) 

J 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: 03-DEC-2013 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Quinoxyfen. Human-Health Assessment Scoping Document in Support of 

Registration Review. 

PC Code: 055459 

Decision No.: 481952 

Petition No.: N/ A 

Risk Assessment Type: N/ A 

TXRNo.: N/A 

MRID No.: N/A 

DP Barcode: D414098 

Registration No.: N/ A 

Regulatory Action: Registration Review Scoping Document 

Case No.: 7037 

CAS No.: 124495-18-7 

40 CFR: § 180.588 

George F. Kramer, Ph.D., Senior Che ' ::#• =-3 

Jennifer R. Tyler, Chemist . 

FROM: 

Risk 

Monique 

Assessment 

M. Perron, 

Branch 

S.D., 

1 

Toxicologist 

(RAB 1) 

1'1 

' ..,, 

m"'~/J -6 ~ ~ ~ 

Health Effects Division (HED, 7509P) 

THROUGH: 

RAB1/HED 

Charles W. Smith 

(7509P) 

III, Branch Chief c= ~ 

~ 

~ 

TO: Katherine St. Clair, Chemical Review Manager 

Pesticide Re-Evaluation Division (PRD) (7508P) 

Attached is HED's human-health risk assessment scoping document for quinoxyfen to support 

Registration Review. ' 

Page 1 of23 
Quinoxyfen Registration Review Human-Health Assessment Scoping Document ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ______________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ____________ ______ ______ ______ __

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Executive Summary

Quinoxyfen (5,7-dichloro-4-(4-fluorophenoxy)quinoline) is a fungicide used for protection 

against powdery mildew diseases on a variety of crops. There is currently one end-use product 

(EP) containing quinoxyfen as the active ingredient (ai), a 22.58% ai suspension-concentrate 

(SC) formulation (Quintec®, EPA Reg. No. 62719-375). The most recent human-health risk 

assessment for quinoxyfen was completed in 2013 (Memo, G. Kramer et al., 20-AUG-2013 

D410691) in conjunction with a registration request for use on fruiting vegetables (group 8-10), 

small fruit vine climbing except fuzzy kiwifruit (subgroup 13-07F), and low growing berry 

(subgroup 13-07G). There are no residential or non-agricultural uses registered for quinoxyfen. 

HED has evaluated the status of the human-health assessments for quinoxyfen to determine 

whether sufficient data are available and whether any updates are needed to support Registration 

Review. HED has considered all available data and human-health risk assessments for 

quinoxyfen with respect to its toxicity, exposure, and usage databases, and the most updated 

Agency science policy and risk assessment methodologies to determine the scope of work 

necessary to support Registration Review.

The toxicological database is adequate for Registration Review. The primary target organs 

affected by quinoxyfen are the liver and kidney. The most sensitive species was the rat. Liver 

effects were seen in the subchronic rat and mouse studies as well as the chronic dog study. 

Subchronic effects observed in rats and mice at high doses included increased liver weights, 

hepatocellular hypertrophy, and individual cell hepatocellular necrosis. Chronic effects observed 

in the dog included increased liver weights, increased alkaline phosphatase levels, and increased 

incidence of very slight to slight microscopic hepatic lesions. Kidney effects were only noted in 

the rat combined chronic/carcinogenicity study that resulted in an increased severity of chronic 

progressive glomerulonephropathy in males. Body-weight decrements were noted in the rat 

and/or mouse subchronic, chronic and carcinogenicity studies as well as the rabbit 

developmental and rat reproduction studies. 

Oral rat and rabbit developmental studies showed no increased qualitative or quantitative 

susceptibility of offspring to quinoxyfen in utero. In the rabbit developmental toxicity study, 

maternal and developmental toxicity were observed at the highest dose tested (lowest-observed 

adverse-effect level; LOAEL = 200 mg/kg/day). No maternal or developmental toxicity was 

observed in the rat developmental study up to the limit dose. In the two-generation rat 

reproduction study, no parental effects were observed up to the highest dose tested while firstgeneration pup weights were reduced at the same dose. In isolation, there is evidence of 

quantitative susceptibility in the two-generation reproduction study, but assessments to parental 

animals in this study are intentionally limited to avoid stressing dams and affecting the rearing 

and care of offspring. If additional evaluations had been performed on parental animals in the 

two-generation reproduction study, including histopathology and organ-weight assessments, then 

it is expected that the kidney and liver effects observed in the rat subchronic oral study and in the 

interim (12 months) and final sacrifices of the rat chronic toxicity/carcinogenicity study would 

have been seen at the 100 mg/kg/day dose in the reproduction study. Therefore, when using a 

weight-of-evidence approach that puts the offspring findings in the two-generation reproduction 

toxicity study in context with the full toxicological database there is no concern for susceptibility 

to offspring since it is anticipated that parental toxicity would have been observed at the same 

dose. 
Quinoxyfen Registration Review Human-Health Assessment Scoping Document ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ______________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ____________ ______ ______ ______ __

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Quinoxyfen was categorized as having low acute toxicity via the inhalation, oral, and dermal 

routes (Toxicity Category III or IV). It is a mild eye irritant (Toxicity Category III) and 

classified as a dermal sensitizer, but not a dermal irritant. 

The residue chemistry database is adequate to support current Registration Review requirements. 

Adequate metabolism (crops, livestock, and rotational crops), storage stability, magnitude of the 

residue, and processing data are available to support the registered uses. Adequate methods are 

available for enforcement of the currently established tolerances. 

The dietary-exposure database is adequate to support current registration requirements. The last 

risk assessment provided chronic dietary (food and drinking water) exposure estimates that are 

below HED’s level of concern (LOC) for the general U.S. population and all population 

subgroups (Memo, G. Kramer, 20-AUG-2013; D410693). Chronic dietary (food and drinking 

water) risk estimates were less than ≤8.5% of the chronic population-adjusted dose (cPAD). 

Given this dietary risk assessment was performed within the past year, updating the dietary risk 

assessment during Registration Review is not expected unless there are changes to current HED 

policies. 

The residential exposure database is adequate to support the Registration Review process for 

quinoxyfen. Residential exposure/risk assessments may need to be reassessed during 

Registration Review to address updates to HED’s exposure policies.

The occupational exposure database is adequate to support the Registration Review process for 

quinoxyfen. The most recent occupational handler assessment covered the relevant exposure 

scenarios and did not result in risk estimates of concern. Revised occupational handler 

assessments will not be required during Registration Review.

An occupational post-application dermal assessment was not conducted previously due to the 

absence of short- and intermediate-term dermal points of departure (PODs). A quantitative 

occupational post-application assessment will not be necessary during Registration Review. It 

should be noted that chemical-specific dislodgeable foliar residue (DFR) data are available for 

quinoxyfen on grapes (MRID# 45360727), and are currently under review by HED. If, in the 

future, toxicological endpoints change, a dermal occupational post-application assessment will 

incorporate the chemical-specific DFR data.

The following data deficiencies were identified for quinoxyfen:

• Toxicology:

o None.

• Residue Chemistry:

o None.

• Dietary Exposure:

o None.

• Occupational/Residential Exposure:

o None.

EPA anticipates conducting the following risk assessment updates during Registration Review:

• Toxicology: 

o None.
Quinoxyfen Registration Review Human-Health Assessment Scoping Document ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ______________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ____________ ______ ______ ______ __

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• Residue Chemistry: 

o None.

• Dietary Exposure: 

o None.

• Occupational/Residential Exposure: 

o The need for spray drift and volatilization risk assessments for quinoxyfen will be 

examined during Registration Review.

