UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: 20-AUG-2013 

OFFICE OF 

CHEMICAL SAFETY ANO 

POLLUTION PREVENTION 

SUBJECT: 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. 

PC Code: 055459 

Decision No.: 4 71748 

Petition No.: 2E81 17 

Risk Assessment Type: Single ChemicaVAggregate 

TXRNo.: NA 

MRIDNo.: NA 

DP Barcode: 0410691 

Registration No.: 62719-375 

Regulatory Action: Sec. 3 Registration 

Case No.: 7037 

CAS No.: 124495-18-7 

40 CFR: § 180.588 

FROM: George 

Jenni

Monique 

fer 

F. 

R. 

M. 

Kramer, 

Tyler, 

Perron, 

Chemist 

Ph.D.

S.D.

, 

, 

Senior 

Toxicologist 

emis ~~ 

Risk Assessment Branch 1 (RAB 1) 

Health Effects Division (HED; 7509P) 

THROUGH: Dana M. Vogel, Acting Branch Chief, RAB ~ 

Associate Division Director, HED (7509P) ~ 

TO: Barbara Madden/Sidney Jackson, RM 05 

Registration Division (RD; 7505P) 

The HED of the Office of Pesticide Programs (OPP) is charged with estimating the risk to human 

health from exposure to pesticides. The RD of OPP has requested that HED evaluate hazard and 

exposure data and conduct dietary, occupational, residential, and aggregate exposure 

assessments, as needed, to estimate the risk to human health that will result from the proposed 

Section 3 registration uses of the active ingredient (ai) quinoxyfen (5,7-dichloro-4-(4-

fluorophenoxy)quinoline) on vegetable, fruiting, group 8-1 0; fruit, small vine climbing, except 

fuzzy kiwifruit, subgroup 13-07F; and berry, low growing subgroup 13-07G. 

A summary of the findings and an assessment of human-health risk resulting from the proposed 

and registered uses of quinoxyfen are provided in this document. The risk assessment, residue 

chemistry assessment, and dietary exposure assessment were provided by George Kramer 

(RAB 1 ); the hazard characterization and endpoint selection by Monique Perron (RAB 1 ); the 

occupational exposure and residential assessment by Jennifer Tyler (RAB 1 ); and the drinking 

water exposure assessment by Karen Milians of the Environmental Fate and Effects Division 

Page I of32 
Quinoxyfen Human-Health Risk Assessment DP#41069l 

(EFED). 

The most recent human-health risk assessment for quinoxyfen, for a Section 3 registration 

request for use on stone fruits crop group 12 (excluding cherry), artichoke, and winter squash, 

was completed on 22-JAN-2009 (B. Hanson, D351021). 

Page 2 of32 
Quinoxyfen Human-Health Risk Assessment DP# 410691

Page 3 of 32

Table of Contents

1.0 Executive Summary ........................................................................................................... 5

2.0 HED Recommendations .................................................................................................... 7

2.1 Data Deficiencies ............................................................................................................ 7

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

2.2.1 Enforcement Analytical Method ............................................................................... 8

2.2.2 Recommended Tolerances......................................................................................... 8

2.2.3 Revisions to Petitioned-For Tolerances.................................................................... 8

2.2.4 International Harmonization..................................................................................... 9

2.3 Label Recommendations................................................................................................ 9

3.0 Introduction........................................................................................................................ 9

3.1 Chemical Identity ........................................................................................................... 9

3.2 Physical/Chemical Characteristics ............................................................................... 9

3.3 Pesticide Use Pattern.................................................................................................... 10

3.4 Anticipated Exposure Pathways................................................................................. 11

3.5 Consideration of Environmental Justice.................................................................... 11

4.0 Hazard Characterization and Dose-Response Assessment.......................................... 11

4.1 Toxicology Studies Available for Analysis................................................................. 11

4.2 Absorption, Distribution, Metabolism, and Excretion (ADME) ............................. 12

4.2.1 Dermal Absorption................................................................................................... 12

4.3 Toxicological Effects .................................................................................................... 13

4.3.1 Summary of Toxicological Effects........................................................................... 13

4.4 Safety Factor for Infants and Children (FQPA Safety Factor) ............................... 13

4.4.1 Completeness of the Toxicology Database.............................................................. 14

4.4.2 Evidence of Neurotoxicity ........................................................................................ 14

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal........ 14

4.4.4 Residual Uncertainty in the Exposure Database ................................................... 14

4.5 Toxicity Endpoint and Point of Departure Selections .............................................. 15

4.5.1 Dose-Response Assessment...................................................................................... 15

4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment..... 16

4.5.3 Cancer Classification and Risk Assessment Recommendation............................ 16

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

Assessment............................................................................................................................... 16

5.0 Dietary Exposure and Risk Assessment......................................................................... 18

5.1 Residues of Concern Summary and Rationale .......................................................... 18

5.2 Food Residue Profile .................................................................................................... 19

5.3 Water Residue Profile.................................................................................................. 19

5.4 Dietary Risk Assessment.............................................................................................. 20

5.4.1 Description of Residue Data Used in Dietary Assessment.................................... 20

5.4.2 Percent Crop Treated Used in Dietary Assessment .............................................. 20

5.4.3 Acute Dietary Risk Assessment............................................................................... 20

5.4.4 Chronic Dietary Risk Assessment........................................................................... 20

5.4.5 Cancer Dietary Risk Assessment............................................................................. 21

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ............................. 21

6.1 Residential (Non-Occupational) Exposure/Risk Characterization ............................. 21

6.2 Residential Bystander Post-application Inhalation Exposure ..................................... 21

6.3 Spray Drift........................................................................................................................ 22

7.0 Aggregate Exposure/Risk Characterization.................................................................. 22

7.1 Acute Aggregate Risk................................................................................................... 22
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7.2 Chronic Aggregate Risk .............................................................................................. 22

8.0 Cumulative Exposure/Risk Characterization ............................................................... 23

9.0 Occupational Exposure/Risk Characterization ............................................................ 23

9.1 Short- and Intermediate-Term Handler Risk ........................................................... 23

9.2 Short- and Intermediate-Term Post-Application Risk............................................. 25

9.2.1 Dermal Post-Application Risk................................................................................. 25

9.2.2 Inhalation Post-Application Risk............................................................................ 25

10.0 References......................................................................................................................... 26

Appendix A. Toxicology Profile and Executive Summaries .................................................. 27

A.1 Toxicology Data Requirements................................................................................... 27

A.2 Toxicity Profiles............................................................................................................ 28

Appendix B. Physical/Chemical Properties............................................................................. 31

Appendix C. Review of Human Research................................................................................ 32
Quinoxyfen Human-Health Risk Assessment DP# 410691

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1.0 Executive Summary

Background: Quinoxyfen is a systemic quinoline fungicide. Its proposed mode of action is the 

inhibition of GTP-binding proteins (G-proteins) affecting intracellular signaling. Quinoxyfen 

was developed for the control of powdery mildews on a variety of crops. 

