EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR 

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division Contact: Reuben Baris, 703-305-7356

Nissan Chemical Industries, Ltd.

5F8367

EPA has received a pesticide petition (5F8367) from Nissan Chemical Industries, 

Ltd., 3-Chome, Kanda-Nishiki-Cho Chiyoda-Ku, Tokyo 101-0054 Japan requesting, 

pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 

U.S.C. 346a(d), to amend 40 CFR part 180.441 by establishing tolerances for residues of

quizalofop-P-ethyl ester, [ethyl(R)-(2-[4-((6-chloroquinoxalin-2-

yl)oxy)phenoxy)propanoate], and its acid metabolite quizalofop-P, [R-(2-(4-((6-

quinoxalin-2-yl)oxy)phenoxy)propanoic acid and the S enantiomers of both the ester and 

the acid, all expressed as quizalofop-P-ethyl ester in or on the raw agricultural 

commodities Rice at 0.05 parts per million (ppm) and Crayfish at 0.04 ppm. EPA has 

determined that the petition contains data or information regarding the elements set forth 

in section 408(d)(2) of FFDCA; however, EPA has not fully evaluated the sufficiency of 

the submitted data at this time or whether the data supports granting of the petition. 

Additional data may be needed before EPA rules on the petition.

A. Residue Chemistry

1. Plant metabolism. Plant metabolism studies have been conducted for soybeans,

cotton, tomatoes, potatoes, and sugar beets. These studies have been previously reviewed 

and accepted by EPA (see PP3F4268 and PP0F6076). 

In addition, a rice metabolism study was initiated to investigate the metabolism of 

quizalofop-P-ethyl in herbicide-tolerant rice. Two labels were tested ([hydroquinone -U- 14C]-quizalofop and [quinoxaline-phenyl-U14C]-quizalofop at a nominal application of 

100 g ai/ha at BBCH 13-14 followed by 140 g ai/ha at Panicle Initiation (~BBCH 30). 

Quizalofop-P-ethyl was extensively metabolized and only two metabolites were observed 

higher than 5% TRR, CQO and Quizalofop-P. As 14C-residues in the grain were low, the 

radioactivity in grain samples was only determined by TRR. The rice metabolism study 

supports the known plant metabolism of Quizalofop-P-ethyl and does not indicate a 

difference in metabolism due to the herbicide tolerant nature of the rice.

In summary, quizalofop-P-ethyl ester is metabolized by cleavage at three sites as follows.

1. Hydrolysis of the ethyl ester to form the quizalofop-P acid (primary pathway).

2. Cleavage of the enol ether linkage in the acid, between the phenyl and 

quinoxalinyl rings, to form phenols.

3. Cleavage of the ether linkage between the propanic group and the phenyl ring to 

form a phenol.
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The plant metabolism data show that the quizalofop-P-ethyl ester itself does not 

translocate, but is rapidly hydrolyzed to the corresponding acid. The phenols conjugate 

with the plant sugars. Metabolism studies in soybeans using the racemic mixture 

quizalofop ethyl ester and the resolved D+ isomer show nearly identical pathways. 

The nature of the quizalofop-P-ethyl ester residue in cottonseed, potatoes, 

tomatoes, soybeans, sugar beets, sunflower seeds, wheat, barley, and rice is adequately 

understood. The residues of concern are quizalofop-P-ethyl ester and its acid metabolite, 

quizalofop-P, and the S enantiomers of both the ester and the acid, all expressed as 

quizalofop-P-ethyl ester.

2. Analytical method. The Analytical Method Number Meth-147 was originally 

developed and validated for the determination of residues of quizalofop-P-ethyl (QPE) as 

2-methoxy-6-chloroquinoxaline (MeCHQ) in wheat, barley and alfalfa raw agricultural 

commodities and wheat grain processed commodities at Morse Laboratories, Inc, (Morse 

Laboratories, Inc. Analytical Method No. Meth-147. January 10, 2002; MRID 

44967703). This method included the methanolysis to convert the residues of all possible 

metabolites to a common moiety analyte, 2-methoxy-6-chloroquinoxaline (MeCHQ) 

followed by several sample clean-up steps. The final determination of residues was 

performed using reverse-phase HPLC with fluorescence detection. This method was 

further modified using) as 2-methoxy-6-chloroquinoxaline (MeCHQ) for the analysis of 

rice commodities at the limit of quantitation (LOQ) of 0.05 mg/kg. The modifications 

were used only in the sample clean-up and final determination steps for data collection 

purpose. A brief description of the modified method is provided below.

