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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF

CHEMICAL SAFETY AND

POLLUTION PREVENTION

MEMORANDUM

DATE: 20-AUG-2013

SUBJECT: 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.

PC Code: 055459 DP Barcode: D410693

Decision No.: 471748 Registration No.: 62719-375

Petition No.: 2E8117 Regulatory Action: Sec. 3 Registration

Risk Assessment Type: Dietary Case No.: 7037

TXR No.: NA CAS No.: 124495-18-7

MRID No.: NA 40 CFR: 180.588

FROM: George F. Kramer, Ph.D., Senior Chemist

Risk Assessment Branch 1 (RAB1)/Health Effects Division (HED; 7509P)

THROUGH: David E. Hrdy, Senior Biologist

Seyed Tadayon, Chemist

Dietary Exposure Science Advisory Council (DESAC)

HED (7509P)

and

Dana M. Vogel, Acting Branch Chief, RAB1

Associate Division Director, HED (7509P)

TO: George F. Kramer, Ph.D., Risk Assessor

RAB1/HED (7509P)

and

Barbara Madden/Sidney Jackson, RM 05

Registration Division (RD) (7505P)

Executive Summary

A chronic dietary-exposure and risk assessment was conducted using the Dietary Exposure 

Evaluation Model - Food Consumption Intake Database (DEEM-FCID, ver. 3.16) which 

incorporates consumption data from United States Department of Agriculture (USDA) National 

Health and Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA; 2003-

2008). This analysis was performed to support a proposed Section 3 Registration for application 
Quinoxyfen Dietary Exposure and Risk Assessment DP# 410693

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of quinoxyfen to vegetable, fruiting, group 8-10; fruit, small vine climbing, except fuzzy

kiwifruit, subgroup 13-07F; and berry, low growing subgroup 13-07G. This memorandum was 

reviewed by two peer reviewers of the DESAC, per DESAC SOP 2012.1.

Acute Dietary (Food and Drinking Water) Exposure Results and Characterization

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

therefore, an acute population-adjusted dose (aPAD) has not been established for quinoxyfen and 

an acute dietary exposure assessment has not been conducted. 

Chronic Dietary (Food and Drinking Water) Exposure Results and Characterization

The unrefined chronic analysis assumed 100% crop treated (CT), DEEM 7.81 default 

concentration factors, and tolerance-level 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 FQPA Index Reservoir Screening Tool 

(FIRST) model. The chronic dietary risk estimates (food + water) were 2.4% of the chronic 

population-adjusted dose (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).

Cancer Dietary (Food and Drinking Water) Exposure Results and Characterization

Quinoxyfen is classified as “not likely carcinogenic to humans.” Therefore, cancer risk is not a 

concern for this chemical.

I. Introduction

Dietary risk assessment incorporates both exposure and toxicity of a given pesticide. For acute 

and chronic assessments, the risk is expressed as a percentage of a maximum acceptable dose 

(i.e., the dose which HED has concluded will result in no unreasonable adverse health effects). 

This dose is referred to as the PAD. The PAD is equivalent to point of departure (POD, 

NOAEL, LOAEL, i.e.) divided by the required uncertainty and/or safety factors.

For acute and non-cancer chronic exposures, HED is concerned when estimated dietary risk 

exceeds 100% of the PAD. HED is generally concerned when estimated cancer risk exceeds one 

in one million. References which discuss the acute and chronic risk assessments in more detail 

are available on the EPA/pesticides web site: “Available Information on Assessing Exposure 

from Pesticides, A User’s Guide,” 21-JUN-2000, web link: http://www.epa.gov/fedrgstr/EPAPEST/2000/July/Day-12/6061.pdf; or see SOP 99.6 (20-AUG-1999).

The most recent dietary exposure risk assessment for quinoxyfen was conducted by W. Carr

(Memo, 02-DEC-2008, D354561).
Quinoxyfen Dietary Exposure and Risk Assessment DP# 410693

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II. Residue Information

Quinoxyfen Proposed and Registered Uses:

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). The 

Interregional Project No. 4 (IR-4) has proposed a Section 3 Registration for application of 

quinoxyfen to vegetable, fruiting, group 8-10; fruit, small vine climbing, except fuzzy kiwifruit, 

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

Residues of Concern: 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.