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).

The Interregional Research Project Number 4 (IR-4) has submitted a Section 3 request to register 

a 22.58% ai suspension-concentrate (SC) formulation (Quintec®, EPA Reg. No. 62719-375) for 

use on vegetable, fruiting, group 8-10; fruit, small vine climbing, except fuzzy kiwifruit, 

subgroup 13-07F; and berry, low growing subgroup 13-07G. The end-use products are proposed 

for 4 to 5 foliar spray applications at 0.098-0.11 lb ai/A/application with minimum retreatment 

intervals (RTIs) of 7-21 days, for maximum seasonal rates of 0.39-0.54 lb ai/A. The proposed 

label allows for applications via aerial and/or groundboom equipment, depending on the crop. 

Preharvest intervals (PHIs) of 1-14 days are proposed. The rotational crop plantback intervals 

(PBIs) are 30 days for all non-labeled crops. In conjunction with this petition, IR-4 has 

requested the establishment of permanent tolerances for the residues of the fungicide quinoxyfen

in or on the commodities summarized in Table 2.2.2.

Hazard Assessment: 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). 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 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. There is apparent 

quantitative susceptibility when looking at the two-generation reproductive study in isolation, but 

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 
Quinoxyfen Human-Health Risk Assessment DP# 410691

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

at the same dose. 

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. 

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.

An immunotoxicity study submitted since the most recent risk assessment showed no evidence 

of immunotoxicity up to the highest dose tested.

The RAB1 risk assessment team for quinoxyfen determined that the Food Quality Protection Act 

(FQPA) Safety Factor (SF) should be reduced to 1X for all exposure scenarios for the following 

reasons (see Section 4.4 for a full discussion): the toxicological database is adequate for FQPA 

assessment, there is no evidence of neurotoxicity, there is low concern for offspring 

susceptibility, and there is no uncertainty in the exposure database, as discussed in Section 4.4.

Food Residue Profile: The nature of the residue in plants is adequately understood in the 

subject crops. Organization for Economic Co-operation and Development (OECD) tolerancecalculation procedures and the submitted residue data sets were used to calculate the HEDrecommended tolerances. There is an adequate residue analytical method for the purposes of 

tolerance enforcement. The submitted magnitude of the residue data are adequate and there are 

no residue chemistry issues that would preclude establishing unconditional tolerances for 

residues of quinoxyfen, as outlined in Table 2.2.2.

Exposure/Risk Assessment Characterization: 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. A chronic risk assessment was conducted for dietary 

exposure based on the existing and proposed uses. The assessment directly incorporated 

drinking water estimates. 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 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 cPAD.

There are no registered or proposed residential uses for quinoxyfen; therefore, a residentialexposure assessment was not conducted.

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”; 
Quinoxyfen Human-Health Risk Assessment DP# 410691

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therefore, a cancer aggregate risk assessment was not performed. The chronic aggregate risk 

estimates do not exceed the HED’s level of concern (LOC) for the general U.S. population and 

all population subgroups.

Based on the proposed use patterns, short- and intermediate-term occupational exposures are 

expected. There are no short-and intermediate-term dermal endpoints or points of departure 

(PODs); therefore, a quantitative dermal handler assessment was not conducted. In addition, the 

short- and intermediate-term inhalation PODs are the same; therefore, estimates for short-term 

durations are protective of longer-term. Chronic occupational exposure is not expected for the 

proposed 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.

For the scenarios where baseline data are available, all short- and intermediate-term inhalation 

risk estimates for occupational handlers are above the LOC (MOE ≥100) with baseline 

protection (i.e., long-sleeved shirt, long pants, shoes, and socks). Only engineering control data 

(i.e., enclosed cockpits) are available for aerial application scenarios. All inhalation risk 

estimates for occupational aerial applicators are above the LOC (MOE ≥100) with baseline 

clothing and enclosed cockpits.

In the absence of a short- and intermediate-term dermal POD, a quantitative short- and 

intermediate-term dermal post-application exposure assessment was not conducted. Based on 

the Agency's current practices, a quantitative non-cancer occupational post-application inhalation 

exposure assessment was not performed for quinoxyfen at this time. 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.

Quinoxyfen is classified in acute Toxicity Category III for acute dermal and primary eye 

irritation. It is classified in Toxicity Category IV for acute oral, acute inhalation and primary 

skin irritation and classified as a dermal sensitizer. The Worker Protection Standard (WPS) 

interim restricted-entry interval (REI) of 12 hours is sufficient to protect workers.

This risk assessment relies in part on data from studies in which adult human subjects were 

intentionally exposed to a pesticide or other chemical. Please refer to Appendix C for a 

discussion of the human study data used in this risk assessment. 

2.0 HED Recommendations

Pending submission of a revised Section F (see Section 2.2.2), there are no other residue 

chemistry, occupational, or toxicology data deficiencies that would preclude the establishment of 

permanent tolerances for residues of quinoxyfen and it metabolites and degradates as outlined in 

Table 2.2.2. 

2.1 Data Deficiencies

860.1550 Proposed Tolerances

The petitioner is requested to submit a revised Section F specifying the following: 
Quinoxyfen Human-Health Risk Assessment DP# 410691

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Revised tolerance expression, as presented in Section 2.2.2.

Revised tolerance levels, as presented in Table 2.2.2.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

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

enforcing quinoxyfen 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. Samples from the submitted field and 

processing studies were analyzed using a high-performance liquid chromatography/mass 

spectrometry (HPLC/MS) method derived from Dow AgroSciences Report RF 98-200 dated 

5/31/99; method entitled “Determination of Residues of Quinoxyfen Applied as EF-1295 in 

Hops.” The LLMV was 0.01 ppm for quinoxyfen in all tomato matrices. 

2.2.2 Recommended Tolerances

In accordance with the most recent guidance concerning tolerance expressions, HED 

recommends that the tolerance expression for 40 CFR §180.588 be changed as indicated below. 

CFR §180.588 (a) General. Tolerances are established for residues of the fungicide 

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).

The proposed uses and the submitted data support the following permanent tolerances for 

residues of quinoxyfen in or on the commodities summarized in Table 2.2.2.

Note to RD: With the establishment of these tolerances, the tolerances for the following 

commodities should be deleted from 40 CFR §180.588 (a): grape; pepper, bell; pepper, nonbell; 

and strawberry.

Table 2.2.2. Tolerance Summary for Quinoxyfen.