The method involves refluxing samples with methanolic potassium hydroxide to 

convert quizalofop-P-ethyl and quizalofop-P residues to a common analyte, 2-methoxy-6-

chloroquinoxaline (MeCHQ). The resulting extract are then centrifuged, diluted with 

methanol, and analyzed by LC-MS/MS with the positive ionization mode monitoring ion 

transition m/z 195→167 for MeCHQ. Quantitation is obtained using an external 

calibration curve of standard for MeCHQ. The residues are expressed in terms of the 

parent compound, QPE, using a molecular weight conversion factor. The limit of 

quantitation (LOQ) is 0.05 mg/kg based on the lowest level of method validation. 

The independent lab validation (ILV) of the modified method for rice analysis is 

not conducted as this is used only for the data collection of rice commodities and is not to 

be used for enforcement purposes.

4. Magnitude of residues.

Magnitude of the Residue – Rice Crop Field Trials 

A total of 17 trials on rice conducted during the 2013 and 2014 growing seasons 

in NAFTA Regions 4 (AR, five trials; LA, six trials; MO, one trial), 5 (MO, one trial), 6 

(TX, two trials), and 10 (CA, two trials) reflecting two broadcast, early-season 

applications of quizalofop-P-ethyl (105 g/L EC) , the first targeting 100 g ai/ha (BBCH 

13-14, 3-4 leaves unfolded), and a second targeting 140 g ai/ha, with a 28-day 
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retreatment interval (240 g ai/ha/season). Total quizalofop-P-ethyl residues, determined 

as MeCHQ and expressed as parent equivalents, were <0.05 ppm in treated grain samples 

(and <0.05-0.194 ppm in treated straw samples, each harvested at normal maturity, 69-95 

days after the last (second) application. Total quizalofop-P-ethyl residues, determined as 

MeCHQ and expressed as parent equivalents, were <0.05 ppm in treated grain samples 

(and <0.05-0.194 ppm in treated straw samples, each harvested at normal maturity, 69-95 

days after the last (second) application.

At eight of the trials described above (for the2013 growing season only), an 

additional treated plot (Treatment 3, side-by-side plots) was included reflecting two 

broadcast, early-season applications of quizalofop-P-ethyl (105 g/L EC) , the first 

targeting 100 g ai/ha (BBCH 11-12, 1-2 leaves unfolded), and a second targeting 140 g 

ai/ha, with a 14-day retreatment interval (240 g ai/ha/season). Total quizalofop residues, 

determined as MeCHQ and expressed as parent equivalents, were <0.05 ppm in 12 

treated grain samples and <0.05-0.067 ppm in 12 treated straw samples, each harvested at 

normal maturity, 97-109 days after the last (second) application. Total quizalofop 

residues, determined as MeCHQ and expressed as parent equivalents, were <0.05 ppm in 

12 treated grain samples and <0.05-0.067 ppm in 12 treated straw samples, each 

harvested at normal maturity, 97-109 days after the last (second) application. 

Samples of seeds (including hulls) were analyzed for residues of quizalofop-Pethyl and quizalofop-P, expressed as quizalofop-P-ethyl, using method meth-147.

The overall recoveries in grain and straw were at 0.05 and 5.0 ppm were 73-117% 

(84±13%, n=16) and 71-108% (84±16%, n=14).

The rice RAC samples were stored frozen for a maximum of 154 days (5.1 

months) for grain and 161 days (5.3 months) for straw, from collection to analysis for 

residues of quizalofop-P-ethyl. The available storage stability data demonstrate that 

residues of quizalofop-P-ethyl and quizalofop-P are stable stored frozen in wheat grain 

for at least 12 months. These data support the storage intervals and conditions incurred 

by the residue samples in this study.

