UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON D.C., 20460

OFFICE OF
CHEMICAL SAFETY AND
POLLUTION PREVENTION



### MEMORANDUM

DATE:

SUBJECT:

TO:

THROUGH:

FROM:

PEER REVIEW: November 24,2014

Registration Review- Preliminary Problem Formulation for the Ecological Risk Assessment and Drinking Water Exposure Assessment to
be conducted for Flonicamid (PC Code 128016; DP Barcode 421510)

Ricardo Jones, Chemical Review Manager

Neil Anderson, Chief

Risk Management and Implementation Branch 1

Pesticide Reevaluation Division (7508P)

Dana Spatz, Chief

# ~ Environmental Risk Branch 3

## ......;;;;::ot::::::-:-:1--~ Environmental Fate and Effects Division (7507P)

Colleen M. Rossmeisl, DVM, Biologis

Environmental Risk Branch 3

Environmental Fate and Effects Division (7507P)

Melissa Panger, PhD., Senior Scientist

James Hetrick, PhD., Senior Science**Advis<»'-__..;~·.....,.,** 

### Rosanna Louie-Juzwiak, RAPL

Environmental Risk Branch 3

Environmental Fate and Effects Division (7507P) 1 

### r(z.-l.f/ltf 

# ,-A 11/z. 'f 

# /If

L 

## 11/2.4 

# IN

The Environmental Fate and Effects Division (EFED) has completed the preliminary problem

formulation (attached) for the ecological risk and drinking water exposure assessments to be

conducted as part of the Registration Review of the insecticide flonicamid (PC Code 1280 16).

This document is intended to provide an overview of what is currently known regarding the

environmental fate and ecological effects associated with flonicamid and its degradation products, and outlines uncertainties regarding attributes of the parent compound and its

transformation products. It describes the preliminary ecological risk hypothesis and the processes that will be used during the completion of the preliminary ecological risk assessment in support
of Registration Review.

### 2

As noted in Section 5, the database for environmental fate and transport for flonicamid is
sufficie nt for risk assessment such that no additional data are anticipated to be needed at this
time

, with the exception of analytical test methods for water. With regard to the ecological
eff ects database, additional studies are needed for the registration review risk assessment, including pa sserine and honey bee toxicity studies (both according to new guidelines), aquatic
invertebr ate toxicity, and terrestrial plant toxicity studies.

Ba sed on the analysis completed in the problem formulation process, it is anticipated the registration review for the environmental fate and effects division will focus largely on the data uncertainties for passerines and terrestrial plants and those surrounding the unique mechanism of

ac tion and delayed mortality concerns with flonicamid, particularly for invertebrates. Several risk assessments have been conducted in the past years and have found no exceedances of levels
of conc ern (LOCs) for other taxa.

### 3

INTRODUCTION

Flonicamid is an insecti ci de registered for use on numerous terrestrial food crops and ornamentals. Its registered end use products include water dispersible granules and soluble concentrates/solids. Flonicamid is a member of the pyridinecarboxamide class of chemicals and controls pests b y contact and ingestion by provok ing rapid and irreversible feeding cessation.
The mechanism of action of flonicamid has not been widely investigated, but the class of

c hemistry has been described as an “A

- type potassium channel active.” 1 

### According to the registrant, there is no known cross-resistance of flonicamid to organophosphates, carbamates, pyrethroids, or neonicotinoids. Flonicamid is effective against both immature and adult stages of sensitive insects including aphids, thrips, whiteflies and mealybugs.

The chemical structure of flonicamid and several chemical identifiers are provided in Table 1

.