Commodity

Proposed 

Tolerance (ppm)

HED-Recommended 

Tolerance (ppm)

Comments; Correct Commodity 

Definition

Vegetable, fruiting, group 8-

10 1.7 1.7

Fruit, small, vine climbing, 

except fuzzy kiwifruit, 

subgroup 13-07F

0.60 2.0

Berry, low growing, 

subgroup 13-07G 0.90 1.0

2.2.3 Revisions to Petitioned-For Tolerances

HED is recommending increases in the proposed tolerances for residues of quinoxyfen in/on the 

berry, low growing subgroup 13-07G and the fruit, small, vine climbing, except fuzzy kiwifruit, 

subgroup 13-07F in order to harmonize with the Codex maximum residue limits (MRLs; see 
Quinoxyfen Human-Health Risk Assessment DP# 410691

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Section 2.2.4).

2.2.4 International Harmonization

Codex MRLs are established for residues of quinoxyfen per se in/on grapes, strawberries, and 

peppers. HED is recommending increases in the proposed U.S. tolerances for residues of 

quinoxyfen in/on the berry, low growing subgroup 13-07G and the fruit, small, vine climbing, 

except fuzzy kiwifruit, subgroup 13-07F in order to harmonize with the Codex MRLs. 

Harmonization of the proposed U.S. tolerance for residues of quinoxyfen in/on the vegetable, 

fruiting, group 8-10 (1.7 ppm) with the Codex MRL for peppers (1 ppm) is not possible as the 

U.S. tolerance would need to be reduced significantly (residue data from field trials conducted in 

the U.S. show that the Codex MRL is too low).

Harmonization with the Canadian MRL for grapes (0.5 ppm) is not possible because 

harmonization with the Codex MRL necessitates a higher tolerance (2.0 ppm) for residues of 

quinoxyfen in/on the fruit, small, vine climbing, except fuzzy kiwifruit, subgroup 13-07F.

2.3 Label Recommendations

The proposed label (Quintec®; EPA Reg. No 62719-375) lists the maximum application rate for 

tomato as 6 oz product/gal, which equates to 0.098 lb ai/A [(6 oz product/gal) x (1 gal/128 oz) x 

(2.08 lb ai/gal) = 0.098 lb ai/A]. This rate differs from Section B of the petition, which lists the 

maximum application rate for tomatoes as 0.13 lb ai/A. HED requests clarification of the 

intended application rate for tomatoes.

3.0 Introduction

3.1 Chemical Identity

Table 3.1. 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) 

N

O

F

Cl

Cl
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3.2 Physical/Chemical Characteristics

Quintec®is a protectant fungicide used to control powdery mildew infections on grapes and

hops. Quintec®cannot control existing or latent infections; therefore, the pesticide must be

applied before infections occur. Quinoxyfen has chemical properties that imply that it may be 

persistent in the environment under certain conditions. However, once it is in the soil, the 

studies show quinoxyfen is immobile to slightly mobile depending on the soil type. Quinoxyfen 

is rapidly metabolized under aquatic conditions, but more stable under terrestrial conditions. The 

water solubility and the Kd/Koc values indicate quinoxyfen is fairly insoluble and will adsorb 

tightly to soil particles. Its vapor pressure is 1.2 x 10-5Pa at 20 oC. A summary of the 

physicochemical properties can be found in Appendix B. 

3.3 Pesticide Use Pattern

There is currently one quinoxyfen end-use product (EP) registered to Dow AgroSciences LLC 

for use on food/feed crops: Quintec®, a 22.58% ai SC (EPA Reg. No. 62719-375). IR-4 is 

supporting the use of Quintec®on vegetable, fruiting, group 8-10; fruit, small vine climbing, 

except fuzzy kiwifruit, subgroup 13-07F; and berry, low growing subgroup 13-07G. Example 

labels were provided and the proposed use directions are summarized in Table 3.3.1.

Table 3.3.1. Summary of Proposed Use Directions for Quinoxyfen.

Application Timing, Type 

and Equipment

Formulation

[EPA reg. No.]

Single 

Rate

(lb ai/A)

Max Number 

Applications 

per Season

Max. Seasonal 

Application 

Rate (lb ai/A)

PHI 

(Days)

Use Directions 

and 

Limitations1

Vegetable, Fruiting, Group 8-10

Directed foliar applications 

Ground equipment

Quintec®

[62719-375]

0.098 4 0.39 3 The minimum 

retreatment 

interval (RTI) 

is 7-14 days.

Fruit, Small Vine Climbing, Except Fuzzy Kiwifruit, Subgroup 13-07F

Directed foliar applications 

Ground equipment

Quintec®

[62719-375]

0.11 5 0.54 14 The minimum 

RTI is 7-21 

days.

Berry, Low Growing Subgroup 13-07G

Directed foliar applications 

Ground equipment

Quintec®

[62719-375]

0.098 4 0.39 1 The minimum 

RTI is 10-14 

days.

1

 Crops having quinoxyfen tolerances may be replanted at any time, all other crops require a 30-day PBI.

Conclusions: The proposed use patterns are adequate to allow evaluation of the residue data 

submitted in support of this petition. 

It should be noted that the proposed label (Quintec®) lists the maximum application rate for 

tomato as 6 oz product/gal, which equates to 0.098 lb ai/A [(6 oz product/gal) x (1 gal/128 oz) x 

(2.08 lb ai/gal) = 0.098 lb ai/A]. This rate differs from Section B of the petition, which lists the 

maximum application rate for tomatoes as 0.13 lb ai/A. HED requests clarification of the 

intended application rate for tomatoes. For the purposes of this risk assessment, HED assumed 

the proposed label rate to be correct.
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3.4 Anticipated Exposure Pathways

RD has requested that HED evaluate hazard and exposure data and conduct dietary, 

occupational, residential, and aggregate exposure assessments, as needed, to estimate the risk to 

human health that will result from the proposed Section 3 registration uses of quinoxyfen on 

vegetable, fruiting, group 8-10; fruit, small vine climbing, except fuzzy kiwifruit, subgroup 13-

07F; and berry, low growing subgroup 13-07G. Humans may be exposed to quinoxyfen in food 

and drinking water, since quinoxyfen may be applied directly to growing crops and application 

may result in quinoxyfen reaching surface and ground water sources of drinking water. There 

are no residential uses of quinoxyfen, so exposure in residential or non-occupational settings is 

not likely. In an occupational setting, applicators may be exposed while handling the pesticide 

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

exposure for workers re-entering treated fields. 

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

proposed new uses of quinoxyfen, but also considers the existing registered uses as well. 

3.5 Consideration of Environmental Justice

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

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

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

(http://www.hss.energy.gov/nuclearsafety/env/guidance/justice/eo12898.pdf). As a part of every 

pesticide risk assessment, OPP considers a large variety of consumer subgroups according to 

well-established procedures. In line with OPP policy, HED estimates risks to population 

subgroups from pesticide exposures that are based on patterns of that subgroup’s food and water 

consumption, and activities in and around the home that involve pesticide use in a residential 

setting. Extensive data on food consumption patterns are compiled by the U.S. Department of 

Agriculture (USDA) under the National Health and Nutrition Examination Survey, What We Eat 

in America, (NHANES/WWEIA; 2003-2008) and are used in pesticide risk assessments for all 

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

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

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

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

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

for toddlers, youths, and adults entering or playing on treated areas postapplication are evaluated. 