Magnitude of the Residue – Rice Processing Studies

A processing study was conducted using rice grown in NAFTA Regions 4 (MO, 

one trial) and 6 (TX, one trial). The rice RAC samples (grain) were harvested at normal 

maturity, 90 days after the last (second) application, and were then processed, The treated 

plot received two broadcast foliar applications of a 105 g/L emulsifiable concentrate (EC) 

formulation of quizalofop-P-ethyl (formulation code, BAS 9152 9 H) targeting 300 + 420 

g ai/ha/application (0.27 + 0.37 lb ai/A), with a retreatment interval targeting 28 days, for 

a total rate of 720 g ai/ha (0.64 lb ai/A/season). The first spray made at the 4 leaf growth 

stage (BBCH 14) for rice. The actual rates were 294-305 g ai/ha (1st application) and 

414-417 g ai/ha (2nd application), at a 28-day RTI, resulting in a total exaggerated rate of 

708-722 g ai/ha (0.631-0.644 lb ai/A/season). 
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The rice RAC and processed commodity samples were analyzed using a validated 

method Meth-147 (MRID 44967703). The limit of quantitation of the analytical method 

is 0.05 ppm. The overall recoveries in grain and straw were at 0.05 and 5.0 ppm were 73-

117% (84±13%, n=16) and 71-108% (84±16%, n=14).

A comparison of the residues in the RAC with those in each processed fraction 

indicated that total quizalofop residues do not concentrate in the processed fractions of 

rice: Total quizalofop residues, determined as MeCHQ and expressed as parent 

equivalents, were non-quantifiable (<0.05 ppm) in all rice processed commodity samples 

collected during the study.

Magnitude of the Residue in Animals. 

A ruminant feeding study has been submitted and reviewed by EPA. In summary, 

three groups of three lactating dairy cows (plus a control group) were fed 0.1, 0.5, and 5.0 

ppm quizalofop-ethyl (encapsulated) for 28 consecutive days. Milk was collected daily 

and a sub-sample was divided into skim milk and cream. Two cows were sacrificed after 

28 days with samples of fat, skeletal muscle, liver, and kidney being collected and 

analyzed. The remaining cow in each test group was fed a regular diet without 

encapsulated quizalofop-ethyl for 7 additional days before sacrifice. Whole milk, skim 

milk, and cream from the control, and the 0.1 and 0.5 ppm dose groups showed no 

quizalofop to < 0.02 ppm (0.05 ppm in cream). From the 5 ppm dose, quizalofop residues 

ranged from 0.01 to 0.02 ppm in whole, and when these samples were separated into 

cream and skim milk, the quizalofop partitioned into the cream with residues plateauing 

at 0.26 to 0.31 ppm. No quizalofop to < 0.02 ppm was detected in skeletal muscle, and to 

< 0.05 ppm was detected in any liver or fat sample from any of the three doses. 

Quizalofop was detected in one kidney sample as 0.05 ppm from the 5 ppm dose.

From the feed items in this petition, all of the feed items in cattle diets can be 

treated with quizalofop-ethyl. A theoretical beef cattle diet consisting of canola meal, 

bean and pea forage, pea hay, and sugar beet tops which none-the-less maximizes the 

potential quizalofop exposure of 2.1 ppm. A theoretical dairy cattle diet consisting of pea 

and bean forage would none-the-less maximize the potential quizalofop exposure at 2.4 

ppm. Substitutions of other feed items and varying their percentages in the diets would 

give a lower dietary quizalofop burden.

The results of the quizalofop-ethyl bovine feeding study show that finite residues 

will actually occur in milk and tissues from the feeding of quizalofop-ethyl treated RACS 

or their processed feed items when Assure® II is used as directed. The established 

quizalofop and quizalofop-ethyl tolerance in milk, and in fat, meat, and meat by-products 

of cattle, goats, hogs, horse, and sheep are adequate and need not be increased from these 

additional uses.

A poultry feeding study has been submitted and reviewed. In summary, 3 groups 

of 20 hens (plus 1 control group) were dosed with encapsulated quizalofop ethyl ester at 

0.1, 0.5, and 5 ppm daily for 28 consecutive days. Eggs were collected daily, and after 28 
5

days 3/4 of the hens in each test group were sacrificed, and samples of fat, liver, kidney, 

breast and thigh muscles were collected and analyzed. Tissues from each test group were 

pooled prior to analysis. The remaining five hens were fed a regular poultry diet without 

quizalofop-ethyl for an additional 7 days before sacrifice. No quizalofop residues were 

detected in the liver to < 0.05 ppm, and in breast and thigh muscles to < 0.02 ppm for any 

dose administered. From the 5 ppm dose, one kidney sample showed 0.09 ppm 

quizalofop, two fat samples were 0.05 and 0.06 ppm quizalofop, and one egg sample was 

0.02 ppm quizalofop.

