### 2 potential risks associated with the use of quinoxyfen as well as uncertainties unique to the risk assessment. This document also identifies additional studies that would be beneficial to the conduct of the ecological risk assessment. Below is a summary of data needs and uncertainties.

• Based on the environmental fate properties of quinoxyfen, exposure of sediment

- dwelling organisms is expected. Therefore, toxicity data on the standard set of benthic invertebrates are neede d

.

• For estuarine/marine invertebrates, the potential for chronic risk concerns is uncertain because a no

- observed

- adverse

- effects concentration (NOAEC) was not established ( i.e.
, adverse effects were observed at all concentrations tested) during a life

- cyc le toxicity study with mysid shrimp ( Americamysis bahia ); therefore, additional chronic toxicity data on this species are needed

.

• There is uncertainty regarding the potential effects of quinoxyfen on larval (brood) development of honey bees ( Apis mellifera ) and other terrestrial invertebrates, since acute toxicity data are only available for young adult honey bees but not for developing brood. EFED is now recommending that a larval toxicity test be performed as part of the new
t ier ed screening approach for assessing risk to bees.

2. Introduction



### Quinoxyfen is a systemic fungicide and belongs to the phenoxyquinoline class of chemicals. Quinoxyfen’s fungicidal activity is reported to be specific to powdery mildews ( e.g., Erysiphe cichoracearum, Sphaerothecafulg inea, Podosphaera clandestina ) (USEPA, 2003b). Based on information provided by the registrant, quinoxyfen appears to work with a novel mode of action which has attributes of a multi

- site fungicide and which differs from that of either of the two primary c lasses of synthetic, single

- site fungicides (demethylation inhibitors and strobilurins). The chemical’s main mode of action occurs at the cellular level and is through inhibition of primary appressorial formation (USEPA, 2003 b ; Wheeler et al . 2003). Quinox yfen is formulated as emulsifiable and suspension concentrates and it is used as a ground and/or aerial spray application. The m aximum single application rate f or quinoxyfen is on stone fruits at 0.130 pounds of active ingredient per acre ( lbs a.i./A )

. EFED evaluated the most recent ecological risk assessments for quinoxyfen in association with updated toxicity, exposure, and usage information to determine if sufficient data are available and if additional data are needed to support registration review. Recent risk assessments include a 2012 assessment for the use of quinoxyfen on fruiting vegetables group 8

- 10B, small fruit vine climbing (except fuzzy kiwifruit) subgroup 13

- 07F and low

- growing berry subgroup 13

- 07G ( USEPA

, 2013 c )

. In addition, EFED cons idered the latest Agency science policies and risk assessment methodologies.

3. Use Characterization



### Quinoxyfen is used as a ground (stone fruits, cherry, grape and hops) a nd/or aerial spray application (artichoke, head and leaf lettuce, melons, pepper, strawberry, gourds and pumpkin and winter squash). I t is currently registered for use on artichoke, gourds, lettuce, melons,

### 3 pepper, pumpkin, stone fruits, strawberry, winter squash, cherry, grapes and hops. The current maximum single application rate is 0 .1 30 lbs a.i./A for stone fruits and the maximum annual application is 0.57 lbs a.i./A for cherries. During the 2007

- 2011 timeframe, on average approximately 33,000 pounds of quinoxyfen were applied in the U.S. annually to treat 372,000 acres at an overall average application rate of 0.1 lbs. a.i./acre (USEPA 2013d). The top crops in terms of lbs a.i. applied during this period were wine grapes (52%), cherries (14%), table grapes (10%), raisin grapes (8%), stra wberries (5%), peppers (3%), watermelons (3%), and cantaloupes (2%). The top crops in terms of total area treated were wine grapes (54%), cherries (12%), table grapes (11%), raisin grapes (8%), and strawberries (5%) Further details on the quinoxyfen usage profile and history, based partially upon proprietary data sources, are provided in the BEAD Chemical Profile (USEPA 2013d ).

The chemical profile produced by BEAD, lists the use patterns of maximum exposures for the current uses of quinoxyfen. EFED will use application scenarios that result in maximum exposure scenarios for a given use for the risk assessment.

4. Conclusions from Previous Risk Assessments



### The Agency has conducted multiple ecological risk assessments on quinoxyfen that serve as a basis fo r this problem formulation, including a reduced risk assessment (USEPA 2013c). The major conclusions and uncertainties described in previous risk assessments of quinoxyfen are bulleted below and are summarized in Table 1 :

• There is the potential for advers e effects to Federally

- listed threatened/endangered (hereafter referred to as “listed”) and non

- listed mammals and estuarine/marine invertebrates on a chronic exposure basis.

• For estuarine/marine invertebrates, the potential for chronic risk is uncertain because a definitive no

- observed

- adverse

- effects concentration (NOAEC) was not established ( i.e.
, adverse effects were observed at all concentrations tested) during a life

- cycle toxicity study with mysid shrimp

.

• There is uncertainty regarding the potential effects of quinoxyfen on larval development of honey bees and other terrestrial invertebrates, since acute toxicity data are only available for young adult honey bees but not for developing brood.

• Quinoxyfen is expected to bioaccumulate in the aquatic environment based on available environmental fate and bioconcentration studies. However, due to the low application rates and low mobility of quinoxyfen, previous risk estimates for birds or mammals that feed on aquatic prey contaminated with quinoxyfen w ere below Agency acute and chronic risk levels of concern (LOCs)

.

• Quinoxyfen is likely to persist in the terrestrial environment (half

- lives of >102 days), but may be less persistent in the aquatic environment given that its anaerobic aquatic and aerobic a quatic metabolism half

- lives ranged from 18 to 50 days (slightly to moderate ly persistent).

• In drinking water, quinoxyfen plus its degradate 2

- oxo

- quinoxyfen, are considered to be of human health concern due to its structural similarity to the parent. How ever, only quinoxyfen is currently considered to be of ecological concern since major degradates

### 4 DCHQ and 2

- oxo

- quinoxyfen are considerably less toxic than the parent compounds to ecological receptors

.

a. Ecological Risk Assessment



### The Agency has conducted multiple ecological risk assessments o f quinoxyfen that serve as a basis for this scoping document, including a recent reduced risk assessment (USEPA 2013 a ) and recent new use ecological risk assessment (USEPA 2013c)

. The primary risk issues that have been identified have been for mammals on a chronic exposure basis . However, chronic risk has also been presumed for estuarine/marine invertebrates due to lack of definitive chronic toxicity data based on submitted studies

. Potential risk issues identified in previous assess m ents are briefly summarized in Table 1

.

Table 1 . Summary of Potential Risk Issues Identified for Quinoxyfen in Previous Assessments

Birds Mammals Terr. Plants Terr. Inverts Fish BCF Aquatic Inverts Aquatic Plants Groundwater Contamination Persistence Degradates of Concern

No Yes (chronic) No NA No Yes a Yes b (chronic) Yes c No Yes d No

Yes = at least one LOC has been exceeded in previous assessments; No = LOCs have not been exceeded in previous assessments; NA = RQs have not been calculated previously.

a The BCF threshold was passed (above 5000X) however, the risk to bids and mammals that feed on contaminated food item is below LOCs.
b Chronic risk to estuarine/marine invertebrates was assumed in previous risk assessments due to lack of definitive chronic toxicity data for mysid shrimp.

c Risk to aquatic plants was assumed in previous risk assessments due to lack of toxicity data on aquatic vascular plants; however, the most recent ecological r isk assessment (EPA 2013c) did not find any risks of concern for aquatic plants based on recently submitted vascular aquatic plant toxicity data for Lemna gibba (MRID 48387901)
d Not likely to persist in aquatic environment. However, i n terrestrial environ ments, q uinoxyfen is likely to persist, with half

- lives of >102 days

.

**b. Drinking Water Exposure Assessments** 



### The EFED conducted a drinking water assessment of quinoxyfen on April 23, 2013 (USEPA 2013 b and USEPA 2008). The estimated drinking water concentrations (EDWCs) recommended for use in the ( human ) Health Effects Division ’s dietary risk assessment were based on the cherr y use (highest EDWCs of the agricultural uses). The acute and chronic EDWCs f or surface water were 9.9 and 0.6 6 μg a.i./L (parts per billion; ppb), respectively and 0.00 3 μg a.i./L for groundwater. EDWCs represent concentrations of quinoxyfen plus its degradate 3

- OH quinoxyfen (hereafter 2

- oxo

- quinoxyfen; USEPA 2010 ) , which is con sidered to be of human health concern due to its structural simi larity to the parent (USEPA 2003a ).

**c. Clean Water Act Programs** 



### Quinoxyfen is not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean W ater Act. No Total Maximum Daily Load (TMDL) criteria have been developed for quinoxyfen

. 1

1 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885

### 5 5. Environmental Fate and Transport



### Quinoxyfen is likely to persist in the terrestrial environment (half

- lives of > 102 days), but may be less persistent in the aquatic environment given that its anaerobic aquatic and aerobic aquatic metabolism half

- lives ranged from 18 to 50 days (slightly to moderately persistent based on Goring et al. 1975). Quinoxyfen is expected to be relatively immobile in the environment, and is expected to readily partition to sediment (K oc 

### =18339

- 75930 mL/g, FAO scale, 2000). Because of its propensity to sorb to sediment and its generally low solubility, quinoxyfen has low potential to leach to g roundwater. However, quinoxyfen can reach surface waters through spray drift and runoff of sediment

- bound residues ( i.e ., erosion). Despite its overall persistence, under ideal conditions ( e.g. when the compound is present in an unsorbed state in clear, sh allow surface water under favorable light conditions) the compound may rapidly photodegrade (t 1/2 

### <1 day). However, such photodegradation can only happen under particular conditions that are not likely to occur in most circumstances. A selection of environm ental fate and transport properties of quinoxyfen is summarized Table 2

. Based on its vapor pressure (1.5x 10 - 7 

### atm) quinoxyfen is not expected to vol atilize. The chemical’s solubility in water exhibits pH dependence, with for example, the chemical being about three times more soluble at acidic than at neutral pHs (0.128 mg/L at pH 5, 0.047 mg/L at pH 7 and 0.036 mg/L at pH 9). The variable solubility i n water across pH values indicates that the compound exhibits acid

- base behavior.