Established Tolerances: 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, non-bell 

(1.7 ppm); strawberry (0.90 ppm); pumpkin (0.30 ppm); squash, winter (0.30 ppm); and melon 

subgroup 9A (0.08 ppm). 

Recommended Tolerances: Based on the residue chemistry data submitted with the current 

petition, HED recommended for establishment of the following tolerances (G. Kramer, 20-AUG2013; D407728):

Table 1. Tolerance Summary for Quinoxyfen. 

Commodity

Proposed 

Tolerance (ppm)

HED-Recommended 

Tolerance (ppm)

Correct Commodity 

Definition/Comments

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

Remove from 40 CFR §180.588 (a):

Grape

Pepper, bell

Pepper, nonbell

Strawberry

Residue Data used for Acute and Chronic Assessments:

The unrefined chronic analysis assumed tolerance-level residues for all commodities. 

Processing Factors: DEEM 7.81 default processing factors were used for all processed 

commodities (where provided).

Fish: The USDA Pesticide Data Program (PDP) monitored pesticide residues in catfish in 2008, 

2009, and 2010. Over this three-year period, PDP analyzed 552 samples of catfish for 

quinoxyfen residues. None of the samples contained detectable residues. As a result, residues in 
Quinoxyfen Dietary Exposure and Risk Assessment DP# 410693

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fish were not included in the assessment.

III. Percent Crop Treated Information

The chronic assessment is based on the assumption of 100% CT for all commodities.

IV. Drinking Water Data

The Estimated Drinking Water Concentrations (EDWCs) used in the dietary exposure risk 

assessment were provided by the Environmental Fate and Effects Division (EFED) in a 

memorandum dated 4/23/13 (Memo, K. Milians; DP# 407730). Water residues were 

incorporated directly into the DEEM-FCID into the food categories “water, direct, all sources” 

and “water, indirect, all sources.”

Screening EDWCs (Table 2) for quinoxyfen were generated with were estimated using the 

FIRST model for surface water and the Screening Concentration in Ground Water (SCI-GROW)

model for groundwater. EDWCs were determined based on an annual application rate of 0.57 lb 

a.i./A (five applications at 0.114 lb a.i./A, with a re-application interval of seven days), and an 

annual application rate of 0.52 lb a.i./A (four applications at 0.13 lb a.i./A, with a re-application 

interval of six days). Table 2 lists the EDWCs for surface water and ground water recommended 

for use in dietary risk assessment. These EDWCs represent concentrations of quinoxyfen plus its 

degradate 3-OH quinoxyfen.

Table 2. Tiered EDWCs for Proposed Quinoxyfen Uses.

Source (Tier: Model)

1-in-10-year Peak Exposure 

(ppb)

1-in-10-year Annual Mean 

Exposure (ppb)

Surface water (Tier I: FIRST) 9.9 0.66

(used in chronic analysis)

Ground water (Tier I: SCI-GROW) 3.4 x 10-33.4 x 10-3

V. DEEM-FCID Program and Consumption Information

A quinoxyfen chronic dietary exposure assessment was conducted using the DEEM-FCID

model, Version 3.16, which incorporates 2003-2008 consumption data from USDA’s 

NHANES/WWEIA. The data are based on the reported consumption of more than 20,000 

individuals over two non-consecutive survey days. Foods “as consumed” (e.g., apple pie) are 

linked to EPA-defined food commodities (e.g., apples, peeled fruit - cooked; fresh or N/S; baked; 

or wheat flour - cooked; fresh or N/S, baked) using publicly available recipe translation files 

developed jointly by USDA/ARS and EPA. For chronic exposure assessment, consumption data 

are averaged for the entire U.S. population and within population subgroups. Based on analysis 

of the 2003-2008 WWEIA consumption data, which took into account dietary patterns and 

survey respondents, HED concluded that it is most appropriate to report risk for the following 

population subgroups: the general U.S. population, all infants (<1 year old), children 1-2, 

children 3-5, children 6-12, youth 13-19, adults 20-49, females 13-49, and adults 50-99 years 

old.
Quinoxyfen Dietary Exposure and Risk Assessment DP# 410693

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For a chronic dietary exposure assessment, an estimate of the residue level in each food or foodform (e.g., orange or orange juice) on the food commodity residue list is multiplied by the 

average daily consumption estimate for that food/food form to produce a residue intake estimate. 