1.0 Introduction

Quinoxyfen is a fungicide used for protection against powdery mildew diseases on a variety of 

crops. There are no residential or non-agricultural uses registered for quinoxyfen. There is 

currently one EP containing quinoxyfen, a 22.58% ai SC formulation (Quintec®, EPA Reg. No. 

62719-375). The most recent human-health risk assessment for quinoxyfen was completed in 

2013 (Memo, G. Kramer et al., 20-AUG-2013 D410691) in conjunction with a registration 

request for use on fruiting vegetables (group 8-10), small fruit vine climbing except fuzzy 

kiwifruit (subgroup 13-07F), and low growing berry (subgroup 13-07G). This memo only 

evaluates the status of the human-health assessments for quinoxyfen.

2.0 Hazard Characterization/Assessment

Radiolabeled quinoxyfen was readily absorbed by rats with peak plasma concentrations 

occurring within 0.5-1.5 hours after administration. Within 24 hours of dosing, 68-85% of the 

dose was recovered in the excreta of all groups. Quinoxyfen was extensively metabolized in rats 

with major metabolites identified in the urine, bile, and feces. The major routes of elimination 

were through the urine and feces. Concentrations of radioactivity were detected in the kidneys, 

liver, ovaries, perirenal fat, gastrointestinal tract, and carcass. Generally, tissue concentrations of 

radioactivity were slightly lower in the males than females.

Quinoxyfen was categorized as having low acute toxicity via the inhalation, oral, and dermal 

routes (Toxicity Category III or IV). It is a mild eye irritant (Toxicity Category III) and 

classified as a dermal sensitizer, but not a dermal irritant.

The primary target organs affected by quinoxyfen are the liver and kidney. The most sensitive 

species was the rat. Liver effects were seen in the subchronic rat and mouse studies as well as 

the chronic dog study. Subchronic effects observed in rats and mice at high doses included 

increased liver weights, hepatocellular hypertrophy, and individual cell hepatocellular necrosis. 

Chronic effects observed in the dog included increased liver weights, increased alkaline 

phosphatase levels, and increased incidence of very slight to slight microscopic hepatic lesions. 

Kidney effects were only noted in the rat combined chronic/carcinogenicity study that resulted in 

an increased severity of chronic progressive glomerulonephropathy in males. Body-weight 

decrements were noted in the rat and/or mouse subchronic, chronic and carcinogenicity studies 

as well as the rabbit developmental and rat reproduction studies.

Oral rat and rabbit developmental studies showed no increased qualitative or quantitative 

susceptibility of offspring to quinoxyfen in utero. In the rabbit developmental toxicity study, 

maternal and developmental toxicity were observed at the highest dose tested (LOAEL = 200 

mg/kg/day). Maternal effects included inanition, clinical signs, decreased body weight and 

body-weight gains, decreased food consumption, and increased incidence of abortion late in 

pregnancy. Developmental toxicity was evidenced as increased incidence of abortion late in 
Quinoxyfen Registration Review Human-Health Assessment Scoping Document ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ______________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ____________ ______ ______ ______ __

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pregnancy. No maternal or developmental toxicity was observed in the rat developmental study 

up to the limit dose of 1000 mg/kg/day. In the two-generation rat reproduction study, no parental 

effects were observed up to the highest dose tested (100 mg/kg/day) while first-generation pup 

weights were reduced at the same dose. In isolation, there is evidence of quantitative 

susceptibility in the two-generation reproduction study, but assessments to parental animals in 

this study are intentionally limited to avoid stressing dams and affecting the rearing and care of 

offspring. If additional evaluations had been performed on parental animals in the twogeneration reproduction study, including histopathology and organ-weight assessments, then it is 

expected that the kidney and liver effects observed in the rat subchronic oral study and in the 

interim (12 months) and final sacrifices of the rat chronic toxicity/carcinogenicity study would 

have been seen at the 100 mg/kg/day dose in the reproduction study. Therefore, when using a 

weight-of-evidence approach that puts the offspring findings in the two-generation reproduction 

toxicity study in context with the full toxicological database, there is no concern for 

susceptibility to offspring since it is anticipated that parental toxicity would have been observed 

at the same dose. 

There is no evidence of carcinogenicity based on studies in rats or mice. Quinoxyfen did not 

show evidence of mutagenicity in in vitro or in vivo studies. 

No evidence of neurotoxicity or neuropathology was seen in any of the submitted studies for 

quinoxyfen.

An immunotoxicity study showed no evidence of immunotoxicity up to the highest dose tested.

Conclusions: The toxicology database is complete to support existing registrations and 

registration review (Attachment 2). No additional toxicological studies are currently required. 

The endpoints from the most recent human-health risk assessment for quinoxyfen (G. Kramer et 

al., 20-AUG-2013 D410691) can be found in Attachment 3. Given this risk assessment was 

performed within the past year, modification of endpoints, doses, or safety factors is not 

expected during registration review unless there are changes to current HED policies.

3.0 Residue Chemistry

Permanent tolerances are established for residues of quinoxyfen per se [40 CFR §180.588 (a)] 

in/on cherries (0.30 ppm); grapes (0.60 ppm); hop, dried cones (3.0 ppm); lettuce, head (7.0 

ppm); lettuce, leaf (19 ppm); pepper, bell (0.35 ppm); pepper, nonbell (1.7 ppm); strawberry 

(0.90 ppm); pumpkin (0.30 ppm); squash, winter (0.30 ppm); and melon subgroup 9A (0.08 

ppm). As indicated above, HED has recently recommended for establishment of tolerances for 

residues of quinoxyfen per se in/on vegetable, fruiting, group 8-10 (1.7 ppm); fruit, small vine 

climbing, except fuzzy kiwifruit, subgroup 13-07F (2.0 ppm); and berry, low growing subgroup 

13-07G (1.0 ppm). There are currently no tolerances for quinoxyfen residues in livestock 

commodities or for inadvertent residues in rotational crops.

Based on acceptable cucumber, grape, sugar beet, and tomato metabolism studies, the nature of 

the residue in plants is adequately understood in the subject crops. Quinoxyfen was the primary 

residue component in all reviewed plant metabolism studies except in wheat grain and straw 

where Metabolite A was the predominant residue. Metabolite A was determined not to be 

associated with the parent quinoxyfen, or related compounds, but was characterized to be highly 

polar and multi-component in nature. In cucumber and tomato, unchanged quinoxyfen remained 

largely on the surface of treated plants. The presence of multiple unidentified polar residues 
Quinoxyfen Registration Review Human-Health Assessment Scoping Document ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ______________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ____________ ______ ______ ______ __

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suggests that metabolism of quinoxyfen does occur to some extent to form more polar soluble 

components with the incorporation into insoluble material. Degradates and conjugates may be 

incorporated into natural constituents such as lignin and cellulose. The HED Metabolism 

Assessment Review Committee (MARC) has determined that the residue of concern for purposes 

of tolerance enforcement and risk assessment is the parent compound only.

There are no livestock feed items associated with the registered crops. Therefore, no livestock 

metabolism studies are required to support current uses of quinoxyfen.

Adequate field trial data are available to support the use of quinoxyfen on the registered crops. 

An adequate number of trials were conducted in the appropriate geographical regions using the 

appropriate formulation applied at the maximum use rate. These studies are also supported by 

adequate storage stability data. The available processing studies for tomato and grape are 

adequate and indicate that separate tolerances are not required for residues in/on any of the 

processed fractions. 