Table 2

. Chemical Properties and Environmental Fate Parameters of Quinoxyfen
Parameter Value Description Reference
Chemical Classification phenoxyquinoline

Product Chemistry Molecular Formula C 15 H 8 Cl 2 FNO

PC Code 055459
Chemical Name (IUPAC) 5,7

- dichloro

- 4

- ( p

fluorophenoxy)quinoline Chemical Name (CAS) 5,7

- dichloro

- 4

- (4

- fluorophenoxy)quinoline
CAS Number 124495

- 18

- 7
Pesticide Classification Fungicide

Physical/ chemical property data Molecular Weight 308.14 g/mol

Water Solubility at 20 o C (ppm) 0.116, distilled water 0.128, pH 5 buffer 0.047, pH 7 buffer 0.036, pH 9 buffer Low solubility at pH 7

Vapor pressure (25 o C) 1.5 x 10 - 7 torr Should exist in both vapor and particulate phases

### 6 Parameter Value Description Reference

Henry's Law Constant at pH 7 1.29 x10 - 6 atm· m 3 ·mole - 1 (Calculated) Not likely to volatilize from water or wet surfaces Log Octanol/Water Partition coefficient (log K ow ) 4.66 Hydrophobic

potential to bioaccumulate 45360712

Persistence

Hydrolysis At 50°C quinoxyfen wa s stable at pH s 7 and 9

, over a 21 day study period. A half

- life of 6.35 days was measured at pH 4. Stable at neutral to alkaline pH MRID 45360620

Direct photolysis in water at pH 7 t 1/2 = < 1 day (observed half

- life). Quinoxyfen was detected only at day 1, at 0.76% of the applied amount in buffer solution. CFBPQ (2

- chloro

- 10

- fluoro[l]benzopyrano[2,3,4

- de ]quinoline) was found as degradate with t 1/2 = 1.2 day

. Non

- persistent MRID 45360623

The aqueous photo

- transformation of

dual 14 C quinoxyfen was studied at 25°C in sterile aqueous pH 5 (acetate) buffer solutions.
t 1/2 = 10.81 minutes MRID 45360624

Photolysis on soil t 1/2 = 74 days degradate 5,7

- dichloroquinoline

- 4

- 01 (DCHQ) was present at small amounts (<10% AR) Moderately persistent MRID 45360625

Aerobic soil metabolism t 1/2 = 495 days (sandy clay loam), 433 days (clay loam), 210 days (loamy sand), 577 days (sandy loam) Moderately persistent to persistent MRIDs 45360626, 45360627
t 1/2 = 102 days (sandy loam ), 315 days

(loam), 110 days (sandy loam), 257 days (loam) MRID 45360628

Anaerobic soil

metabolism t 1/2 = 289 days Persistent MRID 45360711 Anaerobic Aquatic metabolism t 1/2 = 18 days Slightly persistent MRID 45360629 Aerobic aquatic

metabolism t 1/2 = 50 days in aerobic flooded sandy loam soil Moderately persistent MRID 45360630 Field Dissipation

Terrestrial field dissipation t 1/2 = 94 days (sandy loam, CA) Moderately persistent MRID 45360704

t 1/2 = 65 days (loam, Ontario Canada) MRID 45360705

### 7 Parameter Value Description Reference

Half

- life not determined (sandy clay loam, Ile de France) Half

- life not determined (loamy silt Germany) Half

- life not determined (sandy clay loam, Oxfordshire England) The half

- life was not determined due to inadequate sampling

intervals; only 2

- 3 samples were collected each year of the study. MRIDs 453607

- 08,

- 09,

- 10

Mobility

Leaching and absorption/desorption K oc and K d in mL/g 21,550 and 366, sandy clay loam 18,339 and 385

, loamy sand 28,897 and 433, loamy sand H ardly mobile MRID 45360701

53,401 and 252

, loam 61,523 and 146, loam 45,287 and 73

, sand 75,178 and 1,803, loam

75,930 and 311, clay MRID 45360703

Fish Bioconcentration

Bioconcentration in fish (BCF) 5040X High BCF MRID 45360425 9101 X (fish) 26,705 X (green algae)* 18,865 X (waterfleas)* MRID 48488501
AR=Applied Radioactivity Classification of persistency was based on Goring scale, 1975. Mobility was described using FAO, 2000. *BCF may reflect sorption to surfaces of test organisms.



### Quinoxyfen has a high potential to bioconcentrate (BCF range: 5040

- 9101x) in fish tissue where it is not extensively metabolized. However, in one study quinoxyfen depurated rapidly when exposure to the compound wa s halted ( half

- life =2.7 d, MRID 45360425) and in anoth er study depuration was relatively slow (observed half

- life ~22 d, MRID 48488501).

Finally, two non

- guideline studies (MRID: 48488501) were submitted to measure the bioconcentration factor in the nonvascular aquatic green alga ( Pseudokirchneriella subcap itata ) and the freshwater invertebrate waterflea ( Daphnia magna ). The bioconcentration factors reported for these species at steady state were 26,705x (in algae) and 18,865x (in waterfleas), with depuration half

- lives of 13.2 hours and 10.6 hours, respecti vely.

The calculated BCF values in invertebrates and algae may also reflect sorption of the chemical to test surfaces of the organisms, as opposed to bioconcentration per se (SCHER, 2011). The high K oc 

### and K ow 

### of quinoxyfen suggest that the compound will partition to benthic sediments and/or move into the benthos through run

- off of sediment

- bound residues and may represent a potential source for quinoxyfen to enter aquatic food chains where it may bioconcentrat e/bioaccumulate.

### 8 In two terrestrial field dissipation studies

, dissipation half

- lives (DT 50 

### ) ranged from 65 to 94 days in loam and sandy loam, respectively. Additionally, three dissipation studies were conducted with sandy clay loam soils and loamy silt; however, half

- lives could not be derived due to inadequate sampling intervals (only 2

- 3 sampling intervals were collected per year). Although
t hese latter three did not provide definitive DT50 values, the studies lasted 5 years and quinoxyfen was detected throughout the study period, indicating that quinoxyfen is likely to persist in soil.

**a. Transformation Products** 



### The predomina nt degradates of quinoxyfen are: 2

- oxo

- quinoxyfen (USEPA 2010) ; 5, 7

- dichloroquinolin

- 4

- ol (DCHQ), 2

- chloro

- 10

- fluoro[l]benzopyrano[ 2,3,4

- delquinoline (CFBPQ), and 5,7

- dichloro

- 4

- methoxyquinoline ( DCMQ). Table 3 summarizes the transformation products of quinoxyfen and their maximum amounts formed for the respective environmental fate studies in which they were detected

. The transformation product DCHQ was identified as a major degradate in the hydrolysis study (higher than 10% of the applied radioactivity, AR) and accounted for 85, 3.20 and 0.99% of applied radioactivity (AR) at pH 4, 7, and 9, respectively at 21 days. Si milarly, this degradate was present at up to 17% AR in an aerobic soil metabolism study.

In photolysis in water (MRID 453606

- 24), CFBPQ accounted for 91.4% of the applied radioactivity at 1 hour a nd declined to 0.1% by 7 days. Numerous minor transformatio n products (<10% AR) were isolated but not all were identified

. Another major degradate is 2

- oxo

- quinoxyfen (formerly referred to as 3

- OH quinoxyfen , USEPA 2010 ) which was present in high amounts (>10% AR) in aerobic and anaerobic soil and aquatic metabo lism studies.

Lastly, DCMQ was detected in aerobic soil metabolism study but only at lower amounts (<10%AR)

.

### 9 Table 3

. Quinoxyfen and Its Major Environmental Degradates
Code Name/ Synonym Chemical Name Chemical Structure Study Type Ref. (MRID) Maximum %AR (day) Final %AR (study length)

PARENT

Quinoxyfen CAS No.: 124495

- 18

- 7

Formula: C 15 H 8 Cl 2 NFO MW: 308.14 g/mol Smile string: c1c(Cl)cc2nccc(Oc3ccc(F)c c3)c2c1Cl

TRANSFORMATION PRODUCTS

2

- oxo - quinoxyfen*

5,7

- dichloro

- 4

- (4

- fluorophenoxy)

- 2

-

(1H)

- quinolone Formula: C 15 H 8 Cl 2 NFO 2 MW: 324.14 g/mol Smile string: C1(=CC(=CC2=C1C(=CC( N2[H])=O)OC3=CC=C(C= C3)F)Cl)Cl Aerobic soil metabolism 45360628 sandy loam 61 (365) 62 (365) sandy loam 61 (365) 59.4 (365)
loam 18.9 (365) 14.5 (365) loam 18.9 (365) 14.5 (365)

Anaerobic soil

metabolism 45360711 Sand 9.13 (32) Sand 6.0 (100)
Anaerobic

aquatic metabolism 45360629 Sediment 83.2 (378) Sediment 83.2 (378)

Aerobic aquatic metabolism 45360630 40.6 (48) 33.5 (100)

Terrestrial field dissipation 45360704 0

- 15 cm 4.9 (122) 0

- 15 cm <4.9 (519)
45360705 0

- 15 cm 0

- 15 cm

### 10 Code Name/ Synonym Chemical Name Chemical Structure Study Type Ref. (MRID) Maximum %AR (day) Final %AR (study length) 2.5 (372) <LOD (489)

DCHQ

5,7

- dichloroquinolin

4

- ol CAS No.: 171850

- 29

- 6

Formula: C 9 H 5 Cl 2 NO MW: 214.05 g/mol Smile string: C1(=CC(=CC2=C1C(=CC= N2)O[H])Cl)Cl Hydrolysis 45360620 85 at pH 4 3.2 at pH 7 0.99 at pH 9 85 at pH 4 (21) 3.2 at pH 7 (21) 0.99 at pH 9 (21) Photolysis in soil 45360625 2.5 (30) 2.5 (30)

Aerobic soil metabolism 45360626 45360627 3.13 (150) 1.54 (200)

Aerobic soil metabolism 45360628 sandy loam 0.4 (300) 9.7(240)

Loam 17.1 (365) sandy loam 0 (365) 7.7 (365)

Loam 17.1 (365)

Terrestrial field dissipation 45360704 6.9 (30) <LOD (519)

45360705 9.7 (62) Not reliable detection

CFBPQ 2

- chloro

- 10

- fluoro

7a,11 a

dihydrochromeno[2,

3,4

- de]quinoline Formula: C 15 H 7 ClNO MW: 271.678 g/mol Smile string: C12=C3C=C(C=C1N=CC= C2OC4=C3C=C(C=C4)F)C l Photolysis in
water 45360623 42.5 (1) Not detected (28)

Photolysis in
water 45360624 91 (1 hr) 1.7 (7)

### 11 Code Name/ Synonym Chemical Name Chemical Structure Study Type Ref. (MRID) Maximum %AR (day) Final %AR (study length)

DCMQ 5,7

- dichloro

- 4

- methoxyquinoline Formula: C 10 H 7 Cl 2 NO MW: 228.08 Smile string: C1(=CC(=CC2=C1C(=CC= N2)OC)Cl)Cl Aerobic soil metabolism 45360628 Sandy loam 3.3 (300)

Loam 3.3 (365) Sandy loam 0 (365) Loam 3.3 (365)

CO 2 CAS No : 124

- 38

- 9

Formula: CO 2 MW: 44.01 g/mol Smile string: C(=O)=O Aerobic soil metabolism 45360628 Sandy loam 14.5 (365) 4.3 (365)

loam 22.5(365) 5.7 (365) Sandy loam 14.5 (365) 4.3 (365)

loam 22.5(365) 5.7 (365) 45360626 & 45360627 1.89 (150) 1.79 (200)

*Previously called 3

- OH

- quinoxyfen.

### 12 6. Receptors



### The most sensitive aquatic and terrestrial toxicity data for quinoxyfen and its degradates are summarized in Table 4 and Table 5

, respectively . Quinoxyfen is very highly toxic to aquatic invertebrates including D. magna (freshwater invertebrate), mysid shrimp ( A. bahia ; estuarine/marine crustacean), and Eastern oysters ( Crassostrea virginica ; estuarine/marine mollusk) on an acute exposure basis. The compound is highly toxic to the freshwater rainbow trout ( Oncorhynchus mykiss ) on an acute exposure basis. Definitive acute toxicity endpoints could not be established for the estuarine/marine sheepshead minnow ( Cyprinodon variegatus ) and the freshwa ter bluegill sunfish ( Lepomis macrochirus ) due to the low solubility ( 0.047 mg/L at 25 o 

### C at pH 7 ) of quinoxyfen.

On a chronic exposure basis, freshwater fathead minnows ( Pimephales promelas ) exhibited reduction s in growth (body length; NOAEC =13 μg ai/L). In the estuarine/marine sheepshead minnow, larval survival and growth (standard length and blotted wet weight) were the most sensitive measured endpoints (NOAEC=4.09 μg a.i./L ). The freshwater invertebrate D. magna exhibited reduced growth (length) and

r educed number of offspring fo llowing chronic exposure (NOAEC =27 μg a.i./L). Sediment toxicity data are available for non

- biting midge larvae, Chironomus riparius (freshwater invertebrate), which show reduced emergence (NOAEC =128 μg a.i./L) following a 27

- d ay exposure period; exposure was expressed in terms of water column concentrations rather than the preferred sediment pore water concentrations. In a 28

- day life

- cycle toxicity study with mysid shrimp, a definitive NOAEC could not be established since effe cts on reproduction (young per reproductive day) were observed at the lowest test level (0.91 μg a.i./L) , in which a 19% reduction in mean number of offspring per female per reproductive day was observed relative to the negative control. However, it should be noted that the mean number of offspring per female per reproductive day in the mysid study was higher in the 0.91 μg a.i./L treatment level than in the solvent control, indicating a potential solvent effect.

