Page 1 of 9 

### UNITED STA

**TES ENVIRONMENTA L PROTECTION A** **GENCY WA** **SHINGTON, D.C. 20460 OFFICE OF**  **CHEMICAL SAFETY AND POLLUTION PREVENTION**  

### MEMORANDUM **D ATE**  **:** 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:** D4 1 0 693 **Decision No.:** 471748 **Registration No. :**  62719 - 375 **Petition No.:** 2E8117 **Regulatory Action:** Sec. 3 Registration **Risk Assessment Type:** Dietary **Case No.:** 7037 **T XR 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 dieta ry - exposure and risk assessment w as conducted using the Dietary Exposure Evaluation Model - Food Consumption I ntake 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, (N HANES/WWEI A; 2003 - 2008). Thi s anal ys i s w as performed to support a proposed Section 3 Registration for applicationQuinoxyfen Dietary Exposure and Risk Assessment DP # 410693

______________________________ ________________________________________________________

Page 2 of 9 

### of quinox yf

en 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 b y 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 qu inoxyfen have been identified; therefore, an acute population - adjusted dose (aPAD) has not been established for quinox yf en and an acute dietary

exposure assessment has not been conducted. Chronic Dietary

(Food and Drinking Water) Exposure Results and Ch aracterization The unrefined chronic analy sis 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 directl y int o th e 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 gener al U.S. population and 8.5 % of the cPAD for the most highly

exposed population subgroup ( children 1 - 2 y ears 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 unreasona ble adverse health effects). This dose is referred to as the PAD. The PAD is equivalent to point of departure (POD, NOAEL, LOAE L, i.e. ) divided by the required uncertaint y and/ or safet y factors. For acute and non - cancer chronic exposures, HED is concern ed when estimated dietary risk exceeds 100% of the PAD. HED is generall y 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 w eb 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 , D 354561 ).Quinoxyfen Dietary Exposure and Risk Assessment DP # 410693

______________________________ ________________________________________________________

Page 3 of 9 

### II. **Residue Information** Quinoxyfen Proposed and Registered Uses: There is currentl y 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 vegetabl e, 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 onl y. Esta blished 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 ; D 407728 ): **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 **Rem ove from** **40 CFR §180.588 (a):**  Grape Pepper, bell Pepper, nonbell Straw berry 

### Residue Data used for Acute and Chronic Assessments: The unrefined chronic analy sis 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 - ye ar period, PDP anal yz ed 552 samples of catfish for quinoxyfen residues. None of the samples contained detectable residues. As a result, residues inQuinoxyfen Dietary Exposure and Risk Assessment DP # 410693

______________________________ ________________________________________________________

Page 4 of 9 

### fish were not included in the assessment. **III. Percent Crop Treated Information** The chronic assessment i s 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 directl y into the DEEM - FCID into the food categories “water, direct, all sources” and “water, indirect, all sources.” Screening EDWCs ( Table 2 ) for quinox yf en 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 i nterval of seven day s), 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 day s). Table 2 lists the EDWCs for surface water and ground water recommended for use in dietary

risk asse ssment. These EDWCs represent concentrations of quinoxyfen plus its degradate 3 - OH quinox yfen . **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 w as 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 day s. Foods “as con sumed” (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 publicl y 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 anal ys is of the 2003 - 2008 WWEIA consumption data, which took into account dietary patterns and survey respondent s, HED concluded that it is most appropriate to report risk for the following population subgroups: the general U.S. population, all infants (<1 ye ar old), children 1 - 2, children 3 - 5, children 6 - 12, youth 13 - 19, adults 20 - 49, females 13 - 49, and adults 50 - 9 9 y ears old.Quinoxyfen Dietary Exposure and Risk Assessment DP # 410693