Table 1. Flonicamid Chemical Identifiers

Chemical Name N

- (cyanomethyl)

- 4

- (trifluoromethyl)

- 3

- pyridinecarboxamide

Chemical Structure

Chemical Abstracts Service (CAS) Registry Number 158062

- 67

- 0

Smiles Code C1=CN=CC(=C1C(F)(F)F)C(=O)NCC#N 1

1 CSID:8010234, http://www.chemspider.com/Chemical-Structure.8010234.html (accessed 12:34, Aug 25, 2014)



### An overview of the registered uses of flonicamid is provided in Tab le 2. Note that the application rates included on the currently registered labels are on a per season/crop cycle basis.
The number

of applications of flonicamid that can be applied per calendar year for a given use is not explicitly stated on many of the current labels. As such, several of the currently registered uses may result in multiple seasonal applications of flonicamid per year.

1 Joost, H., C. Staetz, B. Black, J. Hayashi, L. Kinne, G. Kelly, and K. Treacy (FMC Corporation). 2006.
FLONICAMID - A NOVEL MODE OF ACTION FOR PIERCING SUCKING INSECTS. Beltwide Cotton Conferences, San Antonio, Texas. pp. 1583- 1590.

### 4

Table 2. Currently Registered Flonicamid End-Use Products.

FORMULATION EPA REG. NO. % ACTIVE
INGREDIENT METHODS OF

APPLICATION USE RESTRICTIONS

F1785GH 50WG 279

- 3264 50% by weight Ground Spray - Use only for pest control of ornamental

plants in greenhouses and interiorscapes.

- Do not apply to food crops (fruits, nuts, or vegetables).

F1785N 50WG 279

- 3277 50% by weight Ground Spray - Use only for pest control of ornamental

plants in greenhouses and interiorscapes.

- Do not apply to food crops (fruits, nuts, or vegetables).

F6305 WDG 279

- 3333

RESTRICTED

USE 23.3% by weight

(also contains

6.7% zeta

cypermethrin) Ground

Aerial Chemigation - Do not use this product in greenhouses.

- Do not use this product in home gardens.

- Do not apply directly to water, to areas where surface water is present or to

intertidal areas below the mean high water

mark.

- Do not apply when weather conditions
favor drift from treated areas. Drift and runoff from treated areas may be hazardous to aquatic organisms in neighboring areas.

Flonicamid 50SG 279

- 3287 50% by weight Ground Spray - Do not apply to food crops (fruits, nuts or

vegetables).

- Do not apply to home gardens, home greenhouses or in residential settings.

- Do not apply this product through any type of irrigation system.

- Limited to use on ornamental plant materials managed by pro fessionals and grown within common areas of commercial, industrial and institutional buildings.

Flonicamid 50 WG 71512

- 9

RESTRICTED

USE 50% by weight Ground

Aerial Chemigation - Do not use this product in home gardens.

- Risk of exposure to sensitive aquatic areas can be reduced by avoiding applications when wind direction is toward the aquatic

area.

- Do not cultivate within 10 feet of the aquatic area so as to allow growth of a vegetative filter strip.

- Do not apply by ground equipment within 25 feet, or by air within 150 feet of lakes

, reservoirs, rivers, permanent streams,
marshes or natural ponds, estuaries, and commercial fish farm ponds.

- Increase the buffer zone to 450 feet when ultra low volume (ULV) applications are
made. BeleafTM 50SG 71512

- 1 0

71512

- 7 (RESTRICTED USE), 71512

- 14 Technical grade (for manufacture only)

### 5

Flonicamid was first registered in 2003. Based on the BEAD SLUA report, between 2004

– 2012

, the crop with the highest use (in pounds a.i. applied per year) is cotton with 10,000 average pounds used per year. The next highest usage crops were potatoes (3,000 average pounds per year) then alfalfa, celery and lettuce with 1,000 pounds used each. The maximum sing le application rate ranges from 0.089 to 0.268 lb a.i./acre with ornamentals having the hig hest application rate. Registered uses and applicable rates are further outlined in Tab le 3.