The results of the quizalofop-ethyl poultry feeding study show that while it is not 

possible to establish with certainty whether finite residues will actually occur in eggs and 

tissues from the feeding of quizalofop-ethyl treated RACS or their processed feed items 

when Assure® II is used as directed, there is a reasonable expectation for such residues to 

occur. The established tolerance of quizalofop and quizalofop-ethyl in eggs, and in fat, 

meat, and meat by-products of poultry are adequate and need not be changed for these 

additional uses.

Magnitude of the Residue in Animals - Crayfish 

A field accumulation study in crayfish was performed to test for possible 

accumulation of quizalofop-P-ethyl in crayfish tissues. The residues (Quizalofop-P) in 

water reached as high as 0.0487 mg/L on Day 0 and had decreased to 0.0252 mg/L by 

Day 28. Parent residues were not detectable in water. In edible crayfish tissue, residues 

of quizalofop-P were measured at 0.024 mg/kg on Day 1- 0.017 mg/kg on Day 14, and 

were below LOQ (0.01 mg/kg) on Days 21 and 28. Parent was not detectable any edible 

tissues. As a conservative estimate, an MRL of 0.04 mg/kg is proposed crayfish. The 

value of 0.04 mg/kg was used as part of the dietary risk calculations below.

B. Toxicological Profile

1. Acute toxicity. Several acute toxicology studies were conducted, and the 

overall results placed technical grade quizalofop-ethyl in toxicity Category III. These 

include the following studies in Category III: acute oral toxicity (LD50s 1480 and 1670 

for female and male rats, respectively) and eye irritation (mild effects; reversible within 4 

days). Dermal toxicity (LD50 > 5,000 mg/kg; rabbit), inhalation toxicity (LC50 > 5.8 

mg/L; rat) and dermal irritation were classified within Category IV. Technical 

quizalofop ethyl was not a dermal sensitizer.

2. Genotoxicty. Technical quizalofop-ethyl was negative in the following 

genotoxicity tests: bacterial gene mutation assays with E. coli and S. typhimurium; gene 

mutation assays in Chinese hamster ovary(CHO) cells ; in vitro DNA damage assays with 

B. subtillis and in rat hepatocytes; and an in vitro chromosomal aberration test in CHO 

cells.

3. Reproductive and developmental toxicity. A developmental toxicity study in 

rats administered dosage levels of 0, 30, 100, and 300 mg/kg/day. The maternal toxicity 
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no-observed effect level (NOEL) was 30 mg/kg/day and a developmental toxicity NOEL 

was greater than the highest dose tested (HDT) of 300 mg/kg/day. The maternal NOEL 

was based on reduced food consumption and increased liver weights. A developmental 

toxicity study in rats administered dosage levels of 0, 30, 100, and 300 mg/kg/day. The 

maternal toxicity no-observed effect level (NOEL) was 30 mg/kg/day and a 

developmental toxicity NOEL was greater than the highest dose tested (HDT) of 300 

mg/kg/day. The maternal NOEL was based on reduced food consumption and increased 

liver weights.

A developmental toxicity study in rabbits administered dosage levels of 0, 7, 20, 

and 60 mg/kg/day with no developmental effects noted at 60 mg/kg/day (HDT). The 

maternal toxicity NOEL was 20 mg/kg/day based on decreases in food consumption and 

body weight gain at 60/mg/kg/day (HDT). 

A two-generation reproduction study in rats fed diets containing 0, 25, 100 or 400 

ppm (or approximately 0, 1.25, 5, and 20 mg/kg/day, respectively) with a developmental 

(systemic effects) NOEL of 1.25 mg/kg/day for F2B weanlings based on increased liver 

weights and increased incidence of eosinophilic changes in the livers at 5.0 mg/kg/day. 