Quinoxyfen exhibits low acute toxicity to t errestrial animals. It is practically non

- toxic to birds (Northern bobwhite quail, Colinus virginianus, and mallard duck, Anas platyrhynchos ) on both an acute oral and subacute dietary exposure basis and is practically nontoxic to rats ( Rattus norvegicus ) on an acute oral exposure basis. Quinoxyfen is also practically non

- toxic to young adult honeybees on an acute contact exposure basis.

Chronic exposure to northern bobwhite quail resulted in decreased numbers of live/viable embryos and hat chling survival /eggs set (NOAEC =483 mg a.i./kg

- diet). Chronic exposure to mallards resulted in decreased survival of 14

- day old chicks at both the lowest (229 mg a.i./kg

- diet) and highest (933 mg a.i./kg

- diet) concentrations tested. Therefore, the original DER for this s tudy (MRID 45360412) concluded that the NOAEC

was non

- definitive ( i.e., NOAEC <229 mg a.i./kg

- diet) because significant reductions in 14

- day survivorship were detected at the lowest test level. However, based on current EFED policy, 14

- day survival is only considered as a ratio with another study measure

### 13 such as number of normal hatchlings or eggs set, and the 14

- day survival endpoint is no longer considered appropriate for risk assessment. Therefore, the most sensitive endpoint from this study is currently based on decreased numbers of live/viable embryos and the ratio of hatchling survival/eggs set at the highest test level (NOAEC= 465 mg a.i./kg

diet)

.

A two

- generation reproduction study with Sprague

- Dawley rats ( R

. norvegicus ) resulted in decreased body weights in offspri ng from chronic exposure (NOAEC =20 mg/kg

bw/day).

In pre

- emergent (seedling emergence) terrestrial plant toxicity testing, none of the 10 plant species tested exhibited a phytotoxic response following exposure to quinoxyfen at
concentra tions equivalent to an application rate of 0.5 lbs a.i./A. In vegetative vigor testing, only one of the 10 species tested exhibited a statistically significant phytotoxic response. The dicotyledonous (dicot) cucumber ( Cucumis sativus ) was found to exhibit reduction in fresh weight when exposed to quinoxyfen, with a effect concentration for 25% of the plants tested, i.e
., EC 25 

### , value of 0.37 lbs a

. i

. /A and a NOA EC of 0.06 lbs a.i./A . In both the seedling emergence and vegetative vigor studies, all species we re exposed to a single concentration of 553 g/ha (0.5 lbs a.i./acre), except for cucumber which was tested at 0.06

, 0.1 4, 0.26 , and 0.5 lbs ai/A.

In a 7

- day toxicity study of freshwater vascular plants with Lemna gibba (duckweed), n o significant differenc es were observed in frond number, growth rate, or dry weight endpoints relative to controls at any of the concentrations tested ( NOAEC and EC 50 

### values are 35 and >35 μg a.i. /L, respectively)

. Acute toxicity testing on nonvascular aquatic plants using gree n algae, Raphidocelis subcapitata (formerly Pseudokirchneriella subcapitata and Selenastrum capricornutum ) the freshwater diatom, Navicula pelliculosa , and the saltwater diatom, Skeletonema

costatu m , resulted in EC 50 

### values of 5 1, 30, and 130 μ g a.i./L, respectively, and were within the solubility range of quinoxyfen.

Table 4 . Summary of the Most Sensitive Toxicity Endpoints for Quinoxyfen.

Group Species (Common Name) Endpoint (Duration) Toxicity Value (Measured Effect) MRID (Study Classification) Aquatic Organisms

Freshwater Fish § Oncorhynchus mykiss (Rainbow Trout) LC 50 (96 hours) 270 μg a.i./L (Mortality) 45360413 (Supplemental) Pimephales promelas

(Fathead Minnow) NOAEC (28 days) 13 μg a.i./L (Growth: length) 45360424 (Acceptable)

Freshwater Invertebrates Daphnia magna (Water Flea) EC 50 (48 hours) 83 μg a.i./L * (Immobility) 45360417 (Acceptable)

NOAEC (21 days) 27.8 μg a.i./L (Growth; reproduction) 45360423 (Supplemental)

### 14 Group Species (Common Name) Endpoint (Duration) Toxicity Value (Measured Effect) MRID (Study Classification)

Estuarine/ Marine Fish Cyprinodon variegatus (Sheepshead minnow) LC 50 (96 hours) >168 μg a.i./L (Mortality) 45360420 (Supplemental)

NOAEC (39 days) 4.1 μg a.i./L (Growth; Survival) 48102302 (Acceptable)

Estuarine/

Marine Invertebrates Crassostrea virginica (Eastern Oyster) EC 50 (96 hours) 72 μg a.i./L (Shell Deposition) 45360421 (Acceptable) Americamysis bahia (Mysid shrimp) NOAEC (28 days) <0.91 μg a.i./L (Reproduction) 48102301 (Supplemental)

Vascular Plants Lemna gibba (duckweed) EC 50 (14 Days) >35 μg a.i./L (Frond number) 48387901 (Acceptable) NOAEC (14 Days) 35 μg a.i./L (Frond number)

Nonvascular Plants Navicula pelliculosa (freshwater diatom) EC 50 (120 Hours) 30 μg a.i./L (Cell Density) 45360615 (Acceptable) Raphidocelis subcapitata (green algae) NOAEC (120 hours) 6.36 μg a.i./L (Cell Density) 45360610 (Supplemental)

Terrestrial Organisms

Avian ‡ Colinus virginianus (Northern Bobwhite Quail) LD 50 (14 days) >2,292 mg a.i./kg

- bw (Survival) 45360407 (Acceptable) LC 50 (8 days) >5,620 mg/kg

- diet (Survival) 45360409 (Acceptable)

Anas platyrhynchos

(Mallard Duck) NOAEC (27 weeks) 465 mg a.i./kg

- diet † (numbers of live/viable embryos and hatchling survival/eggs set) 45360412 (Supplemental)

Mammals Rattus norvegicus (Laboratory Rat) LD 50 >5,000 mg a.i./kg

- bw 45360616 (Acceptable)

NOAEL 20 mg a.i./kg

- bw 400 mg a.i./kg

- diet 45360522 (Acceptable) Terrestrial Invertebrates Apis mellifera (European Honeybee) LD 50 (48 hours) >100 μg/bee 45360617 (Acceptable)

Plants (Vegetative

Vigor) Dicots EC 25 0.366 lbs a.i./A (plant weight)

45360607 (Acceptable) NOAEC 0.064 lbs a.i./A (plant weight)

Monocots EC 25 >0.5 lbs a.i./A (no effects at highest concentration tested)

NOAEC 0.5 lbs a.i./A (no effects at highest concentration tested) Plants (Seedling Emergence) Dicots EC 25 > 0.5 lbs a.i./A (no effects at highest concentration tested)

### 15 Group Species (Common Name) Endpoint (Duration) Toxicity Value (Measured Effect) MRID (Study Classification)

NOAEC 0.5 lbs a.i./A (no effects at highest concentration tested)

Monocots EC 25 >0.5 lbs a.i./A (no effects at highest concentration tested)

NOAEC 0.5 lbs a.i./A (no effects at highest concentration tested)

* Previous risk assessments used the LC 50 value from this study of 91 μg a.i./L, however, the EC 50 based on

immobility is more appropriate for risk assessment since immobile daphnids are considered to be dead. † In a memo date May 8, 2006 (DP Barcode D328427), the NOAEC for this study was changed from <292

to 465 mg a.i./kg

- diet. ‡ Birds are surrogates for terrestrial

- phase amphibians and reptiles. § Freshwater are surrogates for aquatic

- phase amphibians



### Since the last risk assessment of quinoxyfen, a mallard reproduction study with the transformation product 2

- oxo

- quinoxyfen was reviewed (48991801) . This study was requested because of the likely formation and persistence of 3

- OH quinoxyfen coupled with its stru ctural similarity to the parent 2



### . A t the highest test level in the submitted study ( 464 ppm dietary test concentration ) , there was a significant (p< 0.05) increa se in the number of eggs laid ( 37 %) and the number of eggs set ( 38%) c ompared to controls. Bas ed on the statistically significant increase on the number of eggs laid in the highest dietary treatment group, the NOAEC and LOAEC for mallards exposed to the degradate are 243 and 464 mg a

. i

. /kg diet, respectively . Since the lowest endpoint for the 2

- oxo

quinoxyfen avian reproduction study is lower than the lowest endpoint for the parent compound, the NOAEC from the 2

- oxo

- quinoxyfen study will be used to represent the toxicity of the parent compound for risk estimation during risk assessment.

Toxicologic al studies with D. magna indicate that both DCHQ and 2

- oxo

- quinoxyfen are at least five times less toxic than the parent compound. In addition, DCHQ is at least an order of magnitude less toxic to green algae as compared to quinoxyfen.

Table 5

. Summary of Degradate Toxicity Data

Group Species Endpoint (Duration) Toxicity Value (Measured Effect) MRID (Study Classification) DCHQ
Freshwater Invertebrates Daphnia magna EC 50 (48 Hours) >500 μg a.i./L 45360419 (Supplemental)
Nonvascular Plants Raphidocelis subcapitata EC 25 (96 Hours) >500 μg a.i./L 45360611 (Supplemental)

2 An avian reproduction study was submitted for 2

- oxo

- quinoxyfen rather than 3

- OH quinoxyfen because 2

- oxo quinoxyfen was initially misidentified as 3

- OH quinoxy fen in metabolism studies.

### 16 Group Species Endpoint (Duration) Toxicity Value (Measured Effect) MRID (Study Classification) (green algae) NOAEC (96 Hours) 500 μg a.i./L

2

- oxo - Quinoxyfen Freshwater Invertebrates Daphnia magna EC 50 (48 Hours) >500 μg a.i./L 45360418 (Supplemental)

Avian Anas platyrhynchos NOAEC 243 mg a.i./kg

- diet * 48991801 (Acceptable) * 2

- oxo

- quinoxyfen avian reproduction toxicity endpoint will be used to represent the parent (quinoxyfen) in risk estimation since birds were more sensitive to the transformation product as co mpared to the parent on a chronic exposure basis.

**a. Ecological Incidents** 



### The Ecological Incident Information S ystem (EIIS) is an OPP database that houses ecological incidents that have been reported to the Agency. When available, EIIS includes date and location of an incident, type and magnitude of effects observed in various species, use(s) of pesticides known o r suspected of contributing to the incident, and results of any chemical residue analysis or other analyses conducted during incident investigation. EIIS incidents are categorized according to the certainty that the incident resulted from pesticide exposu re. The Avian Monitoring System (AIMS) is a database administered by the American Bird Conservancy that contains publicly available data on reported avian incidents involving pesticides. Many of the incidents listed in this database are also in the EIIS.

A search of the EIIS for ecological incidents run on April 25, 2013 identified only a single incident that may have resulted from exposure to quinoxyfen. Incidents included in EIIS are defined by a certainty index associated with the likelihood that th e pesticide application described resulted in the observed incident. The certainty index defines incidents as unrelated, unlikely, possible, probable and highly probable. The only incident with quinoxyfen (I019772

- 008) involved damage to a cherry crop ( i.e

., plant damage) in California that was classified as “possible.” One note of uncertainty associated with this database is the nature of reporting of incidents. Many more incidents may have occurred due to quinoxyfen exposures but may not have been reporte d due to various factors, such as a lack of reporting, or a lack of observation of effects. Therefore, the lack of incident reports does not necessarily indicate the absence of incidents.

