Quizalofop-ethyl and Quizalofop-P-ethyl 

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HED recommends that the 40 CFR § 180.441 tolerance for residues of quizalofop in sunflower 

seeds be revised from 1.9 ppm to 2.0 ppm to account for increases in residues found in a recent 

sunflower residue chemistry study (MRID 47910507). In addition, based on the revised Table 1 

of Guideline 860.1000, soybean soapstock and sugar beet tops are no longer important 

feedstuffs; therefore, those tolerances should be removed from 40 CFR § 180.441.

Maximum residue limits (MRLs) for quizalofop have not been established by Mexico or Codex.

Canada MRLs and US tolerances for quizalofop are harmonized for some commodities. 

Harmonization is not possible for dry beans, edible podded beans, and milk fat since the US 

tolerances are lower than the Canadian MRLs. For harmonization of sugar beet commodities, 

HED recommends the establishment of a US tolerance for sugar beet at 0.2 ppm and the removal 

of the individual US tolerances for sugar beet roots, sugar beet molasses, and sugar beet tops.

Background

Quizalofop ethyl and quizalofop-P-ethyl are selective herbicides used for the control of annual

and perennial grasses in crops and non-croplands (rights-of-way, fencerows, etc). They can be 

applied using ground boom equipment and by fixed wing aircraft as broadcast and banded 

applications. Quizalofop ethyl is a 50/50 racemic mixture of R- and S-enantiomers. QuizalofopP-ethyl is the purified R-enantiomer, which is the pesticidally active isomer. HED has 

determined that the toxicological profile of the 50/50 racemic mixture (quizalofop ethyl) and the 

R-enantiomer (quizalofop-P-ethyl) are similar, and that the currently available toxicity and 

residue data on quizalofop ethyl are adequate to support risk assessments reflecting uses of either

quizalofop ethyl or quizalofop-P-ethyl. The two compounds are collectively referred to as 

“quizalofop” in this document. 

All of the currently registered products are formulated as the R-enantiomer, quizalofop-P-ethyl. 

Presently, quizalofop-P-ethyl is registered for use on the following food crops: barley, dry beans, 

canola, crambe, cotton, dry and succulent peas, lentils, mint, rapeseed, snap beans, sorghum, 

soybean, sugar beets, flaxseed, sunflower, wheat and pineapple. Quizalofop-P-ethyl is also 

registered on the following nonfood crops grown for seed only: alfalfa, carrots, cabbage, garlic, 

onion, radish, spinach, Swiss chard and rye. There are no residential uses of quizalofop. 

Tolerances are established under 40 CFR §180.441for residues of quizalofop ethyl.

Quizalofop ethyl was first registered in 1988 and quizalofop-P-ethyl was first registered in 1990. 

As a result neither chemical was subject to review under the reregistration process under the 

Federal Insecticide Fungicide and Rodenticide Act (FIFRA) and the Food Quality Protection Act 

(FQPA) for chemicals registered prior to 1984. Consequently, neither a Reregistration Eligibility 

Decision (RED) nor a Tolerance Reregistration Eligibility Decision (TRED) was issued. 

An HED scoping document in support of registration review of quizalofop ethyl and quizalofopP-ethyl was completed in 2007 (Eiden, 2007). A subsequent human health risk assessment was 

performed in 2011 in association with the then-proposed new uses on sorghum and rapeseed and 

is the most recent assessment (11/17/11; D384660 and D386678). No outstanding human health 

data requirements for quizalofop were identified in either document or in the June 2008 final 
Quizalofop-ethyl and Quizalofop-P-ethyl 

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workplan for the registration review of quizalofop 

(http://www.epa.gov/oppsrrd1/registration_review/quizalofop/ index.htm). 

Toxicology/Hazard Assessment

Quizalfop is classified as catagory IV for the acute oral, dermal and inhalation toxicity in the rat. 

It was negative for dermal irritation in the rabbit and a dermal non-sensitizer in the guinea pig. 