### 6

Table 3. Registered Flonicamid Uses and Application Rates

Crop/SiteResidentialAgriculturalForestry (Timing)

and Application Type Maximum

Single Application Rate by
Formulation (lb a.i./A) Maximum

Application Rate a Maximum Application

NumberPHI (days)MRI (days)GeographicRestrictions

Comments

Per Year
lb a.i./A Per CC

lb a.i./A Per

Year Per

CC

Alfalfa (grown for seed)  (Foliar ) Aerial, Ground, Chemigation 0.089 NS 0.178 NS 2 NS 7 AZ, CA, CO, ID, MT, NM (Only

Dona Ana
and Luna Counties), NV, OR, UT, WA,

WY AZ08004,

CA080018,CA140006, CO090005, ID070014, MT09003, NV070007, OR070023, UT070007, WA070013, WY080008;
Must be labeled “Not for

human or animal consumption”, 71512

- 10

Cucurbit Vegetables (Group 9) b  (Foliar) Aerial, Ground, Chemigation 0.089 NS 0.267 NS 3 0 7 None 71512

- 10

, 71512

- 9

F ruiting

V egetables (E xcept
C ucurbits ) c  (Foliar) Aerial, Ground, Chemigation 0.089 NS 0.267 NS 3 0 7 None 71512

- 10

0.133 NS 0.267 NS 2 0 7 None 71512

- 9

### 7

Crop/SiteResidentialAgriculturalForestry (Timing)

and Application Type Maximum

Single Application Rate by
Formulation (lb a.i./A) Maximum

Application Rate a Maximum Application

NumberPHI (days)MRI (days)GeographicRestrictions

Comments

Per Year
lb a.i./A Per CC

lb a.i./A Per

Year Per

CC

Hops  (Foliar) Aerial, Ground, Chemigation 0.089 NS 0.267 NS 3 10 7 None 71512

- 10

Leafy Vegetables (except Brassica) d  (Foliar) Aerial, Ground, Chemigation 0.089 NS 0.267 NS 3 10 7 None 71512

- 10

T uberous and
Corm Vegetables e  (Foliar) Aerial, Ground, Chemigation 0.089 NS 0.267 NS 3 7 7 None 71512

- 10

Root Vegetables (except Sugar Beets) f  (Foliar) Aerial, Ground, Chemigation 0.089 NS 0.267 NS 3 3 7 None 71512

- 10

Pome Fruit g  (Foliar) Aerial, Ground, Chemigation 0.089 NS 0.267 NS 3 21 7 None 71512

- 10

Stone Fruit h  (Foliar) Aerial, Ground, Chemigation 0.089 NS 0.267 NS 3 14 7 None 71512

- 10

### 8

Crop/SiteResidentialAgriculturalForestry (Timing)

and Application Type Maximum

Single Application Rate by
Formulation (lb a.i./A) Maximum

Application Rate a Maximum Application

NumberPHI (days)MRI (days)GeographicRestrictions

Comments

Per Year
lb a.i./A Per CC

lb a.i./A Per

Year Per

CC

Clover (grown for seed)  (Foliar) Aerial, Ground, Chemigation 0.089 NS 0.178 NS 2 NS 7 ID 71512

- 10, ID070014

H ead and Stem
Brassica (Cole)

and Mustard
Greens i  (Foliar) Aerial, Ground, Chemigation 0.089 NS 0.267 NS 3 0 7 None 71512

- 9, 71512

- 10

Cotton  (Foliar) Aerial, Ground, Chemigation 0.089 NS 0.267 NS 3 30 7 None 71512

- 10

Potato  (Foliar) Aerial, Ground, Chemigation 0.089 NS 0.267 NS 3 7 7 None 71512

- 10

Low Growing Berry Subgroup

j  (Foliar) Aerial, Ground, Chemigation 0.089 0.267 NS 3 NS 0 7 None 71512

- 9, 71512

- 10

Rapeseed subgroup k  (Foliar) Aerial, Ground, Chemigation 0.089 0.267 NS 3 NS 7 7 None 71512