No plant or wildlife incidents have been reported through OPP’s agg regate incident report database and no avian incidents have been captured in the Avian Incident Monitoring System (AIMS; American Bird Conservancy 2009) 3 

### as of April 25, 2013.

3 Available at: http://www.abcbirds.org/abcprograms/policy/toxins/aims/aims/index.cfm

### 17 With respect to the one incident report on cherries, available toxicity data o n quinoxyfen indicated that terrestrial plants are relatively insensitive to the compound; however, one dicot, i.e ., cucumber, did provide a definitive EC 25 

### of 0.366 lbs a.i./A.

7. Exposure Pathways of Concern



### For a pesticide to pose an ecological risk, it must reach ecological receptors in biologically significant concentrations. An exposure pathway is the means by which a pesticide moves in the environment from a source to an ecological receptor. For an ecological pathway to be complete, it must include a source, a release mechanism, an environmental transport medium, a point of exposure for ecological receptors, and a feasible route of exposure.

The environmental fate properties of quinoxyfen indicate the following transport mechanisms for potential exp osure to aquatic and terrestrial organisms:

• Direct contact

• Spray drift

• Runoff

• Ingestion

The environmental fate properties and use patterns of quinoxyfen indicate that direct spray, spray drift, and runoff represent potential transport mechanisms of quinoxyfen to aquatic and terrestrial organisms. Drinking water and inhalation exposure pathways were screened using the SIP Screening Imbibition Program (SIP ) and Screening Tool for Inhalation Risk (STIR ) screening models and were found to be exposure pathways of low concern (no LOC exceedances are expected). SIP and STIR are described in detail at: http://www.epa.gov/oppefed1/models/terrestrial/inde x.htm

.

Both environmental fate properties ( i.e., K ow 

### and K oc 

### ) and BCF studies suggest that quinoxyfen has the propensity to bioaccumulate in the aquatic environment. Due to potential bioaccumulation concerns for quinoxyfen, KABAM (K OW 

### - based Aquatic Bioacc umulation Model) version 1.0 will be used to estimate potential bioaccumulation of quinoxyfen residues in the aquatic food web and the subsequent risks these residues pose to terrestrial organisms consuming aquatic species. The bioaccumulation portion of K ABAM is based upon work by Arnot and Gobas (2004) who parameterized a bioaccumulation model based on polychlorinated biphenyl ( PCB ) compound s and certain pesticides ( e.g ., lindane, DDT) in freshwater aquatic ecosystems. KABAM relies on a chemical's K ow 

### to estimate uptake and elimination constants through respiration and diet of organisms in different trophic levels. Pesticide tissue residues are calculated for organisms at different trophic levels in aquatic food webs. The model then uses pesticide tissue c oncentrations in aquatic animals to estimate dose

- and dietary

- based exposures and associated risks to mammals and birds (surrogate for terrestrial

- phase amphibians

### 18 and reptiles) consuming aquatic organisms. Additional information about KABAM can be found in the program user guide. 4

8. Analysis Plan



### In order to address the risk hypothesis, the potential for adverse effects on the environment is estimated. The use, environmental fate, and ecological effects of quinoxyfen are characterized and integrated to assess the risks. This is accomplished using a risk quotient (ratio of exposure concentration to effects concentration) approach. Although risk is often defined as the likelihood and magnitude of adverse ecological eff ects, the risk quotient

- based approach does not provide a quantitative estimate of likelihood and/or magnitude of an adverse effect. However, as outlined in the Overview Document ( USEPA, 2004), the likelihood of effects to individual organisms from partic ular uses of quinoxyfen is estimated using the probit dose

- response slope and either the level of concern (discussed below) or actual calculated risk quotient value.

This analysis plan will be revisited and may be revised depending upon the information

su bmitted by the public in response to the opening of the Registration Review docket for quinoxyfen.

**a. Stressors of Concern** 

i. Ecological Risk Assessment



### The stressors of concern are as follows:

• Terrestrial Environment: quinoxyfen (parent) and 2

- oxo

- quinoxyfen (transformation product)

• Aquatic Environment: quinoxyfen (parent)

The degradate 2

- oxo

- quinoxyfen (formerly identified as 3

- OH quinoxyfen , USEPA 2010 ) ) was considered a major degradate in the drinking water assessment ( USEPA 2013 b ) due to the structural simila rities with the parent compound. Dow AgroSciences (DAS) provided new information (MRIDs: 467613

- 01, 48133

- 01C and USEPA 2010 ) that demonstrated that 2

- oxo

- quinoxyfen is the correct degradate identified in the fate studies and no t 3

- OH

- quinoxyfen that was previously identified . Therefore, 2

- oxo

quinoxyfen is considered a major degradate in the drinking water assessment due to structural simila rities with the parent compound. Due to the more sensitive endpoint for avian reproductio n from 2

- oxo

- quinoxyfen versus the parent, 2

- oxo

- quinoxyfen is also being considered and stressor of concern for terrestrial ecological risk assessment. Conversely, for aquatic ecological risk assessment, only the parent is considered to be of

concern due to the demonstrated low toxicity of transformation products as compared with the parent

.

4 h ttp://www.epa.gov/oppefed1/models/water/

### 19 ii. Drinking Water



### The drinking water assessments conducted to support the registration review human health risk assessments of quinoxyfen will incorporate model estimates of residues of concern, which are parent compound and the 2

- oxo

- quinoxyfen degradate (USEPA, 2003 ; USEPA 2010 ), in surface and ground water source drinking water

. The Health Effects Division does not have sufficient data on the 2

- oxo

- quinoxyfen degradate to discount its potential toxicity. Therefore, quinoxyfen and 2

- oxo

- quinoxyfen will be assessed together using a total toxic residues approach.

**b. Measures of Exposure** 



### EFED will use st andard available models to evaluate potential exposures to aquatic and terrestrial organisms as described at http://www.epa.gov/pesticides/science/models_db.htm

.

i. Available Monitoring Data



### The Agency is not aware of surface or ground water monitoring conducted by federal and
state agencies. However, if new monitoring data of quinoxyfen becomes available, it will be considered in the assessment

.

**c. Measures of Effect** 



### Toxicity data presented i n Section 3 of this problem formulation will be used to calculate risk quotients. Any additional information submitted by the registrant or found in the open literature prior to conduct of the risk assessment meeting the standards established by the Agenc y will also be considered. The open literature studies are identified using EPA’s ECOTOXicology database ( ECOTOX) 5 

### , which employs a literature search engine for locating chemical toxicity data for aquatic life, terrestrial plants, and wildlife. The evalu ation of both sources of data can also provide insight into the direct and indirect effects of pesticides on biotic communities from loss of species that are sensitive to the chemicals and from changes in structure and functional characteristics of the aff ected communities.

**9. Endangered Species Assessments** 



### Consistent with the Agency’s responsibility under the Endangered Species Act (ESA), the Agency will evaluate risks to listed species from registered uses of pesticides in registration review

. The process for evaluating potential risks to listed species is further described at http://www.epa.gov/oppfead1/endanger/litstatus/riskasses.htm

.

5 http://cfpub.epa.gov/ecotox/

### 20 **10. Endocrine Disruptor Screening Pro**  **gram**



### Quinoxyfen was not included in the first group of 67 chemicals issued an order to conduct Tier 1 EDSP testing. For additional information the EDSP program, visit http://www.epa.gov/endo/

.

**11. Preliminary**  **Identification of Data Gaps**

a. Environmental Fate



### Environmental Chemistry Methods (ECM) for Soil and Water and Associated Independent Laboratory Validation (ILV), OCSPP Guideline 850.6100 is needed to support field dissipation studies

.

ECM and ILV are not available for the methods used in the field dissipation studies

, though this is a requirement for acceptance of such studies. Environmental chemistry methods in water as well as soil (along wi th associated ILV) are required in field dis sipation and ground water monitoring studies under the OCSPP 835 Environmental Fate Test Guidelines, or used in field studies of terrestrial and aquatic organisms and plants under the OCSPP 850

.

Table 6 i dentifies environmental fate studies

, by MRID

, that provide data for each guideline requirement, as well as study classifications and whether or not further data are needed in order to support risk assessment. No environmental fate data for degradates have been submitted; however at this time no studi es on quinoxyfen degradates are needed for risk assessment

.

Table 6 . Submitted Environmental Fate Data for Quinoxyfen

.

OCSPP Guideline Data Requirement Submitted MRIDs Study Classification Are data needed to conduct risk

assessment? Justification and Assu mptions EPA will Make in Absence of Data

835.2120 Hydrolysis 45360620 Acceptable No

835.2370 Aqueous Photolysis 45360623,
45360624 Supplemental Supplemental No

835.2410 Soil Photolysis 45360625 Acceptable No

835.4100 Aerobic Soil Metabolism 45360626 Supplemental No

### 21 OCSPP Guideline Data Requirement Submitted MRIDs Study Classification Are data needed to conduct risk

assessment? Justification and Assu mptions EPA will Make in Absence of Data

45360627 Acceptable

835.4200 Anaerobic Soil Metabolism 45360711 Supplemental No

835.4300 Aerobic Aquatic Metabolism 45360630 Acceptable No

835.4400 Anaerobic Aquatic Metabolism 45360629 Acceptable No

835.1230 Adsorption/Deso rption batch equilibrium 45360701 Supplemental No

45360703 Acceptable

835.1240 Aged Column Leaching 45360702 Supplemental No

835.1410 Lab Volatility 45461303 Supplemental No

835.6200 Terrestrial; Field Dissipation 45360704 Acceptable

No 45360705 Acceptable

45360708 Supplemental

45360709 Supplemental

45360710 Supplemental

835.6100 Aquatic Field Dissipation 45360706 Not reviewed

-- 45360707 Not reviewed

850.6100 Environmental Chemistry Methods (ECM) and Independent Laboratory Validation (ILV) in soil and water N/A Not submitted Yes This is a standard data requirement for field dissipation and ground water monitoring studies

. ECM and associated ILV are not available for the method used in the field dissipation studies

,

though this is a requirement for acceptance of such studies.

### 22 OCSPP Guideline Data Requirement Submitted MRIDs Study Classification Are data needed to conduct risk

assessment? Justification and Assu mptions EPA will Make in Absence of Data

850.1730 Bioconcentration in Fish 45360425 48488501
48488501
48488501 Acceptable Acceptable Supplemental Supplemental No

b. Effects



### Table 7 identifies ecological effects studies with quinoxyfen

, by MRID

, for each guideline requirement, as well as study classifications and whether or not additional data are needed in order to support risk assessment. Rationale for the additional data requested is presen ted below the tables. Table 8 identifies ecological effects studies with transformation products of quinoxyfen.

Table 7 . Submitted Ecological Effects Data for Quinoxyfen

Guideline Description

— Test Substance MRID Study Classification Are data Needed for Risk Assessment ? Comments (Justification and Assumptions EPA will Make in Absence of Data)

Avian and Mammalian Testing

850.2100 Avian acute oral toxicity, waterfowl

— TGAI None N/A No

Avian acute oral toxicity, upland game bird

species

— TGAI 45360407 Acceptable No Five concentrations tested ; no treatment

- related mortalities. Study tests up to doses greater than 10 times the dose

- based EEC across uses and dietary items

.
Avian acute oral toxicity, passerine species

— TGAI None N/A No Study is not recommended because of low acute oral toxicity

to upland game birds and low dietary toxicity to upland game birds and waterfowl

850.2200 Avian dietary toxicity, waterfowl species

— TGAI 45360410 Acceptable No Five concentrations tested ; no treatment

- related mortalities. Study tests up to concentratio ns greater than 10 times the dietary

EEC across uses and dietary items

.