These liver changes were considered to be physiological or adaptive changes to 

compound exposure among weanlings. When access to the mother’s feed is available, it 

is a common observation that young rats will begin consuming chow prior to complete 

weaning at 21 days of age. Consumption could not be quantified; therefore, the maternal 

consumption was assumed as the NOEL. If normalized on a body weight basis, 

exposures to the weanling rats were likely higher. The parental NOEL of 5.0 mg/kg/day 

was based on decreased body weight and premating weight gain in males at 20 

mg/kg/day (HDT)

4. Subchronic toxicity. A 90-day study was conducted in rats fed diets containing 

0, 40, 128, and 1,280 ppm (or approximately 0, 2, 6.4, and 64 mg/kg/day, respectively). 

The NOEL was 2 mg/kg/day, based on increased liver weights at 6.4 mg/kg.

A 90-day feeding study in mice was conducted with diets that contained 0, 100, 

316 or 1,000 ppm (or approximately 0, 15, 47.4, and 150 mg/kg/day, respectively). The 

NOEL was <15 mg/kg/day, the lowest dose tested (LDT), based on increased liver 

weights and reversible histopathological effects in the liver at the LDT.

A 6-month feeding study in dogs was conducted with diets that contained 0, 25, 

100, or 400 ppm (or approximately 0, 0.625, 2.5, and 10 mg/kg/day, respectively). The 

NOEL was 2.5 mg/kg/day based on increased blood urea nitrogen at 10 mg/kg/day.

A 21-day dermal study was conducted in rabbits at doses of 0, 125, 500, or 2,000 

mg/kg/day. The NOEL was 2,000 mg/kg/day (HDT).

5. Chronic toxicity. An 18-month carcinogenicity study was conducted in CD-1 

mice fed diets containing 0, 2, 10, 80, or 320 ppm (or approximately 0, 0.3, 1.5, 12, or 48 

mg/kg/day, respectively). No carcinogenic effects were observed under the conditions of 

the study at levels up to and including 12 mg/kg/day. A marginal increase in the 
7

incidence of hepatocellular tumors was observed at 48 mg/kg/day, the HDT, which 

exceeded the maximum tolerated dose (MTD). (See the discussion by the EPA 

Carcinogenicity Peer Review Committee. Toxicology Branch Peer Review Committee: 

Draft Document on Assure based on November 5, 1986 CPRC Meeting Dated December 

9, 1986).

A two-year chronic toxicity/carcinogenicity study was conducted in rats fed diets 

containing 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). No carcinogenic effects were observed 

under the conditions of the study at levels up to and including 18.6 g/kg/day (HDT). The 

systemic NOEL was 0.9 mg/kg/day based on altered red cell parameters and 

slight/minimal centrilobuler enlargement of the liver at 3.7 mg/kg/day.

A one-year feeding study was conducted in dogs fed diets containing 0, 25, 100, 

or 400 ppm (or approximately 0, 0.625, 2.5, or 10 mg/kg/day, respectively). The NOEL 

was 10 mg/kg/day (HDT).

The Carcinogenicity Peer Review Committee (CPRC) of HED has evaluated the 

rat and mouse cancer studies on quizalofop along with other relevant short-term toxicity 

studies, mutagenicity studies, and structure activity relationships. The CPRC concluded, 

after three meetings and an evaluation by the EPA Science Advisory Panel (SAP), that 

the classification should be a Category D (not classifiable as to human cancer potential). 

No new cancer studies were required. (CPRC Report: Peer Review of Assure, February 

6, 1987; JA Quest to RJ Taylor. SAP Findings (Assure) Document signed by Steve 

Johnson, December 23, 1987).

The first CPRC review tentatively concluded that quizalofop should be classified 

as a Category B2 (probable human carcinogen). That classification was based on liver 

tumors in female rats, ovarian tumors in female mice, and liver tumors in male mice. 

This classification was downgraded to a Category C (possible human carcinogen) at a 

second CPRC review. The change in classification resulted from a reexamination of the 

liver tumors in female rats and ovarian tumors in female mice. The first peer review had 

found a statistically significant positive trend for liver carcinomas in female rats. 

Subsequent to this conclusion, a tumor data reevaluation showed a reduced number of 

carcinomas. Although there remained a statistically significant positive trend for 

carcinomas in the study, the CPRC concluded that the carcinomas were not biologically 

significant given the few carcinomas identified (one at the mid-dose and two at the high 

dose). Noting that this level of carcinomas was within historical levels, the CPRC 

concluded that administration of quizalofop did not appear to be associated with the liver 

carcinomas.