An adequate gas chromatography/mass-selective detector (GC/MSD) method is available for 

enforcing tolerances (DowElanco Procedure ERC95.26); a successful petition method validation 

(PMV) has been completed (Memo, E. Kolbe, 5/11/06; D285350). The lowest level of method 

validation (LLMV) was 0.01 ppm. Quinoxyfen was also successfully recovered using the 

QuEChERS Multiresidue Method (http://www.crlpesticides.eu/library/docs/fv/CRLFV_Multiresidue_methods.pdf).

Dow AgroSciences submitted the results of limited rotational crop field trials for quinoxyfen on 

radish roots and tops, mustard greens, and on wheat grain, forage, hay, and straw conducted at a 

total seasonal application rate of ~0.39 lb ai/A (1X). The study showed that the residues of 

concern [quinoxyfen, 2-oxo-quinoxyfen, and 5,7-dichloro-4-hydroxyquinoline (DCHQ)] are 

each below 0.01 ppm at the 30-day PBI and at all other PBIs that were examined. The 30-day 

PBI on the product labels is thus appropriate.

Conclusions: The residue chemistry database is adequate to support current Registration Review 

data requirements. Adequate metabolism (primary and rotational crops), storage stability, 

magnitude of the residue and processing data are available to support the registered uses. 

Adequate methods are available for enforcement of the currently established tolerances. 

4.0 Dietary Exposure

In 2013, HED conducted chronic dietary exposure analyses for all currently registered and 

proposed food uses of quinoxyfen (Memo, G. Kramer, 20-AUG-2013 D410693). No toxic 

effects attributable to a single (i.e., acute) exposure to quinoxyfen have been identified; 

therefore, an acute dietary exposure assessment has not been conducted. The drinking water 

estimate from the existing/proposed U.S. uses was incorporated directly into the dietary 

assessment using the concentration for surface water generated by the FQPA Index Reservoir 

Screening Tool (FIRST). Assumptions for the chronic assessment included tolerance-level 

residues and 100% crop-treated (CT) for registered and proposed uses, and Dietary Exposure 

Evaluation Model (DEEM) 7.81 default processing factors (where provided). A cancer dietary 

assessment was not conducted because quinoxyfen is classified as “not likely to be carcinogenic 

to humans.” The chronic dietary risk estimates (food and drinking water) are below HED’s LOC 

(<100% of the cPAD) for the general U.S. population and all population subgroups. The most 

highly exposed population subgroup is children 1-2 years old with a risk estimate of 8.5% of the 
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cPAD.

Conclusions: The dietary-exposure database is adequate to support current Registration Review 

requirements. The chronic dietary assessment shows dietary (food + water) risk estimates were 

≤8.5% of the cPAD and were, therefore, below HED’s LOC (i.e., <100% of the cPAD). Given 

this dietary risk assessment was performed within the past year, updating the dietary risk 

assessment during Registration Review is not expected unless there are changes to current HED 

policies.

5.0 Residential Exposure

There are currently no registered uses of quinoxyfen that would result in residential exposure. 

Spray Drift and Volatilization

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

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

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

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

risk assessments. The need for spray drift and volatilization risk assessments for quinoxyfen will 

be examined during Registration Review.

Conclusions: There are currently no registered residential uses for quinoxyfen however; the 

need for spray drift and volatilization risk assessments for quinoxyfen will be examined during 

Registration Review.

6.0 Aggregate-Risk Assessment

The most recent aggregate risk assessment was performed in 2013 (Memo, G. Kramer et al., 20-

AUG-2013 D410691) in conjunction with a registration request for use on fruiting vegetables 

(group 8-10), small fruit vine climbing except fuzzy kiwifruit (subgroup 13-07F), and low 

growing berry (subgroup 13-07G). Short- and intermediate-term assessments, which are used to 

evaluate aggregate dietary and residential exposures, were not performed because there are no 

registered or proposed residential non-food uses. Since there are no residential uses, the chronic 

aggregate risks are made up only of dietary sources (food and drinking water) and the dietary 

exposure analysis represents chronic aggregate exposure. Quinoxyfen is classified as “not likely 

to be carcinogenic to humans”; therefore, a cancer aggregate risk assessment was not performed. 

The chronic aggregate risk estimates do not exceed the HED’s LOC for the general U.S. 

population and all population subgroups.

Conclusions: Given this aggregate risk assessment was performed within the past year, updating 

the aggregate risk assessment during Registration Review is not expected unless there are 

changes to current HED policies.

7.0 Occupational Exposure

Quinoxyfen is a fungicide used for protection against powdery mildew diseases on a variety of 

crops. The agricultural uses of quinoxyfen include artichokes, cucurbit vegetables (group 9), 

grapes, hops, lettuce, peppers, pumpkin, stone fruit (group 12) , and strawberries (Memos, M. 

Dow, 23-APR-2003, D285312; M. Dow, 21-APR-2008, D351766; A. Nowotarski, 15-JUN2010). In addition, there are pending uses on fruiting vegetables (group 8-10), small fruit vine 
Quinoxyfen Registration Review Human-Health Assessment Scoping Document ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ______________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ____________ ______ ______ ______ __

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climbing except fuzzy kiwifruit (subgroup 13-07F), and low growing berry (subgroup 13-07G) 

(Memo, G. Kramer et al., 20-AUG-2013 D410691). The only registered formulation of 

quinoxyfen is a SC formulation (Quintec®; EPA Reg. No 62719-375), with application rates 

ranging from 0.0325 to 0.13 lb ai/A. Quinoxyfen can be applied using aerial or ground 

equipment. Attachment 4 provides a summary of the occupational use patterns.

Based on the current uses, there is a potential for exposure to quinoxyfen in occupational 

scenarios from handling quinoxyfen products during the application process (i.e., mixer/loaders, 

applicators, and mixer/loader/applicators). In addition, there is a potential for post-application 

worker exposure from entering into areas previously treated with quinoxyfen.

Occupational Handlers: There is potential for short- and intermediate-term handler exposures 

from the current uses of quinoxyfen. There is no dermal hazard; therefore, a quantitative dermal 

handler assessment has not been conducted. The short- and intermediate-term inhalation PODs 

are the same; therefore, estimates for short-term durations are protective of longer-term 

inhalation exposure. Chronic exposure is not expected for the current uses. As quinoxyfen is 

classified as “not likely” to be carcinogenic to humans, a cancer risk assessment is not necessary. 

A margin of exposure (MOE) ≥100 is adequate to protect occupational pesticide handlers from 

inhalation exposures.

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

potentially be used, occupational handler exposure is expected from the following exposure 

scenarios: mixing/loading liquids in support of aerial, groundboom, and airblast applications; 

applying liquids with enclosed cockpit aerial, open-cab groundboom, and airblast equipment; 

flagging to support aerial applications; and mixing/loading/applying liquids with mechanicallypressurized handguns. The most recent quantitative occupational handler assessment was 

conducted in conjunction with proposed uses on fruiting vegetables (group 8-10), small fruit vine 

climbing except fuzzy kiwifruit (subgroup 13-07F), and low growing berry (subgroup 13-07G) 

(Memo, J. Tyler, 01-AUG-2013; D410694).

No chemical-specific data were available with which to assess potential exposure to pesticide 

handlers. It is the policy of HED to use the best available data to assess handler exposure. 