### 23 Guideline Description

— Test Substance MRID Study Classification Are data Needed for Risk Assessment ? Comments (Justification and Assumptions EPA will Make in Absence of Data)

Avian dietary toxicity, upland

game bird

— TGAI 45360409 Acceptable No Five concentrations tested ; no treatment

- related mortalities. Study tests up to concentrations

greater than 10 times dietary EEC across uses and dietary items.

850.2300 Avian reproduction,

waterfowl species

— TGAI 45360412 Supplemental No

Avian reproduction, upland game bird

species

— TGAI 45360411 Acceptable No

850.2400 Wild mammal toxicity

— TGAI None N/A No Not triggered based on ecotoxicity data, predicted EECs,

fate properties, and use pattern criteria.

850.2500 Simulated or actual field testing

— TEP None N/A No Not triggered based on ecotoxicity data, predicted EECs,

fate properties, and use pattern criteria. Aquatic Animal Testing

850.1010 Freshwater invertebrate, acute toxicity

— TGAI 45360417 Acceptable No

850.1025 Estuarine/Marine Mollusk acute toxicity

— TGAI 45360421 Acceptable No

850.1035 Estuarine/Marine
crustacean acute toxicity

— TGAI 45360422 Acceptable No

850.1075 Freshwater fish, acute toxicity,

warm water species

— TGAI 45360414 Supplemental No

Freshwater fish,

acute toxicity,

cold water species

— TGAI 45360413 Supplemental No

### 24 Guideline Description

— Test Substance MRID Study Classification Are data Needed for Risk Assessment ? Comments (Justification and Assumptions EPA will Make in Absence of Data)

Freshwater fish,

acute toxicity,

additional species

— TGAI 45360416 Supplemental No Study performed with Cyprinus carpio , which is not a recommended species for acute toxicity testing; however, results may be useful for risk
assessment.
Estuarine/Marine fish acute toxicity

— TGAI 45360420 Supplemental No

850.1300 Freshwater invertebrate, reproduction
test

— TGAI 45360423 Supplemental No Replicate data were not provided for statistical verification of dry weight data.

850.1350 Estuarine/marine invertebrate, reproduction
test

— TGAI 48102301 Supplemental Yes Study did not establish a NOAEC. Effects on number of offspring per reproductive day were observed at all concentrations tested.

850.1400 Freshwater fish, early life stage

test

— TGAI 45360424 Acceptable No

Saltwater fish, early life stage

test

— TGAI 48102302 Acceptable No

850.1500 Freshwater fish life cycle test None N/A No Aquatic EECs are < 0.1 of the FW fish ea rly life

- stage (ELS) NOAEC (13 μ g a.i./L ).
Estuarine/marine

fish life cycle
test None N/A No Aquatic EECs are < 0.1 of the EM fish early life

- stage (ELS) NOAEC (4.1 μg a.i./L).

850.1950 Simulated or actual field testing for

aquatic organisms None N/A No Higher tier testing to address risk uncertainties have not been identified at this time.

Non

Guideline Freshwater fish 21

- day sub

chronic toxicity
test 45360415 Supplemental No Subchronic testing with freshwater fish is not required, but study results may be useful for risk assessment.

### 25 Guideline Description

— Test Substance MRID Study Classification Are data Needed for Risk Assessment ? Comments (Justification and Assumptions EPA will Make in Absence of Data)

Sediment Testing

850.1735 Whole sediment 10

- d freshwater invertebrate

— TGAI None N/A Yes Data requirement triggered since K OC and log K ow values in submitted fate studies were above 1,000 and 3.0, respectively (see Appendix E and data justification below table for further details)

850.1740 Whole sediment 10

- d estuarine/marine

invertebrate

— TGAI None N/A Yes Data requirement triggered since K OC and log K ow values in submitted fate studies were above 1,000 and 3.0, respectively (see Appendix E and data justification below table for further details)

Agency

wide guideline Whole sediment chronic freshwater and/or marine invertebrate

— TGAI None N/A Yes Data are recommended pending the outcome of the 10

- day sediment toxicity studies (850.1735; 850.1740) (see

Appendix E and data justification below table for further details) Insect Pollinator Testing

850.3020 Honeybee acute
contact toxicity

— TGAI 45360616 Acceptable No

45360617 Acceptable No

Non

guideline Honeybee acute oral toxicity study

— TGAI 453606178 Supplemental No

850.3030 Honeybee toxicity of residues on foliage

— TEP None N/A No Data requirement not triggered

850.3040 Field testing for pollinators None N/A No Field testing to address risk uncertainties have not been identified at this time

### 26 Guideline Description

— Test Substance MRID Study Classification Are data Needed for Risk Assessment ? Comments (Justification and Assumptions EPA will Make in Absence of Data)

Non

guideline Larval Toxicity Test

— TGAI None N/A Yes D ata are only available on the toxicity of quinoxyfen to young

adult bees; no information is available on toxicity of quinoxyfen to honeybee larvae

. A honeybee larval toxicity test is part of EFEDs current screening process for terrestrial invertebrates.

A protocol should be submitted

before conducting this te st.

See Appendix E for further justification for recommending this study. Terrestrial Plant Testing

850.4100 Seedling emergence (10 species)

— TEP 45360607 Acceptable No Although not noted in the DER, quinoxyfen was tested as a suspension concentrate which the

study authors described as TEP 850.4150 Vegetative vigor (10 species)

— TEP No

Aquatic Plant Testing

850.4400 Aquatic plant growth, vascular plant

— TGAI 48387901 Acceptable No Test was conducted up to maximum experimental solubility limit

45360612 Supplemental No NOAEC and EC 05 could not be determined due to significant toxicity at all treatment levels.

850.4500* Aquatic Plant, freshwater green

alga species

— TGAI 45360610 Supplemental No Extensive cell count variability in control groups

Aquatic Plant,

freshwater

diatom

— TGAI 45360615 Acceptable No

Aquatic Plant, marine diatom

— TGAI 45360613 Supplemental No

### 27 Guideline Description

— Test Substance MRID Study Classification Are data Needed for Risk Assessment ? Comments (Justification and Assumptions EPA will Make in Absence of Data)

850.4550 † Aquatic Plant, cyanobacterium

— TGAI 45360614 Acceptable No

TGAI = Technical Grade Active Ingredient TEP = technical end product * Algal toxicity tests are now under guideline OCSPP 850.4500 (formerly 850.5400) † Cyanobacterium tests are now under guideline 850.4550 (formerly 850.5400)



### Table 8 . Submitted Ecological Effects Data for Quinoxyfen Transformation P roducts.

Guideline Description

— Test Substance MRID Study Classificatio

n Are data Needed for Risk Assessment ? Comments (Justification and Assumptions EPA will Make in Absence of Data)

850.2300 Avian reproduction,

waterfowl species

— 2

- Oxo

Quinoxyfen 48991801 Acceptable No Study review date: June 17, 2013

850.1010 Freshwater invertebrate, acute toxicity

— 3

- OH Quinoxyfen 45360418 Supplementa l No Limit test; only nominal concentration was reported

invertebrate, acute toxicity

— DCHQ 45360419 Supplementa l No Limit test; only nominal concentration was reported

850.4500 * Aquatic Plant, freshwater green alga species

—

DCHQ 45360611 Supplementa l No Only one limit concentration tested and test concentration was not measured during study.

* Algal toxicity tests are now under guideline OCSPP 850.4500 (formerly 850.5400)

12. References

Goring, C.A. I.; Laskowki; D.A., Hamaker, J.H.; and Me ikle, R.W. 1975. Principles of pesticide degradation in soil. pp. 135

- 172 in (Haque, R. and Freed, V.H. eds.) Environmental dynamics of pesticides. Plenum Press, NY.

### 28 USDA Crop Profiles. Available online at: http://www.ipmcenters.org/cropprofiles/CP_form.cfm

Food and Agriculture Organization of the United Nations. FAO Pesticide Disposal Series 8. Assessing Soil Contamination: A Reference Manual. Appendix 2. Parameters of pesticides that influence processes in the soil. Editorial Group, FAO Information Division: Rome, 2000. http://www.fao.org/docrep/003/X2570E/X2570E00.htm

. Jones, R.D. et al., 2000. Guidance for use of the Index Reservoir and Percent Crop Area Factor in Drinking Water Assessments (March 21, 2000). Office of Pesticide Programs, Environmental Fate and Effects Division, U.S. Environmental Protection Agency. Arlington, VA.

SCHER (2011) SCHER (Scientific Committee on Health and Environmental Risks), Opinion on draft environmental quality standards under the Water Framewor k Directive

– quinoxyfen, 15 June 2011.

Wheeler, I. E., Hollomon, D. W., Gustafson, G., Mitchell, J. C. , Longhurst, C., Zhang, Z. and Gurr, S. J. (2003). Quinoxyfen perturbs signal transdu ction in barley powdery mildew (Blumeria graminis f.sp. hordei). Mo lecular Pla nt Pathology, 4: 177

– 186. doi: 10.1046/j.1364

- 3703.2003.00165.x

USEPA. 1999. Guidance for Use of the Index Reservoir in Drinking Water Exposure Assessments. Arlington, VA.

USEPA. 2000. Drinking Water Screening Level Assessment. Part A: Applying a Percent Crop Area Adjustment to Tier II Surface Water Model Estimates for Pesticide Drinking Water Exposure Assessments. FQPA Science Policy Document .Public Comment Draft September 1, 2000. Federal Register: October 11, 2000 (volume 65, number 197). Electronic copy available at http://www.epa.gov/pesticides/trac/science/ .

USEPA. 2002a. Guidance for Selecting Input Parameters in Modeling the Environmental Fate and Transport of Pesticides, Version II (February 28, 2002). Office of Pesticide P rograms, Environmental Fate and Effects Division, U.S. Environmental Protection Agency. Arlington, VA.

USEPA. 2002b. Pesticide Root Zone Model (PRZM) Field and Or chard Crop Scenarios: Standard Procedures for Conducting Quality Control and Quality Assuranc e. O ffice of Pesticide Programs, Environmental Fate and Effects Division, U.S. Environmental Protection Agency. Arlington, VA.

USEPA 2003a

. Quinoxyfen

- Health Effects Division (HED) Metabolism Assessment Review Committee (MARC) Decision Document. Meeting date March 5, 2003. United States Environmental Protection Agency (USEPA) . Health and Effects Division.

USEPA 2003b. Environmental Fate and Ecological Risk Assessment for the Registration of Quinoxyfen. United States Environmental Protection Agency (USEPA). Environmental Fate and Effects Division. Memorandum issue: August 5, 2003.

USEPA. 2004. Overview of the Ecological Risk Assessment Pro cess in the Office of Pesticide Programs . United States Environmental Protection Agency (USEPA). Environmental

### 29 Fate and Effects Division. Office of Pesticide Programs. Available at ht tp://www.epa.gov/espp/consultation/ecorisk

- overview.pdf

. USEPA 2008. Quinoxyfen: Tier I Drinking Water Exposure Assessment in Support of the Proposed New Uses of Quinoxyfen on stone frui ts group 12 (excluding cherry), artichokes, winter squash, pumpkin an d edible gour ds. United States Environmental Protection Agency (USEPA). Environmental Fate an d Effects Division. Memorandum issued: October 20, 2008.

USEPA 2010. Response to Data Submission from Dow AgroSciences Dated June 24, 2010: Structure of Soil Metabolite. A MEMORANDUM from the Environmental Fate and Effects Division to Registration Division. DP Barcode 380219 

### . Dated August 12, 2010.

USEPA 2013 a

. Reduced Risk Analysis: Quinoxyfen Use on F ruiting Vegetables Group 8

- 10B (Tomatoes). United States Environmental Protection Agency (USEPA). Envir onmental Fate and Effects Division. Memorandum issued: April 4, 2013.