The resulting residue intake estimate for each food/food form is summed with the residue intake 

estimates for all other food/food forms on the commodity residue list to arrive at the total 

average estimated exposure. Exposure is expressed in mg/kg body weight/day and as a percent 

of the cPAD. This procedure is performed for each population subgroup.

VI. Toxicological Information

Table 3. Summary of Toxicological Doses and Endpoints for Quinoxyfen for Use in Dietary Human-Health 

Risk Assessments

Exposure/ 

Scenario POD

Uncertainty/

FQPA SFs

RfD, PAD, Level 

of Concern 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 (rats)

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.

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. UFA = extrapolation from animal to human (interspecies). FQPA SF = FQPA Safety Factor. 

PAD = population-adjusted dose (a = acute, c = chronic). RfD = reference dose. LOC = level of concern.

VII. Results/Discussion 

For a chronic assessment, HED is concerned when dietary risk exceeds 100% of the PAD. The 

DEEM-FCID analyses estimate the dietary exposure of the U.S. population and various 

population subgroups. The results reported in Table 5 are for the general U.S. population, all 

infants (<1 year old), children 1-2 years old, children 3-5 years old, children 6-12 years old, 

youth 13-19 years old, females 13-49 years old, adults 20-49 years old, and adults 50+ years old. 

Results of Chronic Dietary Exposure Analysis

The chronic dietary risk for food and drinking water utilized 3.3% of the cPAD for the U.S. 

population. The chronic dietary risk for the highest exposed population subgroup, children 1-2 

years old, is 8.5% of the cPAD. 
Quinoxyfen Dietary Exposure and Risk Assessment DP# 410693

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The results of the chronic dietary exposure analysis is reported in Table 4. 

Table 4. 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.

VIII. Characterization of Inputs/Outputs

This chronic dietary exposure and risk estimate is conservative since it assumed 100% CT, 

DEEM 7.81 default concentration factors, and tolerance-level and were based on screening level 

estimates of drinking water concentrations generated by the FIRST model. They could be 

further refined through the use of anticipated residues, empirical processing factors and % CT 

data, as well as refined drinking water estimates.

IX. Conclusions

The chronic dietary exposure and risk analysis using DEEM-FCID indicates that dietary risks to 

quinoxyfen from food and drinking water are well below HED’s levels of concern for this 

pesticide. Estimated chronic dietary risks are ≤8.5% of the cPAD for the general U.S. population 

and all population subgroups. HED is confident that the assessment does not underestimate risk 

to the general U.S. population or any population subgroup. 

X. List of Attachments

· Chronic Food plus Water Residue Input File.

· Chronic Results File.

cc: G. Kramer (RAB1)

RDI: DESAC (5/8/13)

G.F. Kramer:S10957:PY-S:(703)305-5079:7509P:RAB1
Quinoxyfen Dietary Exposure and Risk Assessment DP# 410693

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Chronic Food plus Water Residue Input File.

Filename: C:\Documents and Settings\gkramer\My Documents\Gk\##Quinoxyfen\QUINOXYFEN.R08

Chemical: Qunioxyfen

RfD(Chronic): .2 mg/kg bw/day NOEL(Chronic): 0 mg/kg bw/day

RfD(Acute): 0 mg/kg bw/day NOEL(Acute): 0 mg/kg bw/day

Date created/last modified: 05-09-2013/13:21:01 Program ver. 3.16, 03-08-d

Comment: Chronic dietary assessment to support new uses on lettuce, strawberry, pepper & 

melons.