The liver is the target organ as evidenced by increased liver weight and histopathological

changes in the liver. A metabolism study in rats indicated 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. 

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 quizalofop ethyl database does not 

indicate it 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 as to human carcinogenicity). Mutagenicity studies conducted on 

quizalofop ethyl did not demonstrate evidence of mutagenic potential. For detailed hazard 

characterizations, refer to the 2011 risk assessment (D384660 and D386678).

No toxicity studies have been received since the last human health risk assessment in 2011. The

Agency has modified the Pesticide Data Requirements for Assessing Toxicity (40 CFR 

§158.500), which now require submission of acute and sub-chronic neurotoxicity testing. The 

HED Hazard and Science Policy Council (HASPOC) recently concluded that, based on a weightof-the-evidence (WOE) approach, acute and sub-chronic neurotoxicity studies are not required at 

this time for quizalofop. This approach included the following considerations: 1) the lack of 

neurotoxicity in the available toxicology studies for quizalofop; 2) liver toxicity is the primary 

toxic effect seen in the quizalofop database and provides the most sensitive point of departure 

(POD) for risk assessment; and 3) the low concern for neurotoxicity in other members of this 

class of chemicals (HASPOC meeting, TXR#: 0056481, October 4, 2012). The waiver for the 

sub-chronic inhalation study was also granted by the HASPOC. This WOE approach considered 

all the available hazard and exposure information for quizalofop, including: (1) the low vapor 

pressure of quizalofop (8.3 x 10-10 mm Hg); (2) the low acute inhalation toxicity of quizalofop 

(Toxicity Category IV); and (3) the use of a conservative oral POD resulting in screening-level 

MOEs for handler exposures ranging from 2,900 to 211,000. 

The risk assessment team has re-evaluated the PODs and uncertainty factors from the most 

recent risk assessment, with respect to anticipated exposure pathways and current policies on 

selecting endpoints and safety factors, including the safety factor for the protection of infants and 

children (FQPA Safety Factor). The point of departure for the chronic dietary scenario is based 

on the lowest NOAEL in the database of 0.9 mg/kg/day from the chronic rat study. A risk 

assessment for the dermal scenario is not required since the 28-day dermal study revealed no 

adverse responses at the limit dose of 2000 mg/kg/day. The acute dietary scenario was not 

evaluated, since no single-dose effects were identified in the oral toxicity database. Inhalation 

scenarios were not assessed since inhalation exposure is not expected. The toxicity database for 

quizalofop is adequate in terms of endpoint selection and dose response information to 

characterize the potential for prenatal or postnatal risk to infants and children. There are no 
Quizalofop-ethyl and Quizalofop-P-ethyl 

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concerns and no residual uncertainties for pre- and postnatal toxicity. The results of the 

immunotoxicity study do not impact endpoint selection or safety factors. The quizalofop ethyl 

database does not indicate it 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. No changes to the 

toxicological endpoints, PODs and FQPA safety factors selected in 2011 are warranted. The 

toxicology profile and endpoint selection table are listed in Appendices B and C.

Residential Exposure and Risk Assessments

Quizalofop is not registered for use in residential settings. A residential exposure assessment is 

not required.

Dietary Exposure and Risk Assessments

Sufficient residue data are available to assess dietary exposure to quizalofop. A chronic dietary 

(food and drinking water) assessment was conducted in association with the most recently 

registered uses of quizalofop (as quizalofop-P-ethyl) on sorghum and the rapeseed crop group 

20A (Tadayon, 2011). An acute dietary risk assessment was not performed, as an acute endpoint 

was not identified in the hazard assessment. Similarly a cancer risk assessment was not 

performed as quizalofop is not classifiable as to human carcinogenicity.

Children (1-2 years old) were found to have the maximum chronic dietary risk estimate at 29% 

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

100% of cPAD. The dietary assessment is considered very conservative as it was conducted

assuming tolerance level residues and 100% crop treated.