Sources of generic handler data, used as surrogate data in the absence of chemical-specific data, 

include Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1), the Agricultural Handler 

Exposure Task Force (AHETF) database, the Outdoor Residential Exposure Task Force 

(ORETF) database, or other registrant-submitted occupational exposure studies. Some of these 

data are proprietary (e.g., AHETF data), and subject to the data protection provisions of the 

Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). The standard values 

recommended for use in predicting handler exposure that are used in this assessment, known as 

“unit exposures,” are outlined in the “Occupational Pesticide Handler Unit Exposure Surrogate 

Reference Tablea

,” which, along with additional information on HED policy on use of surrogate 

data, including descriptions of the various sources, can be found at the Agency websiteb

. 

In the most recent occupational handler assessment, risk calculations were based on maximum 

proposed application rates, and assuming maximum area treated per day (Memo, J. Tyler, 01-

AUG-2013; D410694). Handler's exposure and risk were calculated at baseline (long pants, a 

 a Available: http://www.epa.gov/opp00001/science/handler-exposure-table.pdf b Available: http://www.epa.gov/pesticides/science/handler-exposure-data.html
Quinoxyfen Registration Review Human-Health Assessment Scoping Document ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ______________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ____________ ______ ______ ______ __

Page 9 of 23

long-sleeved shirt, no chemical-resistant gloves, and no respirator) and with PPE when necessary 

(e.g., chemical-resistant gloves, respirators, and engineering controls).

Based on existing registrations, the 01-AUG-2013 assessment identified all of the anticipated 

occupational handler exposure scenarios. In the 01-AUG-2013 assessment, for the scenarios 

where baseline data are available, all inhalation risks for occupational handlers are above the 

LOC (MOE ≥100) with baseline protection (i.e., long-sleeve shirt, long pants, shoes, and socks). 

Only engineering control data (i.e., enclosed cockpits) are available for aerial application 

scenarios. All inhalation risks for occupational aerial applicators are above the LOC (MOE 

≥100) with baseline clothing and enclosed cockpits. The current maximum application rate for 

quinoxyfen is 0.13 lb ai/A. Although the most recent handler assessment was conducted using 

application rates of 0.098-0.11 lb ai/A, the resulting inhalation MOEs were 110,000-9,500,000, 

and were well above the LOC. Therefore, the most recent handler assessment is adequate to 

cover all registered uses of quinoxyfen.

Occupational Post-application: Based on the registered uses, HED has determined that there is 

the potential for occupational post-application exposures to individuals entering areas treated 

with quinoxyfen. However, in the absence of a short- and intermediate-term dermal POD, a 

quantitative dermal post-application exposure assessment is not necessary to support Registration 

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

exposure assessment has not been performed for quinoxyfen to date. However, there are 

multiple potential sources of inhalation exposure to individuals performing post-application 

activities in previously treated fields. These potential sources include volatilization of pesticides 

and re-suspension of dusts and/or particulates that contain pesticides. The Agency sought expert 

advice and input on issues related to volatilization of pesticides from its FIFRA 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 quinoxyfen.

Conclusions: The occupational exposure database is adequate to support the Registration 

Review process for quinoxyfen. The most recent occupational handler assessment covered the 

relevant exposure scenarios and did not result in risk estimates of concern. Revised occupational 

handler assessments will not be required during Registration Review.

An occupational post-application dermal assessment was not conducted previously due to the 

absence of a short- and intermediate-term dermal POD. A quantitative occupational postapplication assessment will not be necessary during Registration Review. It should be noted that 

chemical-specific DFR data are available for quinoxyfen on grapes (MRID# 45360727), and are 

currently under review by HED. If, in the future, toxicological endpoints change, a dermal 

occupational post-application assessment will incorporate the chemical-specific DFR data.

8.0 Public Health and Pesticide Epidemiology Data

For this evaluation, both the OPP Incident Data System (IDS) and the Centers for Disease 

Control and Prevention/National Institute for Occupational Safety and Health (CDC/NIOSH) 
Quinoxyfen Registration Review Human-Health Assessment Scoping Document ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ______________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ____________ ______ ______ ______ __

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Sentinel Event Notification System for Occupational Risk-Pesticides (SENSOR) databases were 

consulted for pesticide incident data on the active ingredient quinoxyfen (Memo, E. Evans and S. 

Recore, D414421, 29-AUG-2013). The purpose of the database search is to identify potential 

patterns in the frequency and severity of the health effects attributed to quinoxyfen exposure. 

For the Main IDS, from 01-JAN-2008 to 11-JUN-2013, there were no incidents reported in the 

database involving quinoxyfen. In Aggregate IDS, from 01-JAN-2008 to 11-JUN-2013, there 

was one reported incident involving quinoxyfen. This incident was classified as minor severity. 

A query of SENSOR-Pesticides from 1998-2009 identifies 11 cases, stemming from seven 

events, involving quinoxyfen. There were no single-ai cases reported. All quinoxyfen cases 

involved multiple active ingredients. One case was high severity, one was moderate severity,

and nine were low severity. The case description for the high severity case states, “A 36 year old 

grape applicator reports that after turning on the air conditioner in the cab of the tractor he could 

smell the pesticide and became ill. He initially reported gastrointestinal, ocular, and respiratory 

symptoms. He sought medical care eight days later for increasing respiratory symptoms.”

Conclusions: Based on the low frequency and generally low severity of incident cases reported 

for quinoxyfen in both IDS and SENSOR-Pesticides, 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 included in the 

Registration Review risk assessment.

9.0 Tolerance Assessment and International Harmonization

Codex MRLs are established for residues of quinoxyfen per se in/on cherries; hops, dry; lettuce, 

head; lettuce, leaf; melons, except watermelon; peppers strawberries, and grapes (Attachment 5). 

U.S. tolerances for residues of quinoxyfen in/on the vegetable, fruiting, group 8-10 (1.7 ppm); 

fruit, stone, group 12 (0.70 ppm); and hop, dried cones (3.0 ppm) are higher than the

corresponding Codex MRLs for peppers (1 ppm); cherries (0.4 ppm); and hops, dry (1 ppm). 

U.S. tolerances for residues of quinoxyfen in/on lettuce, head (7.0 ppm); lettuce, leaf (19 ppm); 

and melon, subgroup 9A (0.08 ppm) are lower than the corresponding Codex MRLs for lettuce, 

head (8 ppm); lettuce, leaf (20 ppm); and melons, except watermelon (0.1 ppm).

Canadian MRLs are established for residues of quinoxyfen per se in/on sweet cherries; tart 

cherries; hop, dried cones; and grapes (Attachment 5). U.S. tolerances for residues of 

quinoxyfen in/on the fruit, stone, group 12 (0.70 ppm); hop, dried cones (3.0 ppm); and fruit, 

small, vine climbing, except fuzzy kiwifruit, subgroup 13-07F (2.0 ppm) are higher than the

corresponding Canadian MRLs for sweet and tart cherries (0.3 ppm); hop, dried cones (2.5 ppm);

and grapes (0.5 ppm). Harmonization issues will be addressed during Registration Review.

10.0 Environmental Justice

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

most recent quinoxyfen human-health risk assessment, in accordance with U.S. Executive Order 

12898, “Federal Actions to Address Environmental Justice in Minority Populations and LowIncome Populationsc

.” The OPP typically considers the highest potential exposures from the 

legal use of a pesticide when conducting human-health risk assessments, including, but not 

limited to, people who obtain drinking water from sources near agricultural areas, the variability 

of diets within the U.S., and people who may be exposed when harvesting crops. Should these 

 c http://www.hss.energy.gov/nuclearsafety/env/guidance/justice/eo12898.pdf
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Page 11 of 23

highest exposures indicate potential risks of concern, OPP further refines the risk assessments to 

ensure that the risk estimates are based on the best available information.

11.0 Cumulative

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 quinoxyfen and any other substances and quinoxyfen 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 quinoxyfen 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/.