Further considerations are currently in development as OPP has committed resources and 

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

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

subgroups.

4.0 Hazard Characterization and Dose-Response Assessment

Quinoxyfen is a quinoline fungicide that acts by inhibiting GTP-binding proteins (G-proteins) in 

intracellular signaling.

4.1 Toxicology Studies Available for Analysis

This assessment includes summaries from the most recent human-health risk assessment for 
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quinoxyfen (B. Hanson, 22-JAN-2009; D351021). The toxicological database for quinoxyfen is 

adequate for hazard characterization, toxicity endpoint selection, and FQPA SF evaluation. An 

immunotoxicity study (MRID# 48106301) has been submitted since the last risk assessment and 

the results incorporated into the current assessment. An in vivo dermal penetration study 

(MRID# 47830401) has been submitted and classified as acceptable/non-guideline. In the 

absence of any further information, the results of this study can be used for risk assessment 

purposes.

The classification of the rat metabolism study (MRID#s 45360605 and 45360606) has been 

changed from unacceptable/upgradable to acceptable/non-guideline (M. Perron, 26-MAR-2013; 

TXR# 0056612) since the last risk assessment. It is suitable at this time for risk assessment in 

the absence of any further data. If a need for additional metabolic information for quinoxyfen 

arises that may affect future risk assessments, then the classification of this study may be 

reevaluated. 

HED previously requested a 28-day inhalation study to characterize the effects of quinoxyfen via 

the inhalation route. The HED Hazard and Science Policy Council (HASPOC) concluded, using 

a weight-of-evidence approach, that the 28-day inhalation study was not required at this time (K. 

Rury, 20-MAR-2013; TXR# 0056609).

4.2 Absorption, Distribution, Metabolism, and Excretion (ADME)

Following oral administration of radiolabeled quinoxyfen ([2-Quinoline14C] XDE-795), peak 

plasma concentrations occurred within 0.5-1.5 hours for all treatment groups. Plasma clearance 

of radioactivity was biphasic with a half-life ≤1 hour for the rapid/primary phase and 15-19 

hours for the slower/secondary phase at the low dose. At the higher dose of 500 mg/kg, the 

clearance half-life values increased to 2-3 hours and 18-22 hours for the rapid and slow phases, 

respectively, suggesting saturation of clearance at this higher dose level. In the bile-ductcannulated male rats, 14.3% dose was found in the feces at 10 mg/kg and 57.3% dose at 500 

mg/kg, indicating that the fraction unabsorbed increases with the higher dose level tested. 

Within 24 hours of dosing, 68-85% 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 for both radiolabels of 

quinoxyfen (45-49% urine and 38-40% feces for [Phenyl-U14C] XDE-795; 13-20% urine and 

66-78% feces for [2-Quinoline14C] XDE-795). Concentrations of radioactivity were detected in 

the kidneys, liver, ovaries, perirenal fat, gastrointestinal (GI) tract, and carcass. Generally, tissue 

concentrations of radioactivity were slightly lower in the males than females and lower in the 10-

mg/kg group than the 500-mg/kg group.

4.2.1 Dermal Absorption

A dermal-absorption factor of 34% was identified from the maximum systemic absorption 

observed in the rat dermal penetration study (MRID# 47830401). A dermal-absorption factor 

was not needed for this risk assessment because no dermal endpoint was chosen (Section 4.5.1).
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4.3 Toxicological Effects

4.3.1 Summary of Toxicological Effects

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 

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. There is apparent quantitative susceptibility when 

looking at the two-generation reproductive study in isolation, but when using a weight-ofevidence 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

(see section 4.4.3). 

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. 

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.

An immunotoxicity study submitted since the most recent risk assessment showed no evidence 

of immunotoxicity up to the highest dose tested.

4.4 Safety Factor for Infants and Children (FQPA SF)

The RAB1 risk assessment team for quinoxyfen determined that the FQPA SF should be reduced 

to 1X for all exposure scenarios for the following reasons: the toxicological database is adequate 

for FQPA assessment, there is no evidence of neurotoxicity, there is low concern for offspring 

susceptibility, and there is no uncertainty in the exposure database.
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4.4.1 Completeness of the Toxicology Database

The existing toxicological database is adequate for characterizing quinoxyfen toxicity and 

quantification of hazard for dietary and occupational exposures. The developmental toxicity 

studies in rats and rabbits, two-generation reproduction toxicity study in rats, and acute and 

subchronic neurotoxicity studies are available to assess potential fetal/offspring sensitivity.

4.4.2 Evidence of Neurotoxicity

There is no evidence of neurotoxicity from quinoxyfen exposure. A developmental 

neurotoxicity study was not required since there was no evidence of neurotoxicity or 

neuropathology in the acute or subchronic neurotoxicity studies or any other submitted study.

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

In isolation, there is evidence of increased quantitative susceptibility in the two-generation 

reproduction toxicity 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. Concern is low 

since: 1) the effects in pups are well characterized with a clear no-observed adverse-effect level 

(NOAEL); 2) the pup effects are only noted in the first-generation offspring; and 3) the doses 

and endpoints selected for risk assessment are protective of the pup effects noted in the rat 

reproduction study. Additionally, taking into consideration the full toxicological database, there 

would be no susceptibility to offspring since assessments to parental animals are intentionally

limited in the two-generation reproduction study 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. 

 

In utero exposure in developmental studies did not display quantitative or qualitative evidence of 

increased susceptibility of rat or rabbit offspring.

4.4.4 Residual Uncertainty in the Exposure Database

The chronic dietary food exposure assessment utilizes existing and proposed tolerance-level 

residues, DEEM 7.81 default processing factors (where provided), and 100% CT information for 

all commodities. By using these screening-level assessments, actual exposures/risks will not be 

underestimated.

The dietary drinking water assessments utilize water concentration values generated by the 

FQPA Index Reservoir Screening Tool (FIRST) model. The resulting screening-level estimated 

drinking water concentrations (EDWCs) provide conservative, health-protective, high-end 

estimates of water concentrations that will not likely be exceeded.
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There are no registered residential uses of quinoxyfen; therefore, residential exposures are not 

anticipated. 

4.5 Toxicity Endpoint and Point of Departure Selections

Changes were made to the occupational toxicity endpoints since the last risk assessment. A 

dermal endpoint was not selected therefore occupational dermal exposures were not assessed. 

Additionally, the subchronic oral and the two-generation reproduction toxicity studies in rats 

were considered co-critical studies for occupational inhalation exposures. The PODs, 

uncertainty factors (UFs), and toxicity endpoints are presented in Table 4.5.4.1 (dietary and nonoccupational assessments) and Table 4.5.4.2 (occupational assessments). 