Drinking water concentrations used in the assessment were 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 (Wente, 2011). The 

Environmental Fate and Effects Division (EFED) has reviewed the existing estimated drinking 

water concentrations (EDWCs) for quizalofop and has determined that given current policies the 

EDWCs may increase or decrease only slightly (email communication S. Wente to D. Drew 

8/14/12). Dietary risk estimates that would include any slightly revised EDWCs would still be 

considerably below the level of concern. Results of the quizalofop dietary assessment are 

summarized in the table below.

Table 1. Summary of Chronic Dietary Exposure and Risk for Quizalofop-P-ethyl (Food and Drinking Water)

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
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Table 1. Summary of Chronic Dietary Exposure and Risk for Quizalofop-P-ethyl (Food and Drinking Water)

Population Subgroup cPAD (mg/kg/day)

Chronic

Exposure (mg/kg/day) %cPAD

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

Aggregate Exposure and Risk Assessments

Aggregate risk estimates take into account dietary and residential sources of exposure. As there 

are no registered uses of quizalofop that would result in residential exposure, an aggregate 

assessment (food, water and residential) is not performed. Chronic aggregate exposures consist 

of food and water only and are not of concern (Table 1).

Cumulative Exposure and Risk Assessments

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 (quizalofop ethyl or quizalofop-P-ethyl) and any other substances and quizalofop

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 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/.

Occupational Exposure and Risk Assessments

The occupational exposure and risk assessment addresses risks to workers exposed in an 

occupational setting via the dermal and inhalation routes of exposure. However, for quizalofop, 

quantitative dermal and inhalation risk assessments were not conducted, based on the 

combination of low hazard (via dermal and inhalation routes) and exposure potentials and 

because no endpoints or points of departure for dermal or inhalation exposure were identified. 

Quizalofop is not toxic via the dermal route (based on the lack of toxicity following repeat 

dermal exposure and the lack of concern for developmental/reproductive effects which are not 

examined in the dermal study); therefore, no dermal endpoint was identified. Quizalofop is a 

Category IV Inhalation Toxicant indicating low toxicity by the inhalation route, it is not volatile, 

and it has low use rates. All of these factors indicate that use of quizalofop will not lead to 

inhalation exposures of concern. To support this qualitative assessment, HED has at this time, 

estimated risks from inhalation exposures for workers applying and handling quizalofop products 

for a number of high acreage crops using a screening-level analysis. This screening-level 

analysis uses maximum use rates, maximum acreage, baseline PPE, updated SOP ,and the 

chronic oral RfD to estimate inhalation risks. Risk estimates based on inhalation exposures of 

pesticide handlers (mixers, loaders, applicators) for barley, flax, sunflower, wheat, cotton, 

pineapple, and non-crop areas are all below HED’s level concern. The Margins of Exposure 

(MOEs) resulting from this screening assessment range from 2900 to 211,000 and are not of 

concern as they are well above 100 (the level of concern). A 12-hour Restricted Reentry Interval 

(REI) has been established and is reflected on the labels of all registered products.
Quizalofop-ethyl and Quizalofop-P-ethyl 

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Public Health and Incident Reports

Quizalofop incidents were analyzed in 2007 (M. Hawkins, 07/31/2007, D342226). There were 8 

incidents identified in IDS from 1999 to 2007; there were 10 incidents identified in Poison 

Control Center Data from 1993 to 2005; and there were no incidents identified in NIOSH 

SENSOR data from 1998 to 2003. 

Updated incident analyses of the Main and Aggregate Incident Data System (IDS) from January 

1, 2007 to September 20, 2012, and the National Institute of Occupational Safety and Health 

Sentinel Event Notification System for Occupational Risks (NIOSH SENSOR) from 1998 to 

2008 are consistent with the previous analyses. The results are as follows:

From January 1, 2007, to September 20, 2012, there are no incidents reported in 

either Aggregate IDS or Main IDS that involve quizalofop.