USEPA 2013 b

. Tier I Drinking Water Ass essment for the IR

- 4 Ne w Use Petitions for the Use of Quinoxyfen on Fruiting Vegetables Group 8

- 10B, Sm all Fruit Vine Climbing Except Fuzzy Kiwifruit Subgroup 13

- 07F and Low Growing Berry Subgroup 13

- 07G. United States Environmental Protection Agency (USEP A). Environmental Fate and Effects Division. Memorandum issued: April 23, 2013.

USEPA, 2013c. Environmental Fate and Ecological Risk Assessment for Proposed Use of Quinoxyfen on Fruiting Vegetables Group 8

- 10B, Small Fruit Vine Cli mbing (Except Fuzzy Kiwifruit) Subgroup 13

- 07F and Low Growing Berry Subgroup 13

- 07G. United States Environmental Protection Agency (USEPA). Environme ntal Fate and Effects Division. Memorandum issued: May 22, 2013.

USEPA. 2013 d

. BEAD Chemical Profile for Registration R eview: Quinoxyfen (121027)

. Memorandum From Don Atwood

, Jihad Alsadek and Stephen Smearman to Bonnie Alder. Biological and Economic Analysis Division to Pesticide Reevaluation Division.

### 30 Appendix A. Submitted Environmental Fate and Effects Studies

SUBMIT TED FATE STUDIES (as of 06/04/13)

161

- 1 Hydrolysis

MRID Citation Reference

45360619 Cowlyn, T. (1993) XDE

- 795 (Pure): Determination of Hydrolysis as a Function of pH; Amended Final Report: Lab Project Number: GHE

- P

- 3072. Unpublished study prepared by Pharmaco

- LSR Ltd. 32 p.

45360620 Reeves, G.; Ghosh, D. (1994) The Hydrolysis of (carbon 14)

- XDE

- 795: Lab Project Number: GHE

- P

- 3137. Unpublished study prepared by DowElanco Europe. 90 p.

45461302 Baloch, R. (1997) Effects of Buffer and Co

- Solvent on the Hydrolysis of DE

795: Lab Project Number: GHE

- P

- 6328: E97

- 041. Unpublished study prepared by DowElanco Europe. 45 p.

161

- 2 Photodegradation

- water

45360621 Rudel, H. (1995) Determination of t he Quantum Yield of XDE

- 795 in Water: Lab Project Number: GHE

- P

- 4429. Unpublished study prepared by Umweltchemie und Okotoxikologie

-- IUCT. 62 p.

45360622 Portwood, D. (1996) Identification of DE

- 795 in Photolysis Products: Lab Project Number: GHE

- P

- 4721. Unpublished study prepared by DowElanco Europe. 68 p.

45360623 MacDonald, A. (1997) The Photolysis of (carbon 14)

- DE

- 795 Under Natural Conditions: Lab Project Number: GHE

- P

- 5932: 26Q. Unpublished study prepared by DowElanco Europe. 101 p.

45360624 Yoder, R.; Schwedler, D. (2001) Aqueous Photolysis of Quinoxyfen in pH Buffer Under Xenon Light: Lab Project Number: 000116. Unpublished study prepared by Dow AgroSciences LLC. 104 p.

161

- 3 Photodegradation

- soil

45360625 Reeves, G. (1995) The Soil Photolysis of (carbon 14)

- XDE

- 795: Lab Project Number: GHE

- P

- 4111: 16Q. Unpublished study prepared by DowElanco Europe. 74 p.

162

- 1 Aerobic soil metabolism

45360626 Reeves, G. (1993) The Aerobic Soil Degradation/Metabolism of (carbon 14)

- XDE

- 795 an d the Effect of Environmental Conditions on its Degradation Rate: Lab Project Number: GHE

- P

- 2990. Unpublished study prepared by DowElanco Europe. 78 p.

45360627 Ghosh, D.; Portwood, D. (1994) Identification of Soil Metabolism Products of XDE

- 795 by Parti cle

- Beam Liquid Chromatography Mass Spectrometry and

### 31 Thermospray Liquid Chromatography Mass Spectrometry: Lab Project Number: GHE

- P

- 3079. Unpublished study prepared by DowElanco Europe. 52
p.

45360628 Krieger, M.; Smith, K.; Balcer, J. (2001) Aerobic Soi l Metabolism of Quinoxyfen: Lab Project Number: 990062. Unpublished study prepared by Dow AgroSciences LLC. 145 p.

162

- 2 Anaerobic soil metabolism

45360711 Phillips, M.; Hall, B. (1995) The Degradation of Radiolabelled XDE

- 795 in Soul Under Anaerobic Conditions: Lab Project Number: GHE

- P

- 4374. Unpublished study prepared by Inveresk Research International. 57 p. {OPPTS 835.3400}

162

- 3 Anaerobic aquatic metab.

45360629 Krieger, M.; Smith, K.; Balcer, J. (2001) Anaerobic Aquatic Metabolism of Quinoxyfen: Lab Project Number: 990063. Unpublished study prepared by Dow AgroSciences LLC. 88 p.

162

- 4 Aerobic aquatic metab.

45360630 Batzer, F.; Simon, K. (2001) The Aerobic Aquatic Metabolism of Quinoxyfen: Lab Project Number: 000135. Unpublished study prepared by Dow AgroSciences LLC. 98 p.

163

- 1 Leach/adsorp/desorption

45360701 Reeves, G. (1994) The Adsorption/Desorption of (carbon

- 14)

- XDE

- 795 in Soil: Lab Project Number: GHE

- P

- 3592. Unpublished study prepared by DowElanco Europe. 53 p.

45360702 Reeves, G. (1994) The Leaching Characteristics of Aged (carbon

- 14)

- XDE

- 795 Soil Residues: Lab Project Number: GHE

- P

- 3552. Unpublished study prepared by DowElanco Europe. 52 p.

45360703 Sarff, P.; Damon, A. (2001) Soil/Sediment Adsorption Desorption of Quinoxyfen, 3

- Hydroxyquinoxyfen, and 5,7

- Dichloro

- 4

- hydroxyquinoline for US Registration: Lab Project Number: 11344088

- 5029

- 1: 000372: 46296. Unpublished study prepared by ABC Laboratories, Inc. 224 p.

163

- 2 Volatility

- lab

45461303 Ruedel, H. (1997) Testing of the Volatilisation Potent ial of XDE

- 795: Volatilisation from Plant Surfaces, Volatilisation from Soil: Lab Project Number: DOW

- 025/7

- 22 (15Q). Unpublished study prepared by Fraunhofer

Institut fuer Umweltchemie und Oekotoxikologie. 62 p.

164

- 1 Terrestrial field dissipation

### 32 45360704 Roberts, D.; Foster, D. (2001) Field Dissipation of Quinoxyfen Under California Irrigated Conditions: Lab Project Number: 990025: A020.004. Unpublished study prepared by Dow AgroSciences LLC and Excel Research Services, Inc. 162 p.

45360705 Roberts, D.; Foster, D. (2001) Field Dissipation of Quinoxyfen in Ontario, Canada: Lab Project Number: 990046. Unpublished study prepared by Dow AgroSciences LLC and Vaughn Agricultural Research Services, Ltd. 170 p.

164

- 2 Aquatic field dissipation

MRID Citation Reference

45360706 Olberding, E. (2001) Method Validation Report for the Determination of XDE

- 795 (Quinoxyfen) and the 3

- Hydroxy Metabolite Residues in Soil Using Dow AgroSciences Method ERC 94.27: Lab Project Number: GH

- C 5193: ERC 94.27. Unpublished study prepared by Dow A groSciences Europe. 39 p. {OPPTS 850.7100}

45360707 Olberding, E.; Foster, D. (2001) Method Validation Report for the Determination of Quinoxyfen and Metabolites in Soil by Gas Chromatography with Tandem Mass Spectrometry Detection Using Dow AgroSciences Method GRM 00.16: Lab Project Number: 000420: GRM 00. 16. Unpublished study prepared by Dow AgroSciences LLC. 50 p. {OPPTS 850.7100}

165

- 1 Confined rotational crop

45360713 Haq, R.; Brown, G. (1995) Uptake of XDE

- 795 into Three Succeeding Crops: Lab Project Number: GHE

- P

- 4322: 9 Q. Unpublished study p repared by DowElanco Europe. 56 p. {OPPTS 860.1850}

Non

- Guideline Study Selections

45360708 Gambie , A. et al. (1999) Residues of Quinoxyfen and its 3

- Hydroxy Metabolite in Soil Following Five Annual Applications of EF

- 1186, Northern France

- 1993: Lab Project Number: GHE

- P

- 7336R: R93

- 041. Unpublished study prepared by Dow AgroSciences. 56 p.

45360709 Gambie, A. et al. (1999) Residues of Quinoxyfen and its 3

- Hydroxy Metabolite in Soil Following Five Annual Applications of EF

- 1186, Germany: Lab Project Number: GHE

- P

- 7337R: RF93

- 42: RL93

- 42. Unpublished study prepared by Dow AgroSciences. 78 p.

45360 710 Khoshab, A. (2000) Residues of Quinoxyfen and its 3

- Hydroxy Metabolite in Soil Following Five Annual Applications of EF

- 1186, UK

- Final Report: Lab Project Number: GHR

- P

- 8686: R93

- 43. Unpublished study prepared by Dow AgroSciences Europe. 65 p.

453607 12 Krieger, M.; Roberts, D. (2001) Environmental Fate Summary of Quinoxyfen: Lab Project Number: GH

- C 5200. Unpublished study prepared by Dow

### 33 AgroSciences LLC. 81 p.

45360719 Rawle, N.; Gambie, A. (1995) Independent Validation of DowElanco Method ERC 94.27 for the Determination of Residues of XDE

- 795 and its 3

- Hydroxy Metabolite in Soil: Lab Project Number: REV95

- 03: GHE

- P

- 4184: ERC 94.27. Unpublished study prepared by CEM Anal ytical Services Ltd. 49 p.

45360725 Gambie, A. (2001) The Stability of XDE

- 795 and the 3

- Hydroxy Metabolite in Soil Under Frozen Storage Conditions (30 Months): Lab Project Number: GHE

- P

- 7935: ST94

- 11. Unpublished study prepared by Dow AgroSciences Eur ope. 29 p.

48133301 Terando, N. (1995) Synthesis of 5,7

- Dichloro

- 4

- (4

- Fluorophenoxy)

- 3

- Hydroxyquinoline (X510421, DE

- 795 Metabolite). Project Number: GH/C/3841. Unpublished study prepared by DowElanco. 52 p.

48133302 Terando, N. (1999) Synthesis of 5 ,7

- Dichloro

- 4

- (4

- Fluorophenoxy)

- 3

- Hydroxyquinoline (Quinoxyfen, DE

- 795 Metabolite). Project Number: GH/C/4915. Unpublished study prepared by Dow AgroSciences, LLC. 25 p.

71

- 1 Avian Single Dose Oral Toxicity

MRID Citation Reference

45360407 Campbell, S.; Lynn, S. (1992) XDE

- 795 Fungicide An Acute Oral Toxicity Study with the Northern Bobwhite: Lab Project Number: ES

- DR

- 0325

- 7474

- 5: ES

- 2543. Unpublished study prepared by Wildlife International Ltd. 21 p.

45360408 Lehr, K.; Rathkamp, W. (1992) 5,7

- Dichloro

- 4

- (4

- Fluorophenoxy) Quinoline (XR

795): Stability in Prepared Game Bird Starter Ration: Lab Project Number: ES

- DR

0325

- 7474

- 3. Unpublished study prepared by Wildlife International Ltd. 16 p.

71

- 2 Avian Di etary Toxicity
MRID Citation Reference

45360409 Campbell, S.; Lynn, S. (1992) XDE

- 795 Fungicide A Dietary LC50 Study with the Northern Bobwhite: Lab Project Number: 103

- 377: ES

- 2541: ES

- DR

- 0325

- 7474

- 7. Unpublished study prepared by Wildlife International Ltd. 20 p.