- 9, 71512

- 10

### 9

Crop/SiteResidentialAgriculturalForestry (Timing)

and Application Type Maximum

Single Application Rate by
Formulation (lb a.i./A) Maximum

Application Rate a Maximum Application

NumberPHI (days)MRI (days)GeographicRestrictions

Comments

Per Year
lb a.i./A Per CC

lb a.i./A Per

Year Per

CC

Carrot tops  (Foliar) Aerial,
Ground 0.089 NS 0.35 NS 4 NS 7 None CA090001 (1)

Greenhouse
Cucumber  (Foliar / soil

media
treatment/wh en needed)
Ground 0.133 NS NS NS 2 0 7 None 71512

- 9, 71512

- 10

Mint/Peppermi nt/Spearmint  (Foliar) Aerial, Ground, Chemigation 0.089 NS 0. 267 NS 3 7 14 None 71512

- 9, 71512

- 10

Ornamentals (unspecified)  (Foliar)
Ground 0.134 NS 0.267 NS 2 l NS 7 None 279

- 3287

0.268 NS 0.267 NS 1 l NS 7 None 279

- 3277

NS NS NS NS NS 7 None 279

- 3264

N o maximum application rate is specified on label; Label states to reapply as necessary every 7

- 28 days

### 10

Crop/SiteResidentialAgriculturalForestry (Timing)

and Application Type Maximum

Single Application Rate by
Formulation (lb a.i./A) Maximum

Application Rate a Maximum Application

NumberPHI (days)MRI (days)GeographicRestrictions

Comments

Per Year
lb a.i./A Per CC

lb a.i./A Per

Year Per

CC

Greenhouse

Tomato  (Foliar ) Ground, Chemigation 0.133 NS NS NS 2 0 7 None 71512

- 9, 71512

- 10

Tree Nuts  (Foliar) Aerial, Ground, Chemigation 0.089 NS 0. 267 NS 3 40 7 None 71512

- 9, 71512

- 10

a The number of applications of flonicamid that can be applied per calendar year for a given use is not explicitly stated on ma ny of the current labels. As such, several of the currently registered uses may result in multiple seasonal applications of flonicamid per year and this would be reflected when modeling total product usage for the year

.

b Curcubit

- Balsam apple, balsam pear, bitter melon, Chayote, Chinese cucumber, Chinese waxgourd (Chinese preservi ng melon), Citron melon; Cucumber, Gherkin, Gourd, edible (includes: hyotan, cucuzza, hechima and Chinese okra); Muskmelon (includes: true cantaloupe, cantaloup e, casaba, crenshaw melon, golden pershaw melon, honeydew melon, honey balls, mango melon, Persi an melon, pineapple melon, Santa Claus melon, and snake melon), Pumpkin, Squash, summer (includes: crookneck squash, scallop squash, straightneck squash, vegetable marrow, zucchini), Watermelon, Winter Squash (inc ludes butternut squash, calabaza,

hubbard s quash, acorn squash, spaghetti squash)

c Fruiting Vegetables

- Eggplant; Groundcherry, Okra, Pepino, Pepper (includes: bell pepper, chili pepper, cooking pepper, pimento, sweet pepper), To matillo,

Tomato.

d Leafy Vegetables (except Brassica)

- Amaranth ( leafy amaranth, Chinese spinach, tampala), Arugula (rouquette), Cardoon, Celery, Chinese Celery, Celtuce, Chervil, Chrysanthemum (edible leaved and garland), Corn salad, Cress (garden and upland), Dandelion, Dock (sorrel), Endive ( escarole), Florence fenne l, Lettuce (head and leaf). Orach, Parsley, Purslane (garden and winter), Radicchio (red chicory), Rhubarb, Spinach, Spinach (New Zealan d), Swiss chard, Vine spinach (Malabar and Indian)

e Tuberous

- Arracacha; Arrowroot; Chinese artichoke; Jerusalem artichoke; Edible canna; Casava (bitter and sweet); Chayote (root); Chufa; Oasheen; Ginger; Leren; Potato; Sweet potato; Tanier; Turmeric; Yam Bean; Yam (true).