-----------------------------------------------------------------------------------

 EPA Crop Def Res Adj.Factors Comment

 Code Grp Commodity Name (ppm) #1 #2 

---------- ---- ------------------------------- ---------- ------ ------ -------

0401204000 4A Lettuce, head 7.000000 1.000 1.000 

0401205000 4A Lettuce, leaf 19.000000 1.000 1.000 

0801374000 8A Tomatillo 1.700000 1.000 1.000 

0801375000 8A Tomato 1.700000 1.000 1.000 

0801375001 8A Tomato-babyfood 1.700000 1.000 1.000 

0801376000 8A Tomato, paste 1.700000 5.400 1.000 

0801376001 8A Tomato, paste-babyfood 1.700000 5.400 1.000 

0801377000 8A Tomato, puree 1.700000 3.300 1.000 

0801377001 8A Tomato, puree-babyfood 1.700000 3.300 1.000 

0801378000 8A Tomato, dried 1.700000 14.300 1.000 

0801378001 8A Tomato, dried-babyfood 1.700000 14.300 1.000 

0801379000 8A Tomato, juice 1.700000 1.500 1.000 

0801380000 8A Tomato, Tree 1.700000 1.000 1.000 

0802148000 8BC Eggplant 1.700000 1.000 1.000 

0802234000 8BC Okra 1.700000 1.000 1.000 

0802270000 8B Pepper, bell 1.700000 1.000 1.000 

0802270001 8B Pepper, bell-babyfood 1.700000 1.000 1.000 

0802271000 8B Pepper, bell, dried 1.700000 1.000 1.000 

0802271001 8B Pepper, bell, dried-babyfood 1.700000 1.000 1.000 

0802272000 8BC Pepper, nonbell 1.700000 1.000 1.000 

0802272001 8BC Pepper, nonbell-babyfood 1.700000 1.000 1.000 

0802273000 8BC Pepper, nonbell, dried 1.700000 1.000 1.000 

0901075000 9A Cantaloupe 0.080000 1.000 1.000 

0901187000 9A Honeydew melon 0.080000 1.000 1.000 

0901399000 9A Watermelon 0.080000 1.000 1.000 

0901400000 9A Watermelon, juice 0.080000 1.000 1.000 

0902308000 9B Pumpkin 0.200000 1.000 1.000 

0902309000 9B Pumpkin, seed 0.200000 1.000 1.000 

0902357000 9B Squash, winter 0.200000 1.000 1.000 

0902357001 9B Squash, winter-babyfood 0.200000 1.000 1.000 

1201090000 12A Cherry 0.700000 1.000 1.000 

1201090001 12A Cherry-babyfood 0.700000 1.000 1.000 

1201091000 12A Cherry, juice 0.700000 1.500 1.000 

1201091001 12A Cherry, juice-babyfood 0.700000 1.500 1.000 

1202012000 12B Apricot 0.700000 1.000 1.000 

1202012001 12B Apricot-babyfood 0.700000 1.000 1.000 

1202013000 12B Apricot, dried 0.700000 6.000 1.000 

1202014000 12B Apricot, juice 0.700000 1.000 1.000 

1202014001 12B Apricot, juice-babyfood 0.700000 1.000 1.000 

1202230000 12B Nectarine 0.700000 1.000 1.000 

1202260000 12B Peach 0.700000 1.000 1.000 

1202260001 12B Peach-babyfood 0.700000 1.000 1.000 

1202261000 12B Peach, dried 0.700000 7.000 1.000 

1202261001 12B Peach, dried-babyfood 0.700000 7.000 1.000 

1202262000 12B Peach, juice 0.700000 1.000 1.000 

1202262001 12B Peach, juice-babyfood 0.700000 1.000 1.000 

1203285000 12C Plum 0.700000 1.000 1.000 

1203285001 12C Plum-babyfood 0.700000 1.000 1.000 

1203286000 12C Plum, prune, fresh 0.700000 1.000 1.000 

1203286001 12C Plum, prune, fresh-babyfood 0.700000 1.000 1.000 

1203287000 12C Plum, prune, dried 0.700000 5.000 1.000 

1203287001 12C Plum, prune, dried-babyfood 0.700000 5.000 1.000 