45360410 Campbell, S. (1992) XDE

- 795 Fungicide A Dietary LC50 Study with the Mallard: Lab Project Number: 103

- 378: ES

- 2544: ES

- DR

- 0325

- 7474

- 6. Unpublished study prepared by Wildlife International Ltd. 21 p.

71

- 4 Avian Reproduction

MRID Citation Reference

45360411 Helsten, B. (1999) Avian Reproductive Toxicity Study with Quinoxyfen in Bobwhite Quail: Lab Project Number: 153

- 017

- 07: 981046. Unpublished study prepared by Bio

Life Associates, Ltd. 443 p.

### 34 45360412 Pedersen, C. (2000) Avian Reproductive Toxicity Study with Quinoxyfen in Mallard Ducks: Lab Project Number: 153

- 019

- 08: 990104. Unpublished study prepared by Bio

Life Associates, Ltd. 389 p.

47682501 Temple, D. (2007) 2

- Oxo

- Quinoxyfen Metabolite: A Repro duction Study with the Mallard. Project Number: 379/031607/MR/100P/4. Unpublished study prepared by Wildlife International, Ltd. 16 p.

72

- 1 Acute Toxicity to Freshwater Fish

MRID Citation Reference

45360413 Woodburn, K.; Hugo, J.; Kirk, H. (1993) The Acute 96

- Hour Toxicity of XDE

- 795 to the Rainbow Trout, Oncorhynchus mykiss Walbaum: Lab Project Number: DECO

- ES

2635. Unpublished study prepared by The Dow Chemical Company. 29 p.

45360414 Rick, D.; Hugo, J.; Kirk, H. et al. (1993) XDE

- 795 Fungicide: Acute 96

- Hour Flow

through Toxicity in Bluegill, Lepomis macrochirus Rafinesque: Lab Project Number: DECO

- ES

- 2659. Unpublished study prepared by The Dow Chemical Company. 31 p.

45360415 Rick, D.; Weinberg, J.; Martin, M. et al. (1994) Evaluation of the Prolonged (21

- Day)Toxicity of XDE

- 795 Fungicide to the Rainbow Trout, Oncorhynchus mykiss Walbaum: Lab Project Number: DECO

- ES

- 2668. Unpublished study prepared by The Dow Chemical Company. 35 p.

45360416 Sword, M.; Bowman, J.; Muckerman, M. (1996) Acute Static Renewal Toxicity of XDE

- 795 Fungicide to Common Carp (Cyprinus carpio): Lab Project Number: 42597: GHE

- T

- 621. Unpublished study prepared by ABC Laboratories, Inc. 289 p.

72

- 2 Acut e Toxicity to Freshwater Invertebrates

MRID Citation Reference

45360417 Milazzo, D.; Brown, R.; Servinski, M et al. (1993) XDE

- 795 Fungicide: Acute Toxicity to the Daphnid, Daphnia magna Straus: Lab Project Number: DECO

- ES

- 2600. Unpublished study prepared by The Dow Chemical Company. 26 p.

45360418 Marino, T.; Staley, J. (2000) 5,7

- Dichloro

- 4

- (4

- Fluorophenoxy)

- 3

- Hydroxyquinoline (3

- Hydroxy

- DE

- 795): An Acute Toxicity Study with the Daphnid, Daphnia magna Straus: Lab Project Number: 001134. Unpublished study prepared by The Dow Chemical Company. 23 p.

45360419 Marino, T.; Staley, J. (2000) 5,7

- Dichloro

- 4

- (4

- Fluorophenoxy)

- 3

- Hydroxyquinoline (3

- Hydroxy

- DE

- 795): An Acute Toxicity Study with the Daphnid, Daphnia magna Straus: Lab Project Number: 001132. Unpublished study prepared by The Dow Chemical Comp any. 23 p.

72

- 3 Acute Toxicity to Estuarine/Marine Organisms
MRID Citation Reference

45360420 Boeri, R.; Wyskiel, D.; Ward, T. (2000) Quinoxyfen (XDE

- 795) Technical: Acute Toxicity Study to the Sheepshead Minnow, Cyprinodon variegatus: Lab Project Number: 000108: 2040

- DO. Unpublished study prepared by T.R. Wilbury Laboratories, Inc. 25 p.

### 35 45360421 Boeri, R.; Wyskiel, D.; Ward, T. (2000) Quinoxyfen (XDE

- 795) Technical: Oyster Shell Deposition Test: Lab Project Number: 2034

- DO: 000106. Unpublished study prepared by T.R. Wilbury Laboratories, Inc. 24 p.

45360422 Boeri, R.; Wyskiel, D.; Ward, T. (2000) Quinoxyfen (XDE

- 795) Technical: Acute Toxicity to the Mysid, Americamysis bahia: Lab Project Number: 2033

- DO: 000107. Unpublished study prepared by T.R. Wilbury Laboratories, Inc. 26 p.

72

- 4 Fish Early Life Stage/Aquatic Invertebrate Li fe Cycle Study

MRID Citation Reference

45360424 Rhodes, J.; Downing, J.; Muckerman, M. (1996) Early Life

- Stage Toxicity of XDE

- 795 Technical to the Fathead Minnow (Pimephales promelas) Under Flow

- through Conditions: Lab Project Number: 42536: GHE

- T

- 590. Unpublished study prepared by ABC Laboratories. 63 4 p.

48102301 Aufderheide, J. (2006) Quinoxyfen: Life Cycle Toxicity Test of the Saltwater Mysid, Americamysis bahia, Conducted Under Flow

- Through Test Conditions. Project Number: 49242, 040427. Unpublished study prepared by ABC Laboratories, Inc. 68 p.

72

- 5 Life cycle fish

MRID Citation Reference

45360423 Kirk, H.; Servinski, M.; Milazzo, D. et al. (1995) XDE

- 795 Fungicide: Evaluation of the Chronic Toxicity (21

- Day Flow

- Through) to Daphnia magna Straus: Lab Project Number: DECO

- ES

- 2603. Unpublished study prepared by The Dow Chemical Company. 77 p.

123

- 1 Seed germination/seedling emergence and vegetative vigor

MRID Citation Reference

A.

45360607 McCormick, R. (2001) Effect of Quinoxyfen on the Emergence and Vegetative Vigor of Non

- Target Terrestrial Plants (Tier I/II): Lab Project Number: 000127. Unpublished study prepared by ABC Labs., Inc. 40 p.

45360610 Milazzo, D. (1993) XDE

- 795: The Toxicit y to the Green Alga Selenastrum capricornutum Printz: Lab Project Number: DECO

- ES

- 2606. Unpublished study prepared by The Dow Chemical Co. 32 p.
123

- 2 Aquatic plant growth

MRID Citation Reference

45360609 Mallett, M. (1999) The Toxicity of 3

- Hydroxy

- Quinoxyfen to the Freshwater Unicellular Green Alga Selenastrum capricornutum: Lab Project Number: GHE

- T

- 902. Unpublished study prepared by CEM Analytical Services Ltd. 65 p.

45360611 Kirk, H.; Gilles, M. (2000) 5,7

- Dichloro

- 4

- (1H)

- Quinoline (DCHQ): Growth Inhibition Test with the Freshwater Green Alga, Selenastrum capricornutum Printz: Lab Project Number: 001140. Unpublished study prepared by The Dow Chemical Co. 23 p.

45360612 Kirk, H.; Gilles, M.; McClymont, E. et al. (2000) Effects of Quinoxyfen (DE

- 795) on the Growth of the Aquatic Plant, Duckweed, Lemna gibba L. G

- 3: Lab Project Number:

### 36 991225. Unpublished study prepared by The Dow Chemical Co. 37 p.

45360613 Kirk, H.; Gilles, M.; McClymont, E. et al. (2000) Effects of Quinoxyfen (DE

- 795) on the Growth of the Saltwater Diatom, Skeletonema costatum: Lab Project Number: 991226. Unpublished study prepared by The Dow Chemical Co. 37 p.

45360614 Kirk, H.; Gilles, M.; McClymont, E. et al. (2000) Effects of Quinoxyfen (DE

- 795) on the Growth of the Freshwater Bluegreen Alga, Anabaena flos

- aquae: Lab Project Number: 991227. Unpublished study prepared by The Dow Chemical Co. 36 p.

45360615 Kirk, H.; Gilles, M.; McClymont, E. et al. (2000) Effects of Quinoxyfen (DE

- 795) on the Growth of the Freshwater Diatom, Navicula pelliculosa: Lab Project Number: 991228. Unpublished study prepared by The Dow Chemical Co. 40 p.

141

- 1 Honey bee acute contact

MRID Citation Reference

45360616 Hoxter, K.; Bernard, W.; Smith, G. (1992) XDE

- 795 Fungicide: An Acute Contact Toxicity Study with the Honey Bee: Lab Project Number: 103

- 380C: ES

- 2542. Unpublished study prepared by Wildlife International Ltd. 21 p.

45360617 Palmer, S.; Beavers, J. (1993) XDE

- 795 Fungicide: An Acute Contact Toxicity Study with the Honey Bee: Lab Project Number: 103

- 401D: ES

- 2562. Unpublished study prepared by Wildlife International Ltd. 21 p.

45360618 Palmer, S.; Beavers, J. (1993) XDE

- 795 F ungicide: A Dietary Toxicity Study with the Honey Bee: Lab Project Number: ES

- 2676: 103

- 400. Unpublished study prepared by Wildlife International Ltd. 19 p.

850.1400 Fish early

- life stage toxicity test

MRID Citation Reference

48102302 Hicks, S. (2005) Quinoxyfen: Early Life

- Stage Toxicity Test with the Sheepshead Minnow, Cyprinodon variegatus, under Flow

- Through Conditions. Project Number: 49241, 040426. Unpublished study prepared by ABC Laboratories, Inc. 77 p.

850.2100 Avian acute oral toxicity test

MRID Citation Reference

47783301 Hubbard, P. (2009) MTF

- 753: An Acute Oral Toxicity Study with the Zebra Finch (Poephila guttata). Project Number: 236/011209/ZF/LD/SUB236. Unpublished study prepared by Wildlife International, Ltd. 11 p.
850.2300 Avian reproduction test

MRID Citation Reference

47682501 Temple, D. (2007) 2

- Oxo

- Quinoxyfen Metabolite: A Reproduction Study with the Mallard. Project Number: 379/031607/MR/100P/4. Unpublished study prepared by Wildlife International, Ltd. 16 p.

850.4400 Aquatic plant toxicity test using Lemna spp. Tiers I and II

### 37 MRID Citation Reference

48387901 Softcheck, K. (2010) Quinoxyfen

- 7

- Day Toxicity Test with Duckweed (Lemna gibba). Project Number: 11344019, 12550/6574. Unpublished study prepared by Smithers Viscient Laboratories. 70 p.

Non

- Guideline Study

MRID Citation Reference

45360426 Ward, T.; Kowaleski, P.; Boeri, R. (1993) Acute Toxicity of XDE

- 795 Fungicide to the Earthworm, Eisenia foetida: Lab Project Number: 85

- DO: ES

- 2584. Unpublished study prepared by T.R. Wilbury Laboratories, Inc. 23 p.

45360427 England, D.; Leak, T. (1996) Chronic Toxicity of (carbon 14)

- XDE

- 795 Technical to Chironomus riparius from Aqueous Application in a 27

- day Exposure with Sediment: Lab Project Number: 42535: GHE

- T

- 641R. Unpublished study prepared by ABC Laboratories, Inc. 7 0 p. {OPPTS 850.1790}

45360600 Dow AgroSciences LLC. (2001) Submission of Toxicity, Environmental Fate and Efficacy Data in Support of the Application for Registration of Quinoxyfen Technical, Quinoxyfen Manufacturing Use Concentrate and Quintec. Transmi ttal of 30 Studies.

