
                 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 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/EPA-PEST/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).


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[(R)], 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-AUG-2013; 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 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[-3]
                                 3.4 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.

For a chronic dietary exposure assessment, an estimate of the residue level in each food or food-form (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.  

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 (95[th] 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

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  
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  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%

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