______________________________ ________________________________________________________

Page 5 of 9 

### 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 dail y 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 expo sure. Exposure is expressed in mg/kg body weight/day and as a percent of the cPAD. This procedure is performed for each population subgroup. **V I**  **. Toxicological Information**  **Table 3. Summary of Toxicological Doses and Endpoints for Quinoxyfen for Use i**  **n Dietary Hum an**  **- Health**  **Risk Assessments** Exposure/ Scenario P O D Uncertainty/ FQPA SFs RfD, PAD, Level

of Concern for Risk Assessment Study and Toxicological Effects Ac ute Dietary (All Populations) Not

applicable Not applicable Not applicable No adverse effects attributable to a single dose were observed. As a result, no hazard w as identified and an endpoint was not selected to assess this exposure scenario. Chronic Dietary (All Populations) NOAEL=

20 mg/kg/day UF A = 10 X

UF H = 10 X FQPA SF= 1 X Chronic RfD =

0.2 mg/kg/day cPAD = 0.2 mg/kg/day Com bined 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 d eparture (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 adv erse - effect level. LOAEL = lowest - observed adverse - effect level. UF = uncertainty factor. UF A = 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. 

### V **I I.**  **Results/Discussion** For a chronic assessment, HED is concerned when dietary risk exceeds 100% of the PAD. The DEEM - FCID anal ys es 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 ye ar old), children 1 - 2 y ears old, children 3 - 5 y ears old, children 6 - 12 y ears old, yo uth 13 - 19 y ears old, females 13 - 49 y ears old, adults 20 - 49 y ears old, and adults 50+ y ears old. Results of Chronic Dietary Exposure Analy s i s 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 ye ars old , i s 8.5 % of the cPAD.Quinoxyfen Dietary Exposure and Risk Assessment DP # 410693

______________________________ ________________________________________________________

Page 6 of 9 

### The results of the chronic dietary e xposure anal ys i s is reported in Table 4 . **Table 4**  **. Summary of Dietary (Food and Drinking Water) Exposure Risk for Quinoxyfen**  **.** Population Subgroup Ac ute 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 y ears old N/A N/A **0.016903 8.5**  Children 3 - 5 y ears old N/A N/A 0.014353 7.2 Children 6 - 12 y ears old N/A N/A 0.007967 4.0 Youth 13 - 19 y ears old N/A N/A 0.005047 2. 5 Adults 20 - 49 y ears old N/A N/A 0.005882 2. 9 Adults 50 - 99 y ears old N/A N/A 0.005669 2. 8 Fem ales 13 - 49 y ears old N/A N/A 0.005907 3 .0 *The values for the highest exposed population for each type of risk assessment are bolded. 

### V **I II.**  **Characterization of Inputs/Outputs** Th i s 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 anal ys i s using DEEM - FCID indicates that dietary risk s 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 an y population subgroup. **X. List of**  **Attachments**

· Chronic Food plus Water Residue Input File.

· Chronic Results File.

cc: G. Kramer (RAB1) RDI: DESAC ( 5 / 8 / 1 3 ) G.F. Kramer:S10 95 7:PY - S:(703)305 - 5079:7509P:RAB1Quinoxyfen Dietary Exposure and Risk Assessment DP # 410693

______________________________ ________________________________________________________

Page 7 of 9 

### 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 Pr ogram 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 080223400 0 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, n onbell - 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 1.00 0 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, dr ied - 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, p rune, 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 1.000Quinoxyfen Dietary Exposure and Risk Assessment DP # 410693

______________________________ ________________________________________________________

Page 8 of 9 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 1.00 0 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 Straw berry 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 sourc es 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 9500178 000 O Grape, raisin 2.000000 4.300 1.000 9500188000 O Hop 3.000000 1.000 1.000Quinoxyfen Dietary Exposure and Risk Assessment DP # 410693

______________________________ ________________________________________________________

Page 9 of 9 

### Chronic Results File.

EPA Ver. 3.16, 03 - 08 - d D EEM - 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% Fema le 13 - 49 0.005907 3.0%

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