4.5.1 Dose-Response Assessment

Acute Dietary Endpoint (all populations): There were no effects observed attributable to a single 

dose for the general population (including infants and children) or females 13-49 years of age; 

therefore, an endpoint was not selected for this exposure scenario. There were no effects seen in 

the acute neurotoxicity study up to the limit dose. Abortions observed in the rabbit 

developmental study were not considered an appropriate endpoint for females 13-49 years of age 

because abortions occurred late in pregnancy in the presence of substantial maternal toxicity. 

Chronic Dietary Endpoint (all populations): The chronic reference dose (cRfD) was established 

based on the NOAEL (20 mg/kg/day) from the rat combined chronic toxicity/carcinogenicity 

study. The LOAEL of 80 mg/kg/day is based on increases in severity of chronic progressive 

glomerulonephropathy in the males and minimal decreases in body weight and body-weight gain 

in both sexes. The NOAEL of 20 mg/kg was chosen because the study and endpoint are 

appropriate for the route and duration of exposure. The cRfD of 0.2 mg/kg/day is derived from 

the NOAEL of 20 mg/kg/day and a 100-fold uncertainty factor (10X for interspecies 

extrapolation, 10X for intraspecies variation, and 1X for FQPA SF). For reasons outlined in 

Section 4.4, the FQPA SF has been reduced to 1X for this exposure scenario.

Short- and Intermediate-Term Incidental Oral Exposure: There are no registered or proposed 

residential uses for quinoxyfen. Therefore, an endpoint for incidental oral exposure was not 

selected. 

Short- and Intermediate-Term Dermal Endpoints: A dermal endpoint was not selected. Dermal 

endpoints were chosen in previous risk assessments; however, reevaluation of the full 

toxicological database yielded no dermal hazard. Since there is no concern for enhanced 

sensitivity/susceptibility to offspring from quinoxyfen exposure (as discussed in Section 4.4.3), 

the effects of concern in adults and offspring are adequately assessed in the dermal toxicity study 

where no adverse dermal or systemic effects were observed up to the limit dose (1000 

mg/kg/day).

Short- and Intermediate-Term Inhalation Endpoints: The subchronic oral and two-generation 

reproduction toxicity studies in rats were chosen as co-critical studies for the short- and 

intermediate-term occupational inhalation scenarios. The LOAEL of 100 mg/kg/day in the 

subchronic oral study was based on decreased body-weight gain in females, increased liver 

weights in males and slight hepatocellular hypertrophy in both sexes. The LOAEL of 100 

mg/kg/day in the two-generation reproduction study was based on decreased first generation pup 
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weights. The NOAEL in the subchronic oral study (10 mg/kg/day) is lower than the NOAEL in 

the two-generation reproduction study (20 mg/kg/day), but this is a reflection of dose selection. 

Therefore, the NOAEL from the two-generation reproduction study of 20 mg/kg/day is 

protective of effects seen in both studies. The LOC for inhalation exposure scenarios is for 

MOEs <100 (10X for interspecies extrapolation and 10X for intraspecies variation). For 

inhalation exposure scenarios, 100% absorption of the oral dose should be assumed. 

4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment

For occupational risk, only inhalation exposures are of concern. Currently, there are no 

registered residential uses of quinoxyfen.

4.5.3 Cancer Classification and Risk Assessment Recommendation

The Agency classified quinoxyfen as “not likely to be carcinogenic to humans” by all routes of 

exposure based upon lack of evidence of carcinogenicity in rats and mice; therefore, a cancer risk 

assessment is not required.

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

Assessment

Table 4.5.4.1. Summary of Toxicological Doses and Endpoints for 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.
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Table 4.5.4.1. 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

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. 

Table 4.5.4.2. 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.
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Table 4.5.4.2. 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

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. 

5.0 Dietary Exposure and Risk Assessment 

An overview of the metabolism and environmental degradation of quinoxyfen can be found in 

the 22-JAN-2009 human-health risk assessment (B. Hanson, D351021).

5.1 Residues of Concern Summary and Rationale

Plants (Primary 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. 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 (D227383, G. Kramer, 26-MAR-2003).

Plants (Rotational Crops): Dow AgroSciences previously 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 residues of quinoxyfen, 2-oxo-quinoxyfen, and DCHQ are each below 0.01 

ppm at the 30-day PBI and at all other PBIs that were examined. The proposed 30-day PBI on 

the product labels is appropriate.

Livestock: There are no livestock feed items associated with the subject crops. Therefore, data 

requirements related to livestock (e.g., metabolism studies, methods, magnitude of the residue) 

are not pertinent to this petition.

Drinking Water: Environmental fate data suggest that parent is persistent in the environment 

and is stable to hydrolysis at pH 7 and 9, only susceptible to hydrolysis under acidic conditions 

(pH 4). The three major metabolites are: DCHQ (86% applied dose in hydrolysis at pH 4 in 4 

days, 3% at pH 7 in 21 days), CFBPQ (91% in aqueous photolysis), and 3-OH-quinoxyfen (62% 

applied dose in aerobic soil metabolism). Under typical environmental pH ranges, DCHQ is not 

likely to be found in drinking water sources in substantial quantities; therefore, it can be 

excluded as a residue of concern. CFBPQ degraded rapidly as the aqueous photolysis study 

continued, with an estimated half-life of 7 hours, and can also be excluded as a residue of 

concern. 3-OH-quinoxyfen is stable in soil and there is a possibility of accumulation with 

multiple applications. Due to the lack of soil partitioning data on this metabolite, there is 

uncertainty concerning its mobility. Because hydroxylation (the addition of the 3-OH) is 

assumed to increase mobility relative to quinoxyfen, it is presumed to have the potential to reach 

drinking water sources in significant quantities. Based on the structure similarity, this metabolite 
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might have similar toxicity as the parent. Therefore, MARC recommends that for risk 

assessment, parent and 3-OH-quinoxyfen are the residues of concern (D227383, G. Kramer, 26-

MAR-2003).

Table 5.1. Summary of Metabolites and Degradates to be included in Risk Assessment and Tolerance 

Expression1.

Matrix Residues Included in Risk Assessment Residues Included in Tolerance Expression 

for Compliance Monitoring

Plants

Subject

Crops

2 Quinoxyfen Quinoxyfen

Rotational 

Crop Not Applicable3 Not Applicable3

Drinking Water Quinoxyfen and 3-OH-quinoxyfen Not Applicable

1 Memo, G. Kramer, 20-AUG-2013; D407728.

2

For future new uses (i.e., on small grains), additional metabolism data may be required.

3 The following potential residues of concern were identified: quinoxyfen, 2-oxo-quinoxyfen, and DCHQ. None of these 

residues were found in the limited rotational crop field trials at a 30-day PBI. Provided a 30-day PBI is specified on the 

quinoxyfen labels and use rates are 0.39 lb ai/A or below for annual crops, residues in rotational crops are not currently of 

concern for the risk assessment or for tolerance setting.