f Root vegetables

- Beet, garden; Burdock, edible; Carrot; Celeriac; Chervil, turniprooted; Ch icory; Ginseng; Horseradish; Parsley, turnip

- rooted; Parsnip; Radish; Radish, oriental; Rutabaga; Salsify: Salsify, black; Salsify, Spanish; Skirret; Turnip.

g Pome fruits

- Apple, Crabapple. Loquat Mayhaw, Pear, Oriental Pear, Quince

### 11

Crop/SiteResidentialAgriculturalForestry (Timing)

and Application Type Maximum

Single Application Rate by
Formulation (lb a.i./A) Maximum

Application Rate a Maximum Application

NumberPHI (days)MRI (days)GeographicRestrictions

Comments

Per Year
lb a.i./A Per CC

lb a.i./A Per

Year Per

CC

h Stone Fruit

- Ap ricot, Cherry (sweet and tart), Nectarine, Peach, Plum (includes Chickasaw plum, Damson plum, and Japanese plum), Plumcot Pru ne (fresh)

i H ead and Stem Brassica and Mustard Greens

- Includes mustard greens and all members of Crop Subgroup 5A: Broccoli, Ch inese broccoli, Brussels sprouts, Cabbage, Chinese cabbage (napa), Chinese mustard cabbage, Cauliflower, Cavalo broccoli,

Kohlrabi

j Bearberry; bilberry; blueberry, lowbush; cloudberry; cranberry; lingonberry; muntries; partridgeberry; strawberry; cultiv ars, varieties, and/or hybrids of these

k Borage; crambe,; cuphea; echium; flax seed; gold of pleasure; hare's ear mustard; lesquerella; lunaria; meadowfoam; milkweed; mustard seed; oil radish; poppy seed; rapeseed; sesame; sweet rocket; cultivars, variet ies, and/or hybrids of these

l Maximum number of applications per cc not specified; number was calculated by maximum application rate per cc divided by maximum single application rate

### 12

1. PREVIOUS RISK ASSESS MENTS

Previous Ecological Assessments

In August 2003, EFED conducted a risk assessment to support the initial registration of
flonica mid for indoor greenhouse uses (DP Barcodes: 285425, 285447). Since the assessment applied only to indoor greenhouse use of flonicamid, EFED did not conduct a formal risk assessment. However, environmental fate and effects data were evaluated and uncertainties and
de ficiencies were identified that would need to be addressed prior to conducting a risk
assessment for outdoor uses.

In 2004, EFED completed a Section 3 ecological risk assessment for the use of flonicamid on numerous terrestrial food crops and ornamentals (DP Barcodes 298809, 301587, 306653, 308735, 308562). The 2004 assessment did not identify any significant risk to most non-target

aqu atic and terrestrial organisms, but expressed concern regarding flonicamid’s potential sublethal effects on honey bees.

In 2007, EFED completed a Section 3 ecological risk assessment for new uses on root vegetables, tuberous and corn vegetables, and hops (DP Barcodes 331071, 331027). The 2007 risk assessment suggested that threatened or endangered terrestrial invertebrates may be potentially at risk from flonicamid use, and found potential risks to all other terrestrial and aquatic species to be negligible.

In 2012, EFED completed a Section 3 ecological risk assessment for the use of flonicamid on
low -growing berries and rapeseed. No acute and/or chronic risk quotients (RQs) for listed or

non -listed birds, mammals, freshwater fish, estuarine/marine fish or freshwater invertebrate species exceed ed the Level of Concern (LOC). Additionally, no RQs for listed and non-listed plants exceeded the 

## LOC. C oncerns were raised for toxicity to honeybees and other non-target

terre strial invertebrates, as well as the lack of toxicity data for chronic exposure for

e stuarine/marine animals and passerine species.