From 1998 to 2008, three cases (which were associated with one drift event) were 

identified in SENSOR as being associated with quizalofop. In 2005, a mother and her 

two children were exposed to a product containing quizalofop through drift from a 

neighbor’s application. All three cases were classified as low in severity. Symptoms 

reported for all three cases include headache, upper respiratory pain/irritation, and 

shortness of breath. Additionally, the mother reported having a cough.

Based on the continued low frequency and severity of incident cases reported for quizalofop, 

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

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

analysis will be conducted (update provided via 10/9/12 email communication S. Recore to D. 

Drew).

Residue Chemistry and Tolerance Recommendations

Residue chemistry deficiencies previously identified for quizalofop were recently evaluated 

along with a recent residue data submission (sunflower residue decline; MRID 47910507) 

(D371923, Negrón-Encarnación, 2012). The deficiencies are resolved with the exception of the 

following: Recovery data are required for the metabolites quizalofop acid and quizalofop methyl 

by using the multiresidue method (860.1360); Storage stability data for quizalofop p-ethyl and 

quizalofop acid in/on field corn and processed commodities are required (860.1380); Based on 

the revised version of Table 1 of OPPTS 860.1000 (June 2008), processing studies (860.1520) 

are required for cotton, meal; cotton, hulls; cotton gin byproducts; and cotton, refined oil in order 

to determine if separate tolerances are needed for these processed commodities of cotton; A 

reference standard of 2-methoxy-6-chloroquinoxaline should be sent to the analytical standard 

repository (860.1650). In addition, the livestock grazing restriction on the label for Assure II 

(EPA Reg. No. 352-541) is impractical and should be removed.

Tolerance Recommendations

The submitted residue decline data for sunflower are adequate to satisfy the previous condition 

of registration. Residues slightly increased over the sampling period. A revised tolerance using 

OECD (Organization for Economic Co-operation and Development) calculation procedures is 
Quizalofop-ethyl and Quizalofop-P-ethyl 

Human Health Risk Assessment DP#394192

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proposed to account for this increase. In addition, based on the revised Table 1 of Guideline 

860.1000, soybean soapstock and sugar beet tops are no longer important feedstuffs; therefore,

those tolerances should be eliminated from the 40 CFR § 180.441. HED recommends that 40 

CFR § 180.441 be amended by establishing/removing tolerances for the plant commodities as 

listed in Table 2 below.

International Harmonization

The international residue limits table is included in Appendix D. Maximum residue limits for 

quizalofop have not been established by Mexico or Codex. The Canada and US residue 

definitions for quizalofop ethyl in plants are similar but not identical; however, both reflect 

expression of residues as quizalofop ethyl equivalents and the residues of concern, quizalofop 

ethyl and quizalofop acid, are accounted for either directly or indirectly. 

The Canadian Pest Management Regulatory Agency (PMRA) established MRLs for dry beans, 

edible podded beans, sugar beets, flax, and lentils. Harmonization is not possible for dry beans 

and edible podded beans since the US tolerance is lower than the Canadian MRL. For 

harmonization of sugar beet commodities, HED recommends the establishment of a US tolerance 

for sugar beet at 0.2 ppm and to remove the individual US tolerances for sugar beet roots, sugar 

beet molasses, and sugar beet tops (no longer a significant feedstuff item) (see Table 2 below). 

The US tolerance and Canadian MRL for flax and lentils is equivalent.

The US tolerances and Canadian MRLs values are the identical for all livestock commodities 

except milk fat. The US tolerance expression for livestock commodities is based on residues 

convertible to quizalofop which includes quizalofop ethyl and quizalofop-methyl. Although the 

Canadian tolerance expression doesn’t include quizalofop-methyl, upon communication with the 

PMRA it was noted that the data acquisition methods were the same. Based on this the Canadian 

MRLs and US tolerances for fat, meat, and meat by products of goat, cattle, hog, horse, poultry 

and sheep; eggs; and milk are harmonized. The Canadian MRL for milk fat is lower than the US 

tolerance; therefore, these values cannot be harmonized.

