gestation Day

3. NZW = New Zealand White Rabbits