In 2013, EFED completed an ecological risk assessment for a Section 3 use of flonicamid on

a lfalfa and c lov er g rown for s eed, f ruiting v egetables, m int, t ree n uts, and the e xpansion to the

f ull c rop g roup for p ome f ruit and s tone f

ruit

. No acute or chronic RQs for listed or non

- listed birds, mammals, freshwater fish, or freshwater invertebrate species exceed ed the LOC. Continued concern for toxicity to honeybees as well as data gaps for both honeybees and passerine species was discussed.

A summary of risk concerns based on the se previous assessments is summarized in Table 4

.

### 13

Table 4. Summary of Risk Concerns Identified for Flonicamid

Exposure
Basis Birds Mammals Terrestrial

Plants Terres

trial

Inverts. (honey

bee hazard) Fish Aquatic

Inverts Aquatic

Plants Ground

water
Contam

ination Persistence Degradates
of Concern

Acute No a No No Yes b No No No No No No Chronic No a No No No

a. Data not available for passerines at time of previous risk assessments
b. No exceedance s of LOCs, but significant risk concern was identified in previous assessments due to possible delayed mortality effects



### Previous Drinking Water Assessments

A drinking water assessment for flonicamid residues was conducted in 2013 [USEPA, 2013 2 

### ] using both a parent only exposure, and a total toxic residue (TTR) approach, which considers the parent compound and its major degradates of concern previously identified by HED, including TFNA, TFNG, TFNA- AM , TFNA-OH and TFNG

- AM

. The predicted concentrations of flonicamid total toxic residues, except cranberry, we re found to be lower than estimated drinking water concentrations (EDWC) in previous drinking water assessments. The EDWCs for cranberry had been previously estimated using the Tier 1 rice model, which does not account for
dil ution and degradation. Because flonicamid and its degradation products degrade rapidly in aerobic soil, the EDWCs for cranberry were considered highly conservative and greatly

ex aggerated the Tier 1 screening EDWCs (94.93 μ g/ L for single application and 285.44 μg/L for annual application rate) . EFED recommend ed using the EDWCs from PRZM-GW. The concentration of total toxic residues of flonicamid (flonicamid TTR) in ground water wa s predicted to not exceed 15.9 μg/L for the daily peak and 9.92 μg/L for the 30 year annual average. These concentrations we re associated with the proposed increased application rate of
0.133 lb a.i./A on fr

uiting vegetables based upon 2 applications per calendar year, which provides a more conservative estimate than the use of 0.267 lb a.i./A, the maximum application
rate f or ornamentals.

Clean Water Act Programs

Flonicamid is not identified as a cause of impairment for any water bodies listed as impaired
under se ction 303(d) of the Clean Water Act. Total Maximum Daily Load (TMDL) criteria have not been developed for flonicamid. Aquatic benchmarks have not been established for
floni camid ( http://www.epa.gov/oppefed1/ecorisk_ders/aquatic_life_benchmark.htm ). Any data submitted or otherwise located as part of the registration review process may be used to establish aquatic life benchmarks, if applicable.

2 USEPA. Drinking Water Assessment to Assess Flonicamid Use on Alfalfa and Clover Grown for Seed, Fruiting Vegetables, Mint, Tree Nuts, and the Expansion to the Full Crop Group for Pome Fruit and Stone Fruit. PC Code: 128016; DP Barcode: 408552, 408555, 412695

. June 23 , 20 13

.

### 14

2. ENVIRONMENTAL FATE AND TRANSPORT

Physical and Chemical Properties of Flonicamid

The ph ysicochemical properties of flonicamid are shown in Tab le 5 . Based on these properties alone, flonicamid is not expected to be volatile or to bioaccumulate.