12.0 Endocrine Disruption

As required by FIFRA and the Federal Food, Drug, and Cosmetic Act (FFDCA), EPA reviews 

numerous studies to assess potential adverse outcomes from exposure to chemicals. 

Collectively, these studies include acute, subchronic, and chronic toxicity, including assessments 

of carcinogenicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity. 

These studies include endpoints which may be susceptible to endocrine influence, including 

effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual 

maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For 

ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, 

developmental and reproductive effects in different taxonomic groups. As part of its most recent 

registration decision for potassium and sodium nitrate, EPA reviewed these data and selected the 

most sensitive endpoints for relevant risk assessment scenarios from the existing hazard 

database. However, as required by FFDCA section 408(p), potassium and sodium nitrate are 

subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list 
Quinoxyfen Registration Review Human-Health Assessment Scoping Document ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ______________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ____________ ______ ______ ______ __

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of chemicals identified for EDSP screening was published on June 14, 2013d and includes some 

pesticides scheduled for Registration Review and chemicals found in water. For further 

information on the status of the EDSP, the policies and procedures, the lists of chemicals, future 

lists, the test guidelines and the Tier 1 screening battery, please visit our websitee. 

In the interim, EPA is making no human health or environmental safety findings associated with 

the EDSP screening of quinoxyfen. Before completing this Registration Review, the Agency 

will make an EDSP FFDCA section 408(p) determination.

13.0 Human Studies

Past quinoxyfen risk assessments rely in part on data from studies in which adult human subjects 

were intentionally exposed to a pesticide to determine their dermal and inhalation exposure. 

Many such studies, involving exposure to many different pesticides, comprise generic pesticide 

exposure databases such as PHED, the ORETF Database, and the ARTF Database. EPA has 

reviewed all the studies supporting these multi-pesticide generic exposure databases, and has 

found no clear and convincing evidence that the conduct of any of them was either 

fundamentally unethical or significantly deficient relative to the ethical standards prevailing at 

the time the research was conducted. All applicable requirements of EPA’s Rule for the 

Protection of Human Subjects of Research (40 CFR Part 26) have been satisfied, and there is no 

regulatory barrier to continued reliance on these studies.

14.0 Risk Assessment Updates, Data Deficiencies, and Label Revisions

The following data deficiencies were identified for quinoxyfen:

• Toxicology: 

o None.

• Residue Chemistry:

o None. 

• Dietary Exposure: 

o None.

• Occupational/Residential Exposure: 

o None.

EPA anticipates conducting the following risk assessment updates during Registration Review:

• Toxicology: 

o None.

• Residue Chemistry: 

o None.

• Dietary Exposure: 

o None.

• Occupational/Residential Exposure: 

o The need for spray drift and volatilization risk assessments for quinoxyfen will be 

examined during Registration Review.

 d See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of 

chemicals.

e http://www.epa.gov/endo/
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15.0 References

Table 1. Memoranda Relevant to Registration Review.

Author Barcode Date Title

E. Evans & S. 

Recore

D414421 29-AUG-2013 Quinoxyfen: Tier I Review of Human Incidents

J. Tyler D410694 01-AUG-2013 Quinoxyfen. Occupational and Residential Exposure 

Assessment for Proposed Use on Fruiting Vegetable (Group 

8-10), Small Fruit Vine Climbing Except Fuzzy Kiwifruit 

(Subgroup 13-07F), and Low Growing Berry (Subgroup 13-

07G).

G. Kramer et 

al., 

D410691 20-AUG-2013 Quinoxyfen. Human-Health Risk Assessment for the 

Proposed Uses on Vegetable, Fruiting, Group 8-10; Fruit, 

Small Vine Climbing, Except Fuzzy Kiwifruit, Subgroup 13-

07F; and Berry, Low Growing Subgroup 13-07G.

G. Kramer D407728 20-AUG-2013 Quinoxyfen. Petition for the Establishment of Permanent 

Tolerances for Residues in/on Vegetable, Fruiting, Group 8-

10; Fruit, Small Vine Climbing, Except Fuzzy Kiwifruit, 

Subgroup 13-07F; and Berry, Low Growing Subgroup 13-

07G. Summary of Analytical Chemistry and Residue 

Data.

G. Kramer D410693 20-AUG-2013 Quinoxyfen. Chronic Aggregate Dietary (Food and Drinking 

Water) Exposure and Risk Assessment for Tolerances for 

Residues in/on Vegetable, Fruiting, Group 8-10; Fruit, Small 

Vine Climbing, Except Fuzzy Kiwifruit, Subgroup 13-07F; 

and Berry, Low Growing Subgroup 13-07G.

D. Soderberg D392916 28-NOV-2011 Quinoxyfen: Submission of Limited Field Trials on Root, 

Leaf Vegetable and Cereal as Rotated Crops.

A. 

Nowotarski

D375389 15-JUN-2010 Quinoxyfen: Occupational Exposure/Risk Assessment for 

Aerial Application to Stone Fruits, Winter Squash, Gourds, 

Pumpkin, Artichoke, Pepper, Melons, Strawberry, and Head 

and Leaf Lettuce.

S. Levy D374781 24-MAR-2010 Quinoxyfen (055459); Registration No.: 62719-375. Label 

Amendment to Add Aerial Application to Registered Label.

B. Hanson D351021 22-JAN-2009 Quinoxyfen. Human Health Risk Assessment for the 

Proposed Food Use of Quinoxyfen on Stone Fruits Crop 

Group 12 (excluding Cherry), Artichoke, Winter Squash, 

(Pumpkin and Edible Gourds).

W. Carr D354561 02-DEC-2008 Quinoxyfen: Chronic Aggregate Dietary (Food and Drinking 

Water) Exposure and Risk Assessment for the Proposed 

Section 3 Registration on Proposed New Uses of Quinoxyfen 

on Stone Fruits crop group 12 (excluding cherry), Artichoke, 

Winter Squash, Pumpkin and Edible Gourds (PP#8E7325).

D. Wilbur D354559 06-NOV-2008 Quinoxyfen. Petition for Tolerances and Uses on Winter 

Squash (including Pumpkin and Edible Gourd), Artichoke, 

and Stone Fruit (Group 12) (PP#8E7325). Summary of 

Analytical Chemistry and Residue Data.

M. Dow D351766 21-APR-2008 QUINOXYFEN – Occupational Exposure/Risk Assessment 

for the Proposed Use of Quinoxyfen on Stone Fruit, Winter 

Squash and Artichoke

G. Kramer D321331 15-MAY-2006 Quinoxyfen on Peppers (Bell and Non-Bell) (PP#3E6755), 

Eggplant (PP#3E6755), Melon Subgroup 9A (PP#5E6969), 

Strawberry (PP#5E6970), and Lettuce (Head and Leaf) 

(PP#5E6970). Health Effects Division (HED) Risk 

Assessment.
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Table 1. Memoranda Relevant to Registration Review.

Author Barcode Date Title

G. Kramer D323549 12-MAY-2006 Quinoxyfen. Petitions for Tolerances and Uses on Peppers 

(Bell and Non-Bell) (PP#3E6755), Eggplant (PP#3E6755), 

Melon Subgroup 9A (PP#5E6969), Strawberry (PP#5E6970), 

and Lettuce (Head and Leaf) (PP#5E6970). Summary of 

Analytical Chemistry and Residue Data.