5.2 Food Residue Profile

The submitted field trial residue data for tomatoes are adequate. The field trial data reflect the 

proposed use pattern; an adequate number of trials were conducted in the appropriate geographic 

regions; and samples were analyzed for the residue of concern using validated data-collection 

methods. The storage intervals were also validated. Using the OECD tolerance calculation 

procedures for the residue data indicate that the requested tolerance level for vegetable, fruiting, 

group 8-10 is appropriate. In addition, the previously submitted data on strawberries and grapes 

are adequate to support the expansion to the low-growing berry 13-07G crop subgroup and the 

small fruit vine climbing subgroup 13-07F, except fuzzy kiwifruit, respectively.

The newly submitted tomato and the previously submitted grape processing studies are also 

adequate. Separate tolerances are not required for residues in/on any of the processed fractions. 

Dow AgroSciences previously 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 

(1X the proposed rate). The study showed all residues of concern were 0.01 ppm at the 30-day 

PBI and at all other PBIs that were examined. The proposed 30-day PBI is appropriate.

5.3 Water Residue Profile

EFED provided Tier 1 ground and surface EDWCs for quinoxyfen and the major transformation 

product, 3-OH-quinoxyfen (Memo, K. Milians, 04-23-13; D407730). Quinoxyfen is proposed 

for use by both aerial and ground application, with a single maximum application rate of 0.107 

lbs ai/A (6.6 fl oz ai/A/application Quintec®) and a seven day minimum re-application interval, 

for a maximum total application rate of 0.54 lbs ai/A/year (33 fl oz ai/A/year Quintec®). 

Because the new uses are proposed at lower maximum application rates than those for previously 

assessed uses, EFED refers to the last assessment, dated October 20, 2008 (D351023). 

The last drinking water assessment for quinoxyfen focused on the use on stone fruit group 12 

(excluding cherries), artichokes, winter squash, pumpkins, and edible gourds. EDWCs were 
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estimated using the FIRST model for surface water and the SCI-GROW model for groundwater 

(EDWCs using PRZM-GW were negligible, and thus do not supersede the SCI-GROW 

EDWCs). In that assessment (D351023), EDWCs were determined based on an annual 

application rate of 0.57 lb ai/A (five applications at 0.114 lb ai/A, with a re-application interval 

of seven days), and an annual application rate of 0.52 lb ai/A (four applications at 0.13 lb ai/A, 

with a re-application interval of six days). 

Table 5.3. Tier I EDWCs Resulting From Applications of Quinoxyfen.

Use Pattern

(Surface Water/FIRST 

model)

Use

(modeled rate) Acute (ppb) Chronic (ppb)

Groundwater 

(SCIGROW) ppb

Surface water

Stone Fruits

(FIRST)

Aerial spray

(0.13lb ai/A x 4 applic.; total of 0.52 

lb/A/yr)

9.3 0.66 3.1 x 10-3

Surface water 

Cherries

(FIRST)

Orchard air blast spray

(0.114 lb ai/A x 5 applic.; total of 

0.57 lb/A/yr)

9.9 0.62 3.4 x 10-3

Values in bold show the highest EDWCs, which are recommended for use in dietary risk assessment. 

5.4 Dietary Risk Assessment

5.4.1 Description of Residue Data Used in Dietary Assessment

A chronic dietary-exposure and risk assessment was conducted using DEEM-FCID, ver. 3.16 

which incorporates consumption data from the USDA NHANES/WWEIA; 2003-2008. The 

assessments were performed for the general U.S. population and all population subgroups. The 

unrefined chronic analysis assumed DEEM 7.81 default concentration factors, and tolerancelevel residues for all commodities. The drinking water estimate from the existing U.S. uses was 

incorporated directly into the dietary assessment using the concentration for surface water 

generated by the FIRST. The resulting screening-level EDWC estimate of 0.00066 ppm was 

used for the chronic assessment. 

5.4.2 Percent Crop Treated Used in Dietary Assessment

The chronic dietary analysis assumed 100% CT for all commodities. 

5.4.3 Acute Dietary Risk Assessment

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. 

5.4.4 Chronic Dietary Risk Assessment

The chronic dietary risk estimates (food + water) were 2.4% of the cPAD for the general U.S. 

population and 8.5% of the cPAD for the most highly exposed population subgroup (children 1-2 

years old) and are thus below HED’s level of concern (>100% cPAD). A summary table of 

dietary exposure and risk for quinoxyfen can be found in Section 5.4.6. Although further 

refinement to the analysis is not required at this time, future assessments could be refined using

average field trial values, use of empirical processing factors, incorporation of % CT data, or 
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monitoring data. 

5.4.5 Cancer Dietary Risk Assessment

A cancer dietary assessment was not performed because quinoxyfen was classified as “not likely 

to be carcinogenic to humans.”

5.4.6 Summary Table

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

Population Subgroup

Acute Dietary (95th Percentile) Chronic Dietary

Dietary Exposure 

(mg/kg/day) % aPAD

Dietary Exposure

(mg/kg/day) % cPAD

General U.S. Population N/A N/A 0.006582 3.3

All Infants (<1 year old) N/A N/A 0.005601 2.8

Children 1-2 years old N/A N/A 0.016903 8.5

Children 3-5 years old N/A N/A 0.014353 7.2

Children 6-12 years old N/A N/A 0.007967 4.0

Youth 13-19 years old N/A N/A 0.005047 2.5

Adults 20-49 years old N/A N/A 0.005882 2.9

Adults 50-99 years old N/A N/A 0.005669 2.8

Females 13-49 years old N/A N/A 0.005907 3.0

*The values for the highest exposed population for each type of risk assessment are bolded.

6.0 Residential (Non-Occupational) Exposure/Risk

6.1 Residential Exposure/Risk Characterization

There are no registered or proposed uses of quinoxyfen that result in residential exposures. 

Therefore, residential exposure is not expected, and no residential risk assessment was 

performed. 

6.2 Residential Bystander Post-Application Inhalation Exposure

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

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

inhalation toxicity (Toxicity Category IV) and the low proposed use rate (0.11 lb ai/A). 

However, volatilization of pesticides may be a source of post-application inhalation exposure to 

individuals nearby pesticide applications. The Agency sought expert advice and input on issues 

related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act 

(FIFRA) Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report 

on March 2, 20101. The Agency is in the process of evaluating the SAP report and may, as 

appropriate, develop policies and procedures to identify the need for and, subsequently, the way 

to incorporate post-application inhalation exposure into the Agency's risk assessments. If new 

policies or procedures are developed, then the Agency may revisit the need for a quantitative 

post-application inhalation exposure assessment for quinoxyfen.