The CPRC had first attached importance to the fact that the ovarian tumors in 

female mice, were statistically significant at the high dose compared to historical control 

values, and statistically significant when compared to concurrent controls. However, 

review of further historical control data showed that the level of ovarian tumors in the 

quizalofop study was similar to the background rate in several other studies. Given this 
8

information and the fact that the quizalofop study showed no hyperplasia of the ovary, no 

signs of endocrine activity related to ovarian function, and no dose response relationship, 

the CPRC concluded that the ovarian tumors were probably not compound-related.

The findings of the second CPRC review were presented to the SAP. The SAP 

concurred with the CPRC conclusion that the liver tumors in female rats and the ovary 

tumors in female mice showed no evidence of carcinogenicity. However, the SAP 

disagreed with CPRC’s classification of quizalofop as a Category C based on the liver 

tumors in male mice. The SAP concluded that the mouse liver tumors did not support 

such a classification because the tumors occurred at a dose above the MTD and because 

they were not statistically significant if they had a “p” value of less than 0.05. The SAP 

believed that such greater statistical rigor was appropriate for variable tumor endpoints 

such as male mouse liver tumors.

Following the SAP review, the CPRC changed the classification for quizalofop to 

Category D. The Category D classification is based on an approximate doubling in the 

incidence of male mice liver tumors between controls and the high dose. This finding 

was not considered strong enough to warrant the finding of a Category C (possible human 

carcinogen), since the increase was of marginal statistical significance, occurred at a high 

dose that exceeded the predicted MTD, and occurred in a study in which the concurrent 

control for liver tumors was somewhat low compared to the historical controls; while the 

high dose group was at the upper end of previous historical control groups.

EPA has found the evidence on the carcinogenicity of quizalofop-P-ethyl in 

animals to be equivocal and, therefore, concludes that quizalofop-P-ethyl does not induce 

cancer in animals. 

Important to this conclusion was the following evidence: 

(1) The only statistically significant tumor response that appears compound-related 

was seen at a single dose in a single sex in a single species;

(2) the response was only marginally statistically significant; 

(3) the response was only significant when benign and malignant tumors were 

combined; 

(4) the tumors were in the male mouse liver; 

(5) the tumors were within historical controls; and 

(6) the mutagenicity studies were negative. 

In some circumstances, a finding of animal carcinogenicity would be made 

despite any one, or even several, of the six factors noted. However, the combination of 

all of these factors casts sufficient doubt on the reproducibility of the response in the high 

dose male mouse and therefore, EPA concluded that the evidence on carcinogenicity is 

equivocal.

6. Animal metabolism. Animal metabolism studies have been conducted with 

laying hens and lactating goats using 14C-phenyl and 14C-quinoxaline quizalofop-ethyl. 
9

These studies were reviewed and accepted by EPA. EPA concluded that the metabolism 

of quizalofop-P-ethyl is adequately understood. 

The primary metabolic pathway in ruminants is via hydrolysis of the ethyl ester to 

form the quizalofop--methyl. In poultry, the primary metabolic pathway is also the 

hydrolysis of the ethyl ester to form the quizalofop acid, followed by the methyl 

esterification to form the quizalofop-methyl as a minor pathway of metabolism. The 

residues of concern are quizalofop-ethyl, quizalofop-methyl, and quizalofop, all 

expressed as quizalofop-ethyl. There is no evidence that the metabolites of quizalofopethyl, as identified in animal metabolism studies, have any toxicological significance.

7. Metabolite toxicology. There is no evidence that the metabolites of quizalofopethyl as identified as either the plant or animal metabolism studies are of any 

toxicological significance.

8. Endocrine disruption. No special studies investigating potential estrogenic or 

other endocrine effects of quizalofop-P-ethyl have been conducted. However, the 

standard battery of required toxicology studies has been completed. These include an 

evaluation of the potential effects on reproduction and development, and an evaluation of 

the pathology of the endocrine organs following repeated or long-term exposure to doses 

that far exceed likely human exposures. Based on these studies there is no evidence to 

suggest that quizalofop-P-ethyl has an adverse effect on the endocrine system.