S. Stanton D328363 18-APR-2006 Quinoxyfen: Chronic Aggregate Dietary (Food and Drinking 

Water) Exposure and Risk Assessment for the Proposed 

Section 3 Registration on Peppers (PP#3E6755); Melon 

Subgroup 9A (PP#5E6969); Strawberry (PP#5E6970); and 

Lettuce (Head and Leaf) (PP#5E6970).

G. Kramer D277476 13-MAY-2003 PP#s 1E06302 & 2E06474. Quinoxyfen On Grapes, Cherries 

And Hops. Health Effects Division (HED) Risk Assessment.

M. Dow D285312 23-APR-2003 QUINOXYFEN - Exposure/Risk Assessment for Pesticide 

Handlers and Agricultural Workers from the Proposed Uses 

on Cherries, Grapes and Hops.

G. Kramer D276835 26-MAR-2003 PP#s 1E06302 & 2E06474. Quinoxyfen On Grapes, Cherries 

And Hops. Evaluation of Residue Data and Analytical 

Methods. 

G. Kramer D287938 28-FEB-2003 QUINOXYFEN- Briefing Memorandum for Meeting of 

Metabolism Assessment Review Committee.

G. Kramer D285314 23-SEP-2002 PP#1E06302. Quinoxyfen On Grapes And Hops. Request 

for Petition Method Validation (PMV).

G. Kramer D285353 20-SEP-2002 PP#1E06302. Multiresidue Method (MRM) Testing of 

Quinoxyfen.

Attachments: 

Attachment 1: Quinoxyfen Identity Table.

Attachment 2: Toxicology Profile for Quinoxyfen

Attachment 3: Quinoxyfen Endpoint Selection Tables.

Attachment 4: Summary of Registered Occupational Uses.

Attachment 5: Quinoxyfen International Residue Limit Status Sheet.

cc: G. Kramer (RAB1), M. Perron (RAB1), J. Tyler (RAB1)

RDI: RAB1 (8/21/13), D. Vogel (8/29/13)

G.F. Kramer:S10957:PY-S:(703)305-5079:7509P:RAB1
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Attachment 1: Quinoxyfen Identity Table.

Table A1.1. Quinoxyfen Nomenclature.

Chemical Structure

Common name Quinoxyfen

Company name Not applicable

Chemical class Quinoline fungicide

IUPAC name 5,7-dichloro-4-quinolyl 4-fluorophenyl ether

CAS name 5,7-dichloro-4-(4-fluorophenoxy)quinoline

CAS # 124495-18-7

End-use product/EP 2.08 lb ai/gal SC formulation; Quintec® (EPA Reg. No 62719-375) 

Table A1.2. Physicochemical Properties of the Technical Grade Test Compound: Quinoxyfen.1

Parameter Value Reference

Molecular weight 308.13 g/mol

Smith, Amy J., Group B: Physical and 

Chemical Properties of Quinoxyfen 

(DE-795) and Supplemental Properties 

of 3-Hydroxy-XDE-795, Dow 

AgroSciences, LLC, 20 December 

2000.

Melting point/range 106.0-107.5 oC

pH 7.97 (1% solution in water at 22.7 °C)

Density 1.097 g/cm3 at 20 °C

Vapor pressure 1.2 x 10-5 Pa at 20 °C

Log10 KOW (Log P) 4.66 at 20 °C

Solubility

mg/L at 20 °C

Distilled water 0.116

Water (pH 5) 0.128

Water (pH 7) 0.047

Water (pH 5) 0.036

n-Hexane 9.64

Methanol 21.5

Ethyl acetate 179

Toluene 272

Acetone 116

Dichloromethane 589

Dissociation Constant Ka = 2.77 x 10-4, pKa = 3.56 1 Refer to D354559, 11/06/08, D. Wilbur.

N

O

F

Cl

Cl
Quinoxyfen Registration Review Human-Health Assessment Scoping Document ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ______________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ____________ ______ ______ ______ __

Page 16 of 23

Attachment 2: Toxicology Profile for Quinoxyfen

A2.1 Toxicology Data Requirements

Study requirements (40 CFR §158.340) for food use of quinoxyfen are presented 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 Acute Eye Irritation .......................................................

870.2500 Acute Dermal Irritation .................................................

870.2600 Skin Sensitization ..........................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 90-Day Oral Toxicity (rodent).......................................

870.3150 90-Day Oral Toxicity (nonrodent).................................

870.3200 21/28-Day Dermal Toxicity...........................................

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

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

yes

yes

yes

no

no1

yes

yes

yes

--

--

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

870.3700b Prenatal Developmental Toxicity (nonrodent)...............

870.3800 Reproduction and Fertility Effects.................................

yes

yes

yes

yes

yes

yes

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

870.4100b Chronic Toxicity (nonrodent)........................................

870.4200a Carcinogenicity (rat)......................................................

870.4200b Carcinogenicity (mouse)................................................

870.4300 Combined Chronic Toxicity/Carcinogenicity................

yes

yes

yes

yes

yes

yes2

yes

yes2

yes

yes

870.5100 Mutagenicity—Bacterial Reverse Mutation Test ..........

870.5300 Mutagenicity—Mammalian Cell Gene Mutation Test ..

870.5xxx Mutagenicity—Structural Chromosomal Aberrations...

870.5xxx Mutagenicity—Other Genotoxic Effects.......................

yes

yes

yes

yes

yes

yes

yes

yes

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

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

870.6300 Developmental Neurotoxicity........................................

yes

yes

no

yes

yes

--

870.7485 Metabolism and Pharmacokinetics................................

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

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

yes

no

yes

no3

--

yes 1

 HED HASPOC concluded that the 28-day inhalation study was not required at this time (K. Rury, 20-Mar-2013; 

TXR#0056609). 

2

 The combined chronic toxicity/carcinogenicity study satisfies the requirement of the study. 3

 Study is classified as acceptable/non-guideline. The data reported in the study is suitable to inform risk 

assessment in the absence of any further data. 
Quinoxyfen Registration Review Human-Health Assessment Scoping Document ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ______________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ____________ ______ ______ ______ __

Page 17 of 23

A2.2 Toxicity Profiles

Table A2.2.1. Acute Toxicity Profile - Quinoxyfen. 

Guideline No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral (rat) 45360428 LD50 >5000 mg/kg IV

870.1200 Acute dermal (rabbit) 45360501 LD50 >2000 mg/kg III

870.1300 Acute inhalation (rat) 45360504 LC50 >3.38 mg/L IV

870.2400 Acute eye irritation (rabbit) 45360505 Mild eye irritant III

870.2500 Acute dermal irritation (rabbit) 45360508 Not a dermal irritant IV

870.2600 Skin sensitization (guinea pig) 45360511

Buehler Method

Not a dermal 

sensitizer ---

870.2600 Skin sensitization (guinea pig) 45360514

MagnussonKlingman

Dermal sensitizer

---

Table A2.2.2. Subchronic, Chronic, and Other Toxicity Profile - Quinoxyfen.

Guideline No. Study Type

MRID No. (year)/ 

Classification/Doses Results

870.3100 90-Day Oral 

Toxicity in Rodents 

(rat)

45406705, 45406702 

(1992)

Acceptable/guideline

0, 10, 100, 250 mg/kg/day

NOAEL = 10 mg/kg/day.

LOAEL = 100 mg/kg/day based on decreased body 

weight gain in females, increased liver weights in 

males and slight hepatocellular hypertrophy 

(centrilobular and midzonal; both sexes).

870.3100 90-Day Oral 

Toxicity in Rodents 

(mouse)

45406701 (1992)

Acceptable/guideline

0, 10, 50, 100, 250 

mg/kg/day

NOAEL = 100 mg/kg/day.