### 38 Appendix B. Complete Summary of Toxicity Endpoints for Quinoxyfen and Degradates.

Table B1 . Toxicity Profile for Quinoxyfen.

Group Species (Common Name) Endpoint (Duration) Toxicity Value (Measured Effect) MRID (Study Classification) Aquatic Organisms

Freshwater Fish ¶ Oncorhynchus mykiss (Rainbow Trout) LC 50 (96 hours) 270 μg a.i./L (Mortality) 45360413 (Supplemental)
LC 50 (21 days) 73.4 μg a.i./L (Mortality) 45360415 (Supplemental) NOAEC (21 days) 22 μg a.i./L (Mortality and weight) Lepomis macrochirus (Bluegill Sunfish) LC 50 (96 hours) >280 μg a.i./L (Mortality) 45360414 (Supplemental)

Cyprinus carpio (Common Carp) LC 50 (96 hours) 410 μg a.i./L (Mortality) 45360416 (Supplemental) Pimephales

promelas (Fathead Minnow) NOAEC (28 days) 13 (Growth: length) 45360424 (Acceptable)

Freshwater Invertebrates Daphnia magna (Water Flea) EC 50 (48 hours) 83 μg a.i./L ‡ (Immobility) 45360417 (Acceptable)

NOAEC (21 days) 27.8 μg a.i./L (Growth; reproduction) 45360423 (Supplemental)

Chironomus riparius (Non

- Biting Midge) EC 50 ( 27 days ) >508 μg a.i./L 45360427 (Supplemental) NOAEC (27 days) 128 μg a.i./L (emergence)

Estuarine/ Marine Fish Cyprinodon variegatus (Sheepshead

minnow) LC 50 (96 hours) >168 μg a.i./L (Mortality) 45360420 (Supplemental)
NOAEC (39 days) 4.1 μg a.i./L (Growth; Survival) 48102302 (Acceptable)

Estuarine/

Marine Invertebrates Crassostrea virginica (Eastern Oyster) EC 50 (96 hours) 72 μg a.i./L (Shell Deposition) 45360421 (Acceptable)

Americamysis bahia (Mysid shrimp) LC 50 (96 hours) 74.3 μg a.i./L (Survival) 45360422 (Acceptable)
NOAEC (28 days) <0.91 μg a.i./L (Reproduction) 48102301 (Supplemental)

### 39 Group Species (Common Name) Endpoint (Duration) Toxicity Value (Measured Effect) MRID (Study Classification)

Vascular

Plants Lemna gibba (duckweed) EC 50 (14 Days) >35 μg a.i./L (Frond number) 48387901 (Acceptable) NOAEC (14 Days) 35 μg a.i./L (Frond number)

Nonvascular Plants Raphidocelis subcapitata (green algae) EC 50 (120 Hours) 51 μg a.i./L (Cell Density) 45360610 (Supplemental) NOAEC (120 hours) 6.36 μg a.i./L (Cell Density)

Navicula pelliculosa (freshwater diatom) EC 50 (120 Hours) 30 μg a.i./L (Cell Density) 45360615 (Acceptable) NOAEC (120 hours) 17.7 μg a.i./L (Cell Density)

Skeletonema

costatum (marine diatom) EC 50 (120 Hours) 130 μg a.i./L (Cell Density) 45360613 (Supplemental) NOAEC (120 hours) <54.6* μg a.i./L (Cell Density)

Anabaena flos

- aquae

(cyanobacterium) EC 50 (120 Hours) >1,240 μg a.i./L 45360614 (Acceptable) NOAEC (120 hours) 1,240 μg a.i./L
Terrestrial Organisms

Avian § Colinus virginianus (Northern Bobwhite Quail) LD 50 (14 days) >2,292 mg a.i./kg

- bw (Survival) 45360407 (Acceptable) LC 50 (8 days) >5,620 mg/kg

- diet (Survival) 45360409 (Acceptable)

NOAEC 483 mg/kg

- diet (live 3

- week embryos/viable embryos 45360411 (Acceptable)

Anas platyrhynchos (Mallard Duck) LC 50 (8 days) >5,620 mg/kg

- diet (Survival) 45360410 (Acceptable)

NOAEC (27 weeks) 465 mg a.i./kg

- diet † (numbers of live/viable embryos and hatchling survival/eggs set) 45360412 (Supplemental)

Mammals Rattus norvegicus (Laboratory Rat) LD 50 >5,000 mg a.i./kg

- bw 45360616 (Acceptable)

NOAEL 20 mg a.i./kg

- bw 400 mg a.i./kg

- diet 45360522 (Acceptable)

Terrestrial Invertebrates Apis mellifera (European Honeybee) LD 50 (46 hours) >25 μg/bee 45360616 (Acceptable) LD 50 (48 hours) >100 μg/bee 45360617 (Acceptable)

### 40 Group Species (Common Name) Endpoint (Duration) Toxicity Value (Measured Effect) MRID (Study Classification)
LD 50 (48 hours) >1,000 μg/bee 45360618 (Supplemental) Eisenia fetida (Earthworm) L C 50 ( 14 days ) >923 mg/kg 45360426 (Supplemental)

Plants Dicots EC 25 0.366 lbs a.i./A (plant weight)

45360607 (Acceptable) NOAEC 0.064 lbs a.i./A (plant weight)

Monocots EC 25 >0.5 lbs a.i./A (no effects at highest concentration tested)

NOAEC 0.5 lbs a.i./A (no effects at highest concentration tested) * EC 05 = 5.6 μg a.i./L † In a memo date May 8, 2006 (DP Barcode D328427), the NOAEC for this study was changed

from <292 to 465 mg a.i./kg

- diet. ‡ Previous risk assessments used the LC 50 value from this study of 91 μg a.i./L, however, the EC 50

based on immobility is more appropria te for risk assessment since immobile daphnids are considered to be dead. § Birds are surrogates for terrestrial

- phase amphibians and reptiles. ¶ Freshwater are surrogates for aquatic

- phase amphibians



### Table B2. Summary of Degradate Toxicity Data

Group Species Endpoint (Duration) Toxicity Value (Measured Effect) MRID (Study Classification) DCHQ

Freshwater Invertebrates Daphnia magna EC 50 (48 Hours) >500 μg a.i./L 45360419 (Supplemental)

Nonvascular Plants Raphidocelis subcapitata (green algae) EC 25 (96 Hours) >500 μg a.i./L 45360611 (Supplemental) NOAEC (96 Hours) 500 μg a.i./L

3

- OH Quinoxyfen

Freshwater Invertebrates Daphnia magna EC 50 (48 Hours) >500 μg a.i./L 45360418 (Supplemental) 2

- oxo Quinoxyfen

Avian Anas platyrhynchos NOAEC 243 mg a.i./kg

- diet 489918

- 01 (Acceptable)

### 41 Appendix C . Results from the Screening Tool for Inhalation Risk Assessment (STIR)

### 42 Appendix D

. Results from Screening Imbibition Program (SIP)

### 43 Appendix E

. 

### Data Call

- In Justifi cation Tables

Study Title: Honeybee Larval Toxicity Study Guideline Number: Non

- guideline Test Substance: Quinoxyfen

— TGAI Rationale for Requiring the Data Although quinoxyfen is practically non

- toxic to adult worker bees on an acute contact exposure basis, a larval toxicity study is needed to determine the toxicity of the compound to developing brood. This study is part of EFED’s current screening level process for determining potential effects to terrestrial invertebrates. Therefore, a non

- guideline honeybee larval toxicity study is recommended. The registrant should submit a proposed protocol for review and approval by EFED prior to initiation of the study. Practical Utility of the Data How will the data be used? Data will be used to assess risk to non

- target listed and no n

- listed terrestrial invertebrate species. This study would allow the Agency to refine the screening

- level hazard assessment for beneficial terrestrial invertebrates. The effects data will be used to determine the potential for adverse effects on benefici al terrestrial invertebrates through direct effects on larval bees.

How could the data impact the Agency’s future decision

- making? EPA is required by section 7(a)(2) of the Endangered Species Act (ESA) to ensure that any action it authorizes or takes “... is not likely to jeopardize the continued existence of any endangered or threatened species or result in the destruction or adverse modification of critical habitat ” and “ to use the best scientific data available ” in carrying out this obligation. The data EPA intends to call in are necessary to inform the determination required by ESA as to whether continued registration of a pesticide is or is not likely to jeopardize the species or its designated critical habitat. The lack of these data will limit the fle xibility that the Agency has in coming into compliance with ESA and could result in use restrictions that are unnecessarily severe. In addition, the lack of these data may result in an uncertain assumed risk and potential mitigation of quinoxyfen formulati ons under FIFRA.

Study Title: Whole sediment chronic freshwater and/or marine invertebrate (3 Studies) Guideline Number: Agency

- wide Guideline Test Substance: Quinoxyfen

— TGAI Rationale for Requiring the Data The use pattern, chemical properties, estimated exposure, and toxicity profile of quinoxyfen indicate need for chronic (life cycle) sediment toxicity tests to fully evaluate potential risks to benthic invertebrates. These sediment toxicity studies include two freshwater species (the midge, Ch ironomus dilutus and the amphipod, Hyalella azteca ) and one saltwater species (the amphipod, Leptocheirus plumulosus ). Multiple species are being recommended in order to account for differential sensitivity and exposure potential of benthic invertebrates to quinoxyfen. This recommendation is being made because some K OC 

### and log K ow 

### values in submitted fate studies

were above the thresholds of 1,000 and 3.0, respectively

. The registrant should submit a proposed protocol for review and approval by EFED prior to initiation of the study.

(Note: As an alternative to the conduct of three chronic (life cycle) sediment toxicit y tests, EFED

### 44 would also consider a tiered testing approach for sediment toxicity testing. In this approach, sediment toxicity testing would first be conducted with the aforementioned species using the 10

- d (subchronic) sediment toxicity test guidelines ( OSCPP 850.1735 6 

### and 850.1740 7 

### ). Then, pending a comparison of estimated environmental concentrations (EEC) in sediment and pore water with toxicity results from the 10

- d sediment toxicity studies, the need for one or more chronic sediment toxicity studies would be determined. This tiered testing approach has the potential advantage of reducing the number of chronic (life cycle) studies that would be needed when results of the 10

- d (subchronic) tests in conjunction with sediment EECs indicate chronic testi ng is not likely to alter risk assessment conclusions. In some cases, however, this tiered testing approach may result in the conduct of both a 10

- d (subchronic) and a chronic (life cycle) study. If the tiered test approach described above is not preferre d, then chronic life

- cycle sediment toxicity studies be carried out on the three preferred species, C. dilutus

, H. azteca , and L. plumulosus .) Practical Utility of the Data How will the data be used? Data from sediment toxicity studies will be used to es timate potential risks to benthic organisms associated with uses of quinoxyfen . The data will reduce uncertainties associated with the current risk assessment for benthic species and will improve our understanding of the potential effects of quinoxyfen on aquatic ecosystems.

How could the data impact the Agency’s future decision

- making? If the data indicates that registered quinoxyfen uses may pose a risk of adverse effects to non

target benthic organisms above the Agency Level of Concern, the Agency may explore decision options to mitigate this risk. The lack of these data will limit the flexibility the Agency and registrants have in coming into compliance with the Endangered Species Act, and could result in use restrictions for quinoxyfen which may othe rwise be avoided, or which are unnecessarily

severe.

6 USEPA. 1996. http://www.epa.gov/opptsmnt/pubs/frs/publications/OPPTS_Harmonized/850_Ecological_Effects_Test_Gu idelines/Drafts/850

- 1735.pdf
7 USEPA. 1996. http://www.epa.gov/opptsmnt/pubs/frs/publications/OPPTS_Harmonized/850_Ecological_Effects_Test_Gu idelines/Drafts/850

- 1740.pdf