 

1 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html
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6.3 Spray Drift

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

This is particularly the case with aerial application, but, to a lesser extent, could also be a 

potential source of exposure from the ground application method employed for quinoxyfen. The 

Agency has been working with the Spray Drift Task Force, EPA Regional Offices, and State 

Lead Agencies for pesticide regulation and other parties to develop the best spray-driftmanagement practices (see the Agency’s Spray Drift website for more information2

. The 

Agency has completed its evaluation of the new database submitted by the Spray Drift Task 

Force, a membership of U.S. pesticide registrants, and is developing a policy on how to 

appropriately apply the data and the AgDRIFT®computer model to its risk assessments for 

pesticides applied by air, orchard airblast and ground hydraulic methods. After the policy is in 

place, the Agency may impose further refinements in spray-drift-management practices to reduce 

off-target drift with specific products with significant risk estimates associated with drift.

7.0 Aggregate Exposure/Risk Characterization

In accordance with the FQPA, HED must consider and aggregate pesticide exposures and risks 

from three major sources: food, drinking water, and residential exposures. In an aggregate 

assessment, exposures from relevant sources are added together and compared to quantitative 

estimates of hazard (e.g., a NOAEL or PAD), or the risks themselves can be aggregated. When 

aggregating exposures and risks from various sources, HED considers both the route and 

duration of exposure.

For quinoxyfen, an aggregate exposure risk assessment was performed for chronic aggregate 

exposure (food and drinking water). 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. Quinoxyfen is classified as “not likely to be 

carcinogenic to humans”; therefore, cancer aggregate risk assessments were not performed.

7.1 Acute Aggregate Risk

No toxic effects attributable to a single (i.e., acute) exposure to quinoxyfen have been identified; 

therefore, an acute aggregate risk assessment has not been conducted. 

7.2 Chronic Aggregate Risk

The chronic aggregate risk assessment takes into account average exposure estimates from 

dietary consumption of quinoxyfen (food and drinking water). The chronic dietary exposure 

estimates are not of concern to HED (<100% cPAD) for the general U.S. population and all 

population subgroups (see Table 5.4.6). The dietary exposure assessment assumed 100% CT, 

DEEM 7.81 default concentration factors, and tolerance-level residues for all commodities, and a 

Tier 1 chronic surface water EDWC generated by the FIRST model. 

 

2 Available: http://www.epa.gov/opp00001/factsheets/spraydrift.htm 
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8.0 Cumulative Exposure/Risk Characterization

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as 

to 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/.

9.0 Occupational Exposure/Risk Characterization

An occupational exposure assessment of the proposed uses was provided in a HED 

memorandum dated 01-AUG-2013 (Memo, J. Tyler; D410694). For the proposed use sites, 

there is a potential for short- and intermediate-term occupational exposure to quinoxyfen during 

mixing, loading, applying, and other handling tasks, as well as during post-application activities. 

There are no short-and intermediate-term dermal endpoints and PODs; therefore, quantitative 

dermal handler and post-application assessments were not conducted. Only inhalation handler 

exposure was assessed. Additionally, since the same endpoint and POD were selected for shortand intermediate-term inhalation durations, short-term inhalation exposure and risk estimates are 

considered to be protective of potential longer-term exposure and risk. Chronic exposure is not 

expected for the proposed agricultural uses.

9.1 Short- and Intermediate-Term Handler Risk

The scenarios assessed for occupational handlers include mixing/loading liquids to support 

aerial, airblast, and groundboom applications, applying sprays with aerial, airblast, and 

groundboom equipment, and flagging for liquid aerial applications. 

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 (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 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 Table3”, 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 website4.

Estimates of inhalation exposure were calculated for various levels of personal-protective 

equipment (PPE). Results are presented for “baseline,” defined as a single layer of clothing 

 

3 Available: http://www.epa.gov/opp00001/science/handler-exposure-table.pdf

4 Available: http://www.epa.gov/pesticides/science/handler-exposure-data.html
Quinoxyfen Human-Health Risk Assessment DP# 410691

Page 24 of 32

consisting of a long-sleeved shirt, long pants, shoes plus socks, no protective gloves, and no 

respirator, as well as baseline with various levels of PPE as necessary (e.g., gloves, respirator, 

etc). The proposed product label involved in this assessment directs applicators and other 

handlers to wear a long-sleeved shirt and long pants, socks, shoes, and chemical-resistant gloves 

made of waterproof material.

Table 9.1.1 provides a summary of the estimated inhalation exposures and risks to occupational 

pesticide handlers. An MOE ≥100 is adequate to protect occupational pesticide handlers from 

inhalation exposure. 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., longsleeved shirt, no respirator, 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 Agency matches quantitative occupational exposure assessment with appropriate 

characterization of exposure potential. While HED presents quantitative risk estimates for 

human flaggers where appropriate, agricultural aviation has changed dramatically over the past 

two decades. According to the 2012 National Agricultural Aviation Association (NAAA) survey 

of their membership, the use of Global Positioning System (GPS) for swath guidance in 

agricultural aviation has grown steadily from the mid 1990s. Over the same time period, the use 

of human flaggers for aerial pesticide applications has decreased steadily from ~15% in the late 

1990s to only 1% in the most recent (2012) NAAA survey. The Agency will continue to monitor 

all available information sources to best assess and characterize the exposure potential for human 

flaggers in agricultural aerial applications.

Table 9.1.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for Quinoxyfen. 

Exposure 

Scenario Crop or Target

Inhalation Unit 

Exposure

(μg/lb ai)1 Maximum 

Application 

Rate2

Area Treated 

or Amount 

Handled 

Daily3

Inhalation

Mitigation Level

Dose 

(mg/kg/day)4 MOE5

Mixer/Loader

Liquids – Aerial 

application Fruiting Vegetables (Group 8-

10B), Low Growing Berry 

(Subgroup 13-07G) Baseline: 0.219

0.098 lb ai/A

350 A 0.0000939 210,000

Liquids –

Groundboom 

applications

80 A 0.0000215 930,000

Liquids –

Airblast 

application

Small Fruit Vine Climbing 

Except Fuzzy Kiwifruit 

(Subgroup 13-07F)

0.11 lb ai/A 40 A 0.0000121 1,700,000

Applicator

Aerial 

applications Fruiting Vegetables (Group 8-

10B), Low Growing Berry 

(Subgroup 13-07G)

Eng. control: 

0.0049 0.098 lb ai/A

350 A 0.0000021 9,500,000

Groundboom 

applications Baseline: 0.34 80 A 0.0000344 600,000

Airblast 

applications

Small Fruit Vine Climbing 

Except Fuzzy Kiwifruit 

(Subgroup 13-07F)

Baseline: 4.71 0.11 lb ai/A 40 A 0.000259 77,000

Flagger

Flagger

Fruiting Vegetables (Group 8-

10B), Low Growing Berry 

(Subgroup 13-07G)

Baseline: 0.35 0.098 lb ai/A 350 A 0.00015 130,000
Quinoxyfen Human-Health Risk Assessment DP# 410691

Page 25 of 32

Table 9.1.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for Quinoxyfen. 