LOAEL = 500 mg/kg/day based on increased liver 

weights, individual cell hepatocellular necrosis and 

hepatocellular hypertrophy in both sexes.

870.3150 90-Day Oral 

Toxicity in NonRodent (dog)

45406706 (1992)

Acceptable/guideline 

when combined with 

range-finding studies

0, 10, 50, 100 mg/kg/day

Range-finding studies:

45406703 (1992)

0, 100, 500, 1000 

mg/kg/day

45406704 (1993)

0, 250 mg/kg/day

NOAEL = 100 mg/kg/day.

LOAEL = not established.

870.3200 28-Day Dermal 

Toxicity (rat)

45360516 (2000)

Acceptable/guideline

0, 10, 100, 1000 

mg/kg/day

6 hr/day; 5 days/wk

NOAEL = 1000 mg/kg/day.

LOAEL = not established.

870.3700a Prenatal 

Developmental in 

Rodent (rat)

45360520 (1994)

Acceptable/guideline

0, 100, 300, 1000 

mg/kg/day

Maternal NOAEL = 1000 mg/kg/day.

LOAEL = not established.

Developmental NOAEL = 1000 mg/kg/day.

LOAEL = not established.

870.3700b Prenatal 

Developmental in 

Non-Rodent (rabbit)

45360521 (1994)

Acceptable/guideline

0, 20, 80, 200 mg/kg/day

Range finding:

45360519 (1993)

0, 100, 300, 600, 1000 

mg/kg/day

Maternal NOAEL = 80 mg/kg/day.

LOAEL = 200 mg/kg/day based on inanition, 

clinical signs, decreased body weights and bodyweight gains, food consumption, and increased 

incidence of abortion.

Developmental NOAEL = 80 mg/kg/day.

LOAEL = 200 mg/kg/day based on increased 

incidence of abortion.
Quinoxyfen Registration Review Human-Health Assessment Scoping Document ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ______________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ____________ ______ ______ ______ __

Page 18 of 23

Table A2.2.2. Subchronic, Chronic, and Other Toxicity Profile - Quinoxyfen.

Guideline No. Study Type

MRID No. (year)/ 

Classification/Doses Results

870.3800 Reproduction and 

Fertility Effects (rat)

45360522 (1995)

Acceptable/guideline

0, 5, 20, 100 mg/kg/day

Parental/Systemic NOAEL = 100 mg/kg/day.

LOAEL = not established.

Reproductive NOAEL = 100 mg/kg/day.

LOAEL = not established.

Offspring NOAEL = 20 mg/kg/day.

LOAEL = 100 mg/kg/day based on decrease in 

first-generation pup weights.

870.4100a Chronic Toxicity

(rodent)

See 870.4300. See 870.4300.

870.4100b Chronic Toxicity

(dog)

45360517

Acceptable/guideline

0, 5, 20, 200 mg/kg/day

NOAEL = 20 mg/kg/day.

LOAEL = 200 mg/kg/day based on increased 

alkaline phosphatase, increased absolute and 

relative (to body) liver weights, and increased 

incidence of very slight to slight microscopic 

hepatic lesions.

870.4200a Carcinogenicity (rat) See 870.4300. See 870.4300.

870.4200b Carcinogenicity 

(mouse)

45406707 (1995)

Acceptable/guideline

0, 20, 80, 250 mg/kg/day

NOAEL = 80 mg/kg/day.

LOAEL = 250 mg/kg/day based on decreased body 

weight gain in both sexes.

No evidence of carcinogenicity.

870.4300 Combined Chronic 

Toxicity/

Carcinogenicity (rat)

45360523 (1995)

45724201 (2001)

Acceptable/guideline

0, 5, 20, 80 mg/kg/day

NOAEL = 20 mg/kg/day.

LOAEL = 80 mg/kg/day based on increases in 

severity of chronic progressive 

glomerulonephropathy in the males and minimal 

decreases in body weight and body-weight gain in 

the males and females.

870.5100 Bacterial reverse 

mutation

45360601 (1993)

Acceptable/guideline

Negative for inducing reverse mutation in bacteria 

exposed to doses up to 5000 ug/plate (-S9) and 1000 

μg/plate (+S9).

870.5300 In vitro mammalian 

cell gene mutation

45360602 (1994)

Acceptable/guideline

Negative for inducing forward mutation in CHO 

(mammalian) cells treated up to 20 μg/mL (-S9) and 

80 ug/mL (+S9).

870.5375 In vitro mammalian 

chromosome 

aberration (RL)

45360604 (1994)

Acceptable/guideline

Negative up to 100 μg/mL (-S9 and +S9).

870.5395 Mammalian 

micronucleus 

(mouse)

45360603 (1994)

45724203 (2001)

Acceptable/guideline

Negative up to 5000 mg/kg.

870.6200a Acute Neurotoxicity 

Screening Battery 

(rat)

45360515 (1999)

Acceptable/guideline

0, 200, 632, 2000 mg/kg

NOAEL = 2000 mg/kg.

LOAEL = not established.

870.6200b Subchronic 

Neurotoxicity 

Screening Battery 

(rat)

45360518 (1995)

Acceptable/guideline

0, 5, 20, 80 mg/kg/day

NOAEL = 80 mg/kg/day.

LOAEL = not established.
Quinoxyfen Registration Review Human-Health Assessment Scoping Document ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ______________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ____________ ______ ______ ______ __

Page 19 of 23

Table A2.2.2. Subchronic, Chronic, and Other Toxicity Profile - Quinoxyfen.

Guideline No. Study Type

MRID No. (year)/ 

Classification/Doses Results

870.7485 Metabolism and 

Pharmacokinetics

45360605 (1995)

45360606 (2001)

Acceptable/non-guideline

M&F: 10 or 500 mg/kg 

(labeled) as single oral 

dose or 10 mg/kg 

(labeled) as single oral 

dose followed by 10 

mg/kg/day (unlabeled) 

orally for 14 days.

M: 10 or 500 mg/kg 

(labeled) single oral dose 

or 500 mg/kg/day oral 

gavage dose for 3 days.

Absorption of labeled quinoxyfen was rapid with 

maximum plasma concentrations occurring between 

0.5 and 1.5 hours. Overall recovery of the dose 

ranged from 83.5-96.2%. Concentrations of 

radioactivity in the tissues were generally slightly 

lower in males than females and in the low-dose 

compared to the high-dose group. The major 

metabolites identified were an acid labile conjugate 

of 4-fluorophenol and 5,7-dichloro-4-

hydroxyquinoline in the urine, glucuronide and/or 

sulfate conjugate(s) of two isomers of fluorophenyl 

ring-hydroxy-XDE-795 in the bile, and the parent 

and two isomers of fluorophenyl ring-hydroxyXDE-795 (unconjugated) in the feces. The major 

route of elimination was through urine in the 

phenyl-labeled quinoxyfen and through the feces in 

the quinoline-labeled quinoxyfen. 

Classified as non-guideline due to several 

unanalyzed fractions.

870.7800 Immunotoxicity 48106301 (2010)

Acceptable/guideline

0, 20, 100, 250 mg/kg/day

NOAEL = 250 mg/kg/day.

LOAEL = not established. 
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Page 20 of 23

Attachment 3: Quinoxyfen Endpoint Selection Tables.

Table A3.1. Summary of Toxicological Doses and Endpoints for Quinoxyfen for Use in Dietary and NonOccupational Human-Health Risk Assessments.