Table 2. Tolerance Summary for Quizalofop (40 CFR § 180.441)

Commodity Current

Tolerance 

(ppm)

HEDRecommended 

Tolerance (ppm)

Comments (correct commodity 

definition)

Soybean, soapstock 1.0 Remove Not a feedstuff item

Sunflower, seed 1.9 2

Beet, sugar - 0.2

Beet, sugar, molasses 0.2 Remove Replace with 0.2 ppm tolerance for 

beet, sugar 

Beet, sugar, roots

0.1

Remove Replace with 0.2 ppm tolerance for 

beet, sugar (Harmonize with 

Canada)

Beet, sugar, tops 0.5 Remove Not a feedstuff item
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Data Requirements

Toxicology

There are no outstanding data requirements.

Residue Chemistry

The following residue chemistry data remain outstanding. See D371923 for details on residue 

chemistry data requirements:

860.1200 Directions for Use

The Section (3) label of Assure II (EPA Reg. No. 352-541) indicates that grazing of livestock 

is prohibited in treated areas. This restriction is not considered practical. Based on the most 

recent version of the label (dated 04/12/2012), this restriction has not yet been removed.

860.1360 Multiresidue Methods

Multiresidue method data (recovery data) for the metabolites, quizalofop acid and 

quizalofop-methyl remain outstanding.

860.1380 Storage Stability

Storage stability data for quizalofop-P-ethyl and quizalofop acid in/on field corn and 

processed commodities have not been received. The available wheat storage stability data 

were tentatively considered adequate to support submitted crop field trial on corn. However, 

when the storage stability study on corn is submitted, the adequacy of the storage stability 

data will be re-evaluated.

860.1520 Processed Food and Feed

Studies to determine the residues in/on cotton, meal; cotton, hulls; cotton gin byproducts; and 

cotton, refined oil are required to determine if separate tolerances are needed for these 

food/feed items.

860.1650 Submittal of Analytical Reference Standards

A reference standard of 2-methoxy-6-chloroquinoxaline should be sent to the analytical 

standard repository.

Occupational Residential Exposure

There are no outstanding data requirements.
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Reference Memoranda

K. Rury, Quizalofop (quizalofop-ethyl and quizalofop-P-ethyl): Summary of Hazard and 

Science Policy Council (HASPOC) Meeting of October 4, 2012 (TXR No.: 0056481)

I. Negrón-Encarnación, 12/4/2012, Quizalofop-P-ethyl. Summary Document to

Support Registration Review and Residue Decline Data for Sunflower in Support of the 

Condition of Registration for Use on Sunflower (PP#0F6076), D371923.

I. Negrón-Encarnación, 11/17/2011, Quizalofop-P-ethyl: Human Health Risk Assessment for 

New Uses on Sorghum, Rapeseed Crop Group 20 A, and Field Corn , D384660 and D386678.

S. Tadayon, 10/25/2011, Quizalofop-P-ethyl. Revised Chronic Dietary Exposure Assessment to 

Support Section 3 Registration for use on Corn, Rapeseed and Sorghum, D395387. 

S.P. Wente, 07/19/2011, Drinking water exposure for quizalofop-P-ethyl in support of 

propagation of herbicide-tolerant field corn and sorghum, D384661.

C. Eiden, 11/7/2007, Quizalofop-ethyl (PC 128711) and Quizalofop-P-ethyl (PC 128709) Health 

Effects Division (HED) Problem Formulation for Registration Review. D342230.