1203288000 12C Plum, prune, juice 0.700000 1.400 1.000 

1203288001 12C Plum, prune, juice-babyfood 0.700000 1.400 1.000 

1304175000 13D Grape 2.000000 1.000 1.000 

1304176000 13D Grape, juice 2.000000 1.200 1.000 

1304176001 13D Grape, juice-babyfood 2.000000 1.200 1.000 
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1304179000 13D Grape, wine and sherry 2.000000 1.200 1.000 

1307130000 13G Cranberry 1.000000 1.000 1.000 

1307130001 13G Cranberry-babyfood 1.000000 1.000 1.000 

1307131000 13G Cranberry, dried 1.000000 1.000 1.000 

1307132000 13G Cranberry, juice 1.000000 1.100 1.000 

1307132001 13G Cranberry, juice-babyfood 1.000000 1.100 1.000 

1307359000 13G Strawberry 1.000000 1.000 1.000 

1307359001 13G Strawberry-babyfood 1.000000 1.000 1.000 

1307360000 13G Strawberry, juice 1.000000 1.000 1.000 

1307360001 13G Strawberry, juice-babyfood 1.000000 1.000 1.000 

8601000000 86A Water, direct, all sources 0.000660 1.000 1.000 EFED M

 Full comment: EFED Memo of April 23, 2013

8602000000 86B Water, indirect, all sources 0.000660 1.000 1.000 EFED M

 Full comment: EFED Memo of April 23, 2013

9500016000 O Artichoke, globe 1.400000 1.000 1.000 

9500177000 O Grape, leaves 2.000000 1.000 1.000 

9500178000 O Grape, raisin 2.000000 4.300 1.000 

9500188000 O Hop 3.000000 1.000 1.000 
Quinoxyfen Dietary Exposure and Risk Assessment DP# 410693

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Chronic Results File.

EPA Ver. 3.16, 03-08-d

DEEM-FCID Chronic analysis for QUNIOXYFEN NHANES 2003-2008 2-day

Residue file name: C:\Documents and Settings\gkramer\My 

Documents\Gk\##Quinoxyfen\QUINOXYFEN.R08

 Adjustment factor #2 used.

Analysis Date 05-10-2013/13:03:36 Residue file dated: 05-10-2013/13:03:15

Reference dose (RfD, Chronic) = .2 mg/kg bw/day

COMMENT 1: Chronic dietary assessment to support new uses on lettuce, strawberry, pepper & 

melons.

===============================================================================

 Total exposure by population subgroup

-------------------------------------------------------------------------------

 Total Exposure

 -----------------------------------

 Population mg/kg Percent of 

 Subgroup body wt/day Rfd 

-------------------------------------- ------------- ----------------

Total US Population 0.006582 3.3%

Hispanic 0.006634 3.3%

Non-Hisp-White 0.006838 3.4%

Non-Hisp-Black 0.005438 2.7%

Non-Hisp-Other 0.005736 2.9%

Nursing Infants 0.002600 1.3%

Non-Nursing Infants 0.006942 3.5%

Female 13+ PREG 0.005848 2.9%

Children 1-6 0.014843 7.4%

Children 7-12 0.007292 3.6%

Male 13-19 0.005028 2.5%

Female 13-19/NP 0.005066 2.5%

Male 20+ 0.005508 2.8%

Female 20+/NP 0.006050 3.0%

Seniors 55+ 0.005666 2.8%

All Infants 0.005601 2.8%

Female 13-50 0.005898 2.9%

Children 1-2 0.016903 8.5%

Children 3-5 0.014353 7.2%

Children 6-12 0.007967 4.0%

Youth 13-19 0.005047 2.5%

Adults 20-49 0.005882 2.9%

Adults 50-99 0.005669 2.8%

Female 13-49 0.005907 3.0%

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