Exposure/ 

Scenario POD

Uncertainty/

FQPA Safety 

Factors

RfD, PAD, LOC 

for Risk 

Assessment Study and Toxicological Effects

Acute Dietary

(All Populations)

Not 

applicable

Not applicable Not applicable No adverse effects attributable to a 

single dose were observed. As a result, 

no hazard was identified and an 

endpoint was not selected to assess this 

exposure scenario.

Chronic Dietary 

(All Populations)

NOAEL =

20 

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1X

Chronic RfD = 

0.2 mg/kg/day

cPAD = 0.2 

mg/kg/day

Combined chronic 

toxicity/carcinogenicity (rat)

LOAEL = 80 mg/kg/day based on 

increases in severity of chronic 

progressive glomerulonephropathy in 

the males and decreases in body weight 

and body-weight gain in both sexes.

Incidental Oral 

Short-Term (1-30 

days) and 

IntermediateTerm (1-6 

months)

Dermal ShortTerm (1-30 days) 

and IntermediateTerm (1-6 

months)

Inhalation ShortTerm (1-30 days) 

and Intermediateterm (1-6 months)

Not 

applicable

Not applicable Not applicable No exposure is expected because there 

are no residential uses. As a result, 

these exposure scenarios were not 

assessed.

Cancer (oral, 

dermal, 

inhalation)

Classified as “not likely to be carcinogenic to humans” based on the absence of carcinogenicity 

in rats or mice.

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. FQPA SF = FQPA Safety Factor. PAD = population-adjusted dose (a = acute, c = chronic). 

RfD = reference dose. MOE = margin of exposure. LOC = level of concern. 
Quinoxyfen Registration Review Human-Health Assessment Scoping Document ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ______________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ____________ ______ ______ ______ __

Page 21 of 23

Table A3.2. Summary of Toxicological Doses and Endpoints for Quinoxyfen for Use in Occupational 

Human-Health Risk Assessments.

Exposure/ 

Scenario POD UFs

LOC for Risk 

Assessment Study and Toxicological Effects

Dermal

Short-Term (1-

30 days) and 

IntermediateTerm (1-6 

months)

Not 

applicable

Not applicable Not applicable A dermal endpoint was not selected. 

As a result, dermal exposure scenarios 

were not assessed.

Inhalation

Short-Term (1-

30 days) and 

Intermediateterm (1-6 

months)

NOAEL =

20 mg/kg/day

Inhalationabsorption 

factor = 

100%

UFA = 10X

UFH = 10X

Occupational 

LOC for MOE = 

100

90-day oral toxicity (rat)

LOAEL = 100 mg/kg/day based on 

decreased body-weight gain in females, 

increased liver weights in males and 

slight hepatocellular hypertrophy 

(centrilobular and midzonal) in both 

sexes.

Two-generation reproduction toxicity 

study (rat)

LOAEL = 100 mg/kg/day based on a 

decrease in first-generation pup 

weights.

Cancer (oral, 

dermal, 

inhalation)

Classified as “not likely to be carcinogenic to humans” based on the absence of carcinogenicity 

in rats or mice

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. MOE = margin of exposure. LOC = level of concern. 
Quinoxyfen Registration Review Human-Health Assessment Scoping Document ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ______________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ____________ ______ ______ ______ __

Page 22 of 23

Attachment 4: Summary of Registered Occupational Uses.

Quintec® (EPA Reg. #62719-375)

Crop Application 

equipment

Applic. 

Rate (lb 

ai/A)

Max. No. 

Applic. per 

Season

Max. Seasonal 

Applic. Rate 

(lb ai/A)

PHI 

(days) Use Directions and Limitations

Artichokes Aerial and 

ground 0.13 4 0.52 none

Min. RTI = 6-7 days

Min. spray volume = 30 GPA 

(ground); 5 GPA (aerial)

Cherry Ground 0.11 5 0.57 7 Min. RTI = 10-14

Min. spray volume = 30 GPA (ground)

Hops Ground 0.13 4 0.54 21 Min. RTI = 14 days

Min. spray volume = 30 GPA (ground)

Lettuce Aerial and 

ground 0.098 4 0.39 1

Min. RTI = 10-14 days

Min. spray volume = 30 GPA 

(ground); 5 GPA (aerial)

Melons (Subgroup 

9A)

Aerial and 

ground 0.098 4 0.39 3

Min. RTI = 10-14

Min. spray volume = 30 GPA 

(ground); 5 GPA (aerial)

Stone fruit (Group 

12) Ground 0.13 4 0.45 7 Min. RTI = 6-14Min. spray volume = 30 GPA (ground)

Strawberry Aerial and 

ground 0.098 4 0.39 1

Min. RTI = 10-14

Min. spray volume = 30 GPA 

(ground); 5 GPA (aerial)

Winter squash, 

gourds, pumpkin

Aerial and 

ground 0.11 4 0.52 3

Min. RTI = 6-14

Min. spray volume = 30 GPA 

(ground); 5 GPA (aerial)

Fruiting 

Vegetables 

(Subgroup 8-10B)

Aerial and 

ground 0.098 4 0.39 3

Min. RTI = 10-14 days

Min. spray volume = 30 GPA 

(ground); 5 GPA (aerial)

Tomatoes [24(c) 

SLN] Ground 0.098 4 0.39 3 Min. RTI = 7-14 daysMin. spray volume = 20 GPA (ground)

Small Fruit Vine 

Climbing Except 

Fuzzy Kiwifruit 

(Subgroup 13-07F)

Ground 0.11 5 0.54 14 Min. RTI =7-21 days

Min. spray volume = 30 GPA (ground)

Low Growing 

Berry (Subgroup 

13-07G)

Aerial and 

ground 0.098 4 0.39 3

The minimum RTI is 10-14 days

Min. spray volume = 30 GPA 

(ground); 5 GPA (aerial)
Quinoxyfen Registration Review Human-Health Assessment Scoping Document ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ______________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ____________ ______ ______ ______ __

Page 23 of 23

Attachment 5: Quinoxyfen International Residue Limit Status Sheet.

International Residue Limits 

Quinoxyfen (118203; Date of Request: 08/12/2013)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex2

40 CFR 180.588: quinoxyfen, 

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 

quinoxyfen (5,7-dichloro-4-(4-

fluorophenoxy)quinoline)

5,7-dichloro-4-(4-

fluorophenoxy)quinoline

quinoxyfen. The 

residue is fat 

soluble.

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

US Canada Mexico1 Codex2

Artichoke, globe 1.4

Fruit, stone, group 12 0.70 0.3 sweet cherries, tart 

cherries

0.4 cherries

Hop, dried cones 3.0 2.5 1 hops, dry

Gourd, edible 0.20

Lettuce, head 7.0 8

Lettuce, leaf 19 20

Melon, subgroup 9A 0.08 0.1 melons, except 

watermelon

Pumpkin 0.20

Squash, winter 0.20

Vegetable, fruiting, group 8-10 1.7

1 peppers

10 peppers Chili, 

dried

Fruit, small, vine climbing, except 

fuzzy kiwifruit, subgroup 13-07F 2.0 0.5 grapes 2 grapes

Berry, low growing, subgroup 13-07G 1.0 1 strawberry

MRLs with NO US equivalent

Barley 0.01 (*)

Currant, black 1

Edible offal (mammalian) 0.01 (*)

Eggs 0.01 (*)

Meat (from mammals other than 

marine mammals)

0.2 (fat)

Milk fats 0.2

Milks 0.01 

Poultry, meat 0.02 (fat)

Poultry, edible offal of 0.01 

Sugar beet 0.03

Wheat 0.01 (*)

Completed: M. Negussie; 08/16/2013

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

2 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = 

processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the 

fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.