M. Hawkins, 7/31/2007, Review of Quizalofop Incident Reports, D342226.

J. Rowland, 10/24/1997, Quizalofop-ethyl: Report of the Hazard Identification Assessment 

Review Committee (HIARC). TXR 012373.
Quizalofop-ethyl and Quizalofop-P-ethyl 

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Appendix A

Nomenclature and Physicochemical Properties of Quizalofop–P-ethyl

Table A1. Test Compound Nomenclature

Chemical structure

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)

TABLE A2. 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

N

Cl N

O

O

CH3

O

O

CH3
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Appendix B

Toxicology Profile 

B.1 Toxicology Data Requirements

The requirements (40 CFR 158.340) for non food and food uses for quizalofop are below. Use of 

the newguideline 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 (non-rodent)........................................

870.3200 21-Day Dermal ..............................................................

870.3250 90-Day Dermal ..............................................................

870.3465 90-Day Inhalation..........................................................

yes

yes

yes

CR

CR

yes

yes

yes

-

*

870.3700a Developmental Toxicity (rodent)...................................

870.3700b Developmental Toxicity (non-rodent) ...........................

870.3800 Reproduction .................................................................

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent) ..............................................

870.4100b Chronic Toxicity (non-rodent).......................................

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—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

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 Developmental Neurotoxicity.......................................

no

no

yes

yes

CR

-

-

*

*

-

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

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

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

yes

no

yes

yes

yes

yes

* Not required (HASPOC decision, October 4, 2012, TXR#: 0056481)
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B.2 Toxicity Profiles

Table B.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 B.2.2 Sub-chronic, 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 

alive.

Offspring:
Quizalofop-ethyl and Quizalofop-P-ethyl 

Human Health Risk Assessment DP#394192

Page 14 of 19

Table B.2.2 Sub-chronic, Chronic and Other Toxicities Profile for Quizalofop ethyl.

Guideline No./ 

Study Type/

MRID Nos.

Doses/Classification

Results 1

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)

870.5100

Mutagenicity 

Bacterial

00128205

0, 10, 100, 250, 500, 1000, 2500 

μg (+/- S9)

Negative

870.5375

Mutagenicity

Chromosomal 

Aberrations 

(CHO)

00128204

0, 125, 250, 500 & 1000 μg/mL (-

S9)

0, 31.3, 62.5, 125, 250 & 500 

μg/mL (+S9)

Negative

DMN Control: Positive

870.5395

Mutagenicity

Micronucleus 

Assay (Mouse)

00128203

0, 300, 600, 1200 mg/kg/day

Negative

870.5550

MutagenicityUDS

00128202 Negative

870.7485

Metabolism

40328601

Supplementary

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 
Quizalofop-ethyl and Quizalofop-P-ethyl 

Human Health Risk Assessment DP#394192

Page 15 of 19

Table B.2.2 Sub-chronic, Chronic and Other Toxicities Profile for Quizalofop ethyl.

Guideline No./ 

Study Type/

MRID Nos.

Doses/Classification

Results 1

further. 

870.7600 

Dermal 

Penetration

00146679

0.19, 1.9, or 19 mg/rat,

With a10-hour exposure at doses of 0.19, 1.9, 

or 19 mg/rat, the absorption was 8.38, 3.27, and 

2.9% of the applied dose, respectively

870.7800 

Immunotoxicity 

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
Quizalofop-ethyl and Quizalofop-P-ethyl 

Human Health Risk Assessment DP#394192

Page 16 of 19

Appendix C

Table C.1. Summary of Toxicological Points of Departure and Endpoints for Quizalofop 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.
Quizalofop-ethyl and Quizalofop-P-ethyl 

Human Health Risk Assessment DP#394192

Page 17 of 19

Appendix D

International Residue Limits

Quizalofop ethyl (PC Code 128711) and Quizalofop-P-ethyl (PC Code 128709); 09/18/2012

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

40 CFR 180.441:

Plant: quizalofop ethyl residues 

convertible to 2-methoxy-6-

chloroquinoxaline, expressed as the 

stoichiometric equivalent of 

quizalofop ethyl.