Exposure 

Scenario Crop or Target

Inhalation Unit 

Exposure

(μg/lb ai)1 Maximum 

Application 

Rate2

Area Treated 

or Amount 

Handled 

Daily3

Inhalation

Mitigation Level

Dose 

(mg/kg/day)4 MOE5

Mixer/loader/Applicator

Liquids –

Mechanicallypressurized 

handgun

Small Fruit Vine Climbing 

Except Fuzzy Kiwifruit 

(Subgroup 13-07F) Baseline: 3.9

0.0037 lb 

ai/gal 1,000 gal 0.00018 110,000

Fruiting Vegetables (Group 8-

10B), Low Growing Berry 

(Subgroup 13-07G)

0.0033 lb 

ai/gal 1,000 gal 0.000161 120,000

1

 Unit Exposures are taken from “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table,” September 2012. 

2

 Based on proposed Quintec®label (Reg. No. 62719-375).

3

 Units Treated are taken from “Standard Values for Daily Acres Treated in Agriculture”; ExpoSAC SOP No. 9.1, revised 25 

September 2001.

4

 Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/A or gal) × 

Area Treated or Amount Handled (A or gal/day) ÷ BW (80 kg).

5

 Inhalation MOE = Inhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day). Inhalation NOAEL = 20 mg/kg/day.

9.2 Short- and Intermediate-Term Post-Application Risk

HED uses the term post-application to describe exposures that occur when individuals are 

present in an environment that has been previously treated with a pesticide (also referred to as reentry exposure). Such exposures may occur when workers enter previously treated areas to 

perform job functions, including activities related to crop production, such as scouting for pests 

or harvesting. Post-application exposure levels vary over time and depend on such things as the 

type of activity, the nature of the crop or target that was treated, the type of pesticide application, 

and the chemical’s degradation properties. In addition, the timing of pesticide applications, 

relative to harvest activities, can greatly reduce the potential for post-application exposure.

9.2.1 Dermal Post-Application Risk

In the absence of a short- and intermediate-term dermal POD, a quantitative short- and 

intermediate-term dermal post-application exposure assessment was not conducted.

REI: Quinoxyfen is classified in Toxicity Category III for acute dermal and primary eye 

irritation. It is classified in Toxicity Category IV for acute oral, acute inhalation and primary 

skin irritation and classified as a dermal sensitizer. The WPS Interim REI of 12 hours is 

sufficient to protect workers.

9.2.2 Inhalation Post-Application Risk

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

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

inhalation toxicity (Toxicity Category IV) and the low proposed use rate (0.11 lb ai/A). 

However, there are multiple potential sources of post-application inhalation exposure to 

individuals performing post-application activities in previously treated fields. These potential 

sources include volatilization of pesticides and resuspension of dusts and/or particulates that 

contain pesticides. The Agency sought expert advice and input on issues related to volatilization 

of pesticides from its FIFRA SAP in December 2009, and received the SAP’s final report on 
Quinoxyfen Human-Health Risk Assessment DP# 410691

Page 26 of 32

March 2, 20105. The Agency is in the process of evaluating the SAP report as well as available 

post-application inhalation exposure data generated by the ARTF 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.

Although a quantitative occupational post-application inhalation exposure assessment was not 

performed, an inhalation exposure assessment was performed for occupational/commercial 

handlers. Handler exposure resulting from application of pesticides outdoors is likely to result in 

higher exposure than post-application exposure. Therefore, it is expected that these handler 

inhalation exposure estimates would be protective of most occupational post-application 

inhalation exposure scenarios.

10.0 References

Previous Risk Assessments: B. Hanson, 22-JAN-2009; D351021. G. Kramer, et al.; 15-MAY2006; D321331

HASPOC Memo: K. Rury, 20-MAR-2013; TXR# 0056609

Chemistry Memo: G. Kramer; 20-AUG-2013; D407728

Drinking Water Memo: K. Milians, 23-APR-2013; D407730

Dietary Memo: G. Kramer; 20-AUG-2013; D410693

Occupational Exposure Memo: J. Tyler; 01-AUG-2013; D410694

List of Appendices:

Appendix A. Toxicology Profile and Executive Summaries

Appendix B. Physical/Chemical Properties

Appendix C. Review of Human Research

cc: G. Kramer, M. Perron, J. Tyler

RDI: RAB1 (29-MAY-2013) 

G.F. Kramer:S10957:PY-S:(703)305-5079:7509P:RAB1

 

5 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html
Quinoxyfen Human-Health Risk Assessment DP# 410691

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Appendix A. Toxicology Profile and Executive Summaries

A.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 in Rodents ..................................

870.3150 90-Day Oral Toxicity in Nonrodents.............................

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 Human-Health Risk Assessment DP# 410691

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A.2 Toxicity Profiles

Table A.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.

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.
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Page 29 of 32

Table A.2. Subchronic, Chronic, and Other Toxicity Profile - Quinoxyfen.

Guideline No. Study Type

MRID No. (year)/ 

Classification /Doses Results

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.

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 fluorphenyl ring-hydroxy-XDE795 (unconjugated) in the feces. The major route of 

elimination was through urine in the phenyl-labeled 

quinoxyfen and through the feces in the quinolinelabeled quinoxyfen. 

Classified as non-guideline due to several 

unanalyzed fractions.
Quinoxyfen Human-Health Risk Assessment DP# 410691

Page 30 of 32

Table A.2. Subchronic, Chronic, and Other Toxicity Profile - Quinoxyfen.

Guideline No. Study Type

MRID No. (year)/ 

Classification /Doses Results

870.7800 Immunotoxicity 48106301 (2010)

Acceptable/guideline

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

NOAEL = 250 mg/kg/day.

LOAEL = not established. 
Quinoxyfen Human-Health Risk Assessment DP# 410691

Page 31 of 32

Appendix B. Physical/Chemical Properties

Table B.1. 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/cm3at 20 °C

Vapor pressure 1.2 x 10-5Pa 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.
Quinoxyfen Human-Health Risk Assessment DP# 410691

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Appendix C. Review of Human Research

This risk assessment relies in part on data from studies in which adult human subjects were 

intentionally exposed to a pesticide or other chemical. These data, which include studies from 

the PHED 1.1, the AHETF database, and the ARTF database are (1) subject to ethics review 

pursuant to 40 CFR 26, (2) have received that review, and (3) are compliant with applicable 

ethics requirements. For certain studies, the ethics review may have included review by the 

Human Studies Review Board. Descriptions of data sources, as well as guidance on their use, 

can be found at the Agency website6. 

 

6

http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

http://www.epa.gov/pesticides/science/post-app-exposure-data.html