Tab le 5. Selected P hysical/Chemical 

### Parameters of Flonicamid

Chemical name Property

Chemical Abstract Service number 158062

- 67

- 0 Empirical Formula C 9 H 6 F 3 N 3 O Molecular weight 229 g/mole Aqueous Solubility 5300 mg/L
Vapor Pressure ( 25  C ) 7.07X10

- 9 torr pKa 11.6

Octanol

- water partition coefficient (Kow at

30  C ) 1.9



### Environmental Fate Properties of Flonicamid

The chemical structure of flonicamid and its degradation products are provided in F igures 1 and
2

.

Figure 1. Chemical Structure of Flonicamid

Structure of N- (4 -Trifluoromethylnicotinoyl) glycine (TFNG)

### 15 Structure of 4-Trifluoromethylnicotinic acid (TFNA)



### Structure of 6-Hydroxy-4-trifluoromethyl nicotinic acid (TFNA- OH)

Struc ture of 4-Trifluoromethylnicotinamide (TFNA-AM)

Struc ture of N- (4 -Trifluo romethylnicotinoyl) glycinamide (TFNG-AM)

Figure 2 . Chemical Structure of Flonicamid Degradation Products

Floni camid applications can lead to surface water contamination through spray drift, runoff, sediment erosion and ground water contamination through leaching. Given the low Kd values for
flonic amid, it is anticipated that the sediment bound fraction would be low. Flonicamid rapidly degrades in soil to form five degradation products (TFNA, TFNG, TFNA- AM , TFNA-OH,
TFNG- AM ). Both flonicamid (K oc 

### = 11.2
- 20.7 ) and its degradation products are expected to be

ver y mobile in terrestrial and aquatic environments. Laboratory K oc 

### values for the degradation products were not calculated from submitted batch equilibrium studies due to the lack of sorption on the test soils. Flonicamid is stable to hydrolysis and photolysis under typical environmental
condit ions, but degrades rather quickly in aerobic environments (soil t 1⁄2 

### = 1.2

– 3.1 days; aquatic total system t 1⁄2 

### = 36

– 44 days), and more slowly under anaerobic conditions (t 1⁄2 

### = 161 days).

### 16

Although flonicamid and its degradation products are not persistent in soil, they exhibit low soil:water partitioning coefficients to promote leaching into ground water. Detailed summaries
of the available environmental fate data for flonicamid are available in the 2004 Section 3 ecological risk assessment for the use of flonicamid on terrestrial food crops and ornamentals (DP Barcodes 298809, 301587, 306653, 308735, 308562).

Flonicamid is expected to be very mobile in the environment. The soil to water partitioning

coe fficients (K d 

### ) derived from the four soils studied, at two different concentrations, ranged from
0.09 to 0.5, with an average value of 0.25. Table 6 summarizes the environmental fate properties of flonicamid.

Table 6. Chemical Properties and Environmental Fate Parameters of Flonicamid

Parameter Value Description Study Status Source (MRID)

Persistence

Hydrolysis half

- life pH 4: stable (50  C ) pH 5: stable (25  C,

50  C) pH 7: stable (25  C, 50  C) pH 9: 204, 18, 12 days at

25  C, 40  C , 50  C Acceptable 45656801

Aqueous photolysis half

- life S table pH 7 at 23  C Acceptable 45656802

Soil photolysis half

- life 77 days Loamy sand soil (12 hour light/dark cycle) Acceptable 45656803

Aerobic soil metabolism

half

- life 3.1 Loamy sand soil Supplemental 45656804

45854817

1.2 Loamy sand soil Acceptable 45854817

1.2 Sandy loam soil

1.9 Sand soil

Anaerobic aquatic

metabolism half

- life (total system) 161 days HPLC grade water / soil (not characterized) from
Ohio (total system) Acceptable 45854821