ethyl (RS) 2-[4-(6-chloroquinoxalin2-yloxy)phenoxy]

propionate, including the acid 

metabolites of (RS)2-[4-

(6-chloroquinoxalin-2-

yloxy)phenoxy]propanoic acid,

all expressed as quizalofop-ethyl

None

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

US Canada Mexico1 Codex

Barley, grain 0.05

Barley, hay 0.05

Barley, straw 0.05

Bean, dry, seed 0.4 0.15 Dry (adzuki beans, beans, 

blackeyed peas, broad beans, 

kidney beans, lablab beans, lima 

beans, moth beans, mung beans, navy 

beans, pink beans, pinto beans, rice 

beans, tepary beans, urd beans)

0.05 dry chickpeas, lentils, soybeans

Bean, succulent 0.25 0.05 edible podded (jackbeans, moth 

beans, runner beans, snap beans, 

soybeans, sword beans, wax beans, 

yardlong beans)

Beet, sugar, molasses 0.2 0.2 sugar beets2

Beet, sugar, roots 0.1 0.2 sugar beets

Beet, sugar, tops 0.5 0.2 sugar beets

Cotton, undelinted seed 0.1

Cowpea, forage 3.0

Cowpea, hay 3.0

Crambe, meal 2.0

Flax, seed 0.05 0.05 flax

Gold of pleasure, meal 2.0

Lentil, seed 0.05 0.05 lentils

Pea, dry 0.25 0.05 peas

Pea, field, hay 3.0

Pea, field, vines 3.0

Pea, succulent 0.3 0.05 peas

Peppermint, tops 2.0

Rapeseed, meal 2.0
Quizalofop-ethyl and Quizalofop-P-ethyl 

Human Health Risk Assessment DP#394192

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Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

Rapeseed subgroup 20A, 

except flax, seed

1.5 0.05 flax, Oriental mustard seeds 

(condiment type), Oriental mustard 

seeds (oilseed type), rapeseeds 

(canola)

Sorghum, grain, aspirated 

grain fractions

1.0

Sorghum, grain, forage 0.20

Sorghum, grain, grain 0.20

Sorghum, grain, stover 0.30

Soybean, flour 0.5

Soybean, hulls 0.02

Soybean, meal 0.5

Soybean, seed 0.05

Soybean, soapstock 1.0

Spearmint, tops 2.0

Sunflower, seed 1.9

Wheat, forage 0.05

Wheat, grain 0.05

Wheat, hay 0.05

Wheat, straw 0.05

US [40 CFR §180. 441 (a)(2)] Canada Mexico1 Codex

quizalofop ethyl residues 

convertible to quizalofop (2-[4-(6-

chloroquinoxalin-2-yloxy)phenoxy]propanoic acid), 

expressed as quizalofop

Same as above None

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

US Canada Mexico1 Codex

Cattle, fat 0.05 0.05

Cattle, meat 0.02 0.02

Cattle, meat byproducts 0.05 0.05

Egg 0.02 0.02

Goat, fat 0.05 0.05

Goat, meat 0.02 0.02

Goat, meat byproducts 0.05 0.05

Hog, fat 0.05 0.05

Hog, meat 0.02 0.02

Hog, meat byproducts 0.05 0.05

Horse, fat 0.05 0.05

Horse, meat 0.02 0.02

Horse, meat byproducts 0.05 0.05

Milk 0.01 0.01

Milk, fat 0.25 0.05
Quizalofop-ethyl and Quizalofop-P-ethyl 

Human Health Risk Assessment DP#394192

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Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

Poultry, fat 0.05 0.05

Poultry, meat 0.02 0.02

Poultry, meat byproducts 0.05 0.05

Sheep, fat 0.05 0.05

Sheep, meat 0.02 0.02

Sheep, meat byproducts 0.05 0.05

MRLs With No US Equivalent

Rutabaga roots 0.1

Completed: M. Negussie; 09/18/2012

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

2

Included by I. Negron based on electronic communication with PMRA.

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 following table. Compliance with the tolerance levels specified in the following table 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.

Commodity Parts per million

Pineapple 0.1