C. Aggregate Exposure

1. Dietary exposure. A chronic dietary exposure and risk assessment was

conducted for quizalofop-P-ethyl using the Dietary Exposure Evaluation Model (DEEM) 

and the USDA Continuing Survey of Food Intake by Individuals (CSFII, for 2005-2010, 

as contained in DEEM Ver 4.02). An acute dietary exposure and risk assessment is not 

required because the US EPA has determined that there are no effects observed in oral 

toxicity studies that could be attributed to a single-dose exposure from quizalofop-Pethyl. The chronic dietary exposure assessment was conducted using 100% crop 

treatment factors, tolerance level residues for all currently approved tolerances for 

quizalofop-ethyl (40 CFR 180.441) and the proposed new tolerances for rice at 0.05 ppm 

and crayfish at 0.04 ppm. The chronic dietary exposure included drinking water at 11.5 

ppb. 

A. Acute Dietary Exposure. An acute risk assessment is not required because the

US EPA has determined that there are no effects observed in oral toxicity studies that 

could be attributed to a single-dose exposure from quizalofop-P-ethyl.

B. Chronic Dietary Exposure. The calculated chronic dietary exposures (food + 

drinking water) for all populations are shown in Table 1. The highest exposure 

population sub-group was infants (< 1 year old) and utilized 34.6 % cPAD. The results 

of the risk assessment show that for all populations the exposures are below a level of 

concern (< 100% cPAD). Additional refinements in the dietary risk assessment (i.e. 

utilizing anticipated residue values, percent crop treated values) would further reduce the 
10

estimated exposure values and utilized % cPAD. 

Table 1. Results for Quizalofop-P-ethyl Chronic Dietary Exposure (Food and 

Water) Considering All Commodities using DEEM-FCID

Population Exposure Estimate % cPAD

Subgroups (mg/kg b.w./day)

U.S. Population 0.001179 13.1

All Infants (< 1 year old) 0.003118 34.6

Children (1-2 years old) 0.003052 33.9

Children (3-5 years old) 0.002514 27.9

Children (6-12 years old) 0.001675 18.6

Youth (13-19 years old) 0.001073 11.9

Adults (20-49 years old) 0.000983 10.9

Adults (50+ years old) 0.000885 9.8

Females (13-49 years old) 0.000967 10.0

Chronic Aggregate Exposure and Risk: 

The chronic aggregate exposure includes food and drinking water. Therefore, the

chronic dietary exposure for food and drinking water represents the chronic aggregate 

exposure. A short-term and intermediate term aggregate exposure assessment includes 

food, drinking water, and residential exposure. Quizalofop-P-ethyl does not have any

uses that would result in residential exposure. Therefore, the short-term and 

intermediate-term aggregate exposure assessment is not required. 

i. Food. Not applicable as food and drinking water are included in the assessment 

above.

ii. Drinking water. The rice use for quizalofop-P-ethyl resulted in the highest 

modeled drinking water concentrations. The Tier II Rice model resulted in chronic 

estimated drinking water concentrations of 11.5 ug/L. The drinking water exposures 

were included in the chronic dietary exposure assessment. 

2. Non-dietary exposure. Quizalofop-P-ethyl is not registered for use in residential 

settings.

D. Cumulative Effects

There is no evidence to indicate or suggest that quizalofop-P-ethyl has any toxic 

effects on mammals that would be cumulative with those of any other chemicals.

E. Safety Determination

1. U.S. population. For the U.S. population, the calculated aggregate exposure 
11

from all current uses and the proposed new uses is equivalent to 13.1% of the cPAD. 

Because the calculated aggregate exposures, expressed as percentages of the cPAD, are 

well below 100%, there is reasonable certainty that the current uses and the proposed new 

uses of quizalofop-P-ethyl will not result in an unacceptable risk. 

2. Infants and children. The population subgroup with the highest predicted level 

of chronic exposure was infants (<1 year) subgroup with an exposure of 0.003118 mg/kg 

bw/day. The chronic exposure for all infants (<1 year) is equivalent to 34.6% of the 

cPAD. Because the predicted exposures, expressed as percentages of the cPAD, for all 

existing and new uses are well below 100%, there is reasonable certainty that the current 

uses and proposed new uses for quizalofop-P-ethyl will not result in an unacceptable risk.

F. International Tolerances

There are no Mexican, Canadian or Codex MRL’s/tolerances for rice; therefore, 

compatibility is not an issue.