46222701

Aerobic aquatic metabolism

half

- life (total system) 36 days Pond water/silty clay

loam from
Switzerland Acceptable 45854822

44 days River water/sandy

loam sediment from
Switzerland

Mobility

Adsorption/Desorption

– Kd 0.09 OK loamy sand Acceptable 45656805

0.3 OK sandy loam

### 17

Parameter Value Description Study Status Source (MRID)

0.2 German sandy loam

0.1 OH loamy sand

Terrestrial field Dissipation

half life (total system) 3 days Bare ground/sand soil Ephrata, WA Acceptable 4585 4906

4 days Bare ground/sandy

loam soil Madera, CA Acceptable 4585 4907

10 days Bare ground/silt loam

soil Northwood, ND Acceptable 4585 4908

10 days Bare ground/loamy

sand soil Garner, NC Acceptable 4585 4909



### Transformation Products

Like the parent compound, flonicamid’s degradates ( TFNA, TFNG, TFNA-AM, TFNA- OH

, TFNG-AM) rapidly degrade in aerobic environments, and more slowly under anaerobic conditions. Under normal environmental conditions, flonicamid degrades into three major (TF NA, TFNG-AM and TFNA-OH) and two minor (TFNG and TFNA-AM) degradates. Flonicamid degrades by hydrolytic cleavage of the cyano and amide side chains to 4- trifluoromethylnicotinic acid (TFNA) and N- (4 -trifluoromethyl nicotinoyl)-glycinamide (TFNGAM), respectively. TFNA degrades rapidly to 6-hydroxy-4-trifluoromethylnicotinic acid (TF NA-OH). TFNG-AM degrades rapidly to N- (4 -trifluor omethyl nicotinoyl)glycine (TFNG), which, in turn, degrades mainly to TFNA, with some intermediary transformation into 4- trifluoromethyl nicotinamide (TFNA-AM). These transformations occur under aerobic conditions, with degradate half-lives ranging from 1 to 3 days. Almost complete conversion to carbon dioxide and soil-bound residues occurs within 30 days under aerobic conditions in soil.

Under anaerobic conditions, flonicamid degrades by hydrolytic cleavage of the cyano and amide side chains into 4-trifluoromethylnicotinic acid (TFNA). TFNA is stable under anaerobic
conditions. Concentrations of TFNA were at a maximum after flonicamid was allowed to degrade in soil for one year under anaerobic conditions. Table 7 summarizes transformation product formation and associated study types and MRIDs. More detailed information on the transformation products can be found in Appendix A

. Field Dissipation

### 18

Table 7. Summary of Flonicamid Transformation Products from Environmental Fate Testing
Conduc ted on the Parent Flonicamid.

Degradate Name Maximum
% of Applied MRID # Study Type

6

- Hydroxy

- 4

- trifluoromethylnicotinic acid (TFNA

- OH) 21% 45656804 aerobic soil metabolism

7.6% 45854822 aerobic aquatic
metabolism

4

- Trifluoromethylnicotinic acid (TFNA) 36% 45656804 aerobic soil metabolism

18% 45854822 aerobic aquatic
metabolism

76%* 45854821 anaerobic aquatic
metabolism

N

- (4

- Trifluoromethylnicotinoyl) glycine (TFNG)

2.0%* 45656803 photolysis in soil

3.9% 45854818 aerobic soil metabolism

3.7% 45854822 aerobic aquatic
metabolism

N

- (4

- Trifluoromethylnicotinoyl) glycinamide (TFNG

- AM)

16% 45656803 photolysis in soil

10% 45854818 aerobic soil metabolism

4

- Trifluoromethylnicotinamide (TFNA

- AM) 3.4% 45656801 hydrolysis

3.0% 45656802 photolysis in water

5.0%* 45656803 photolysis in soil

7.6% 45854818 aerobic soil metabolism

1.4% 45854822 aerobic aquatic

metabolism
*Maximum % of applied reported at study termination; amounts may have continued to increase with time

Bold indicates maximum % formation percentage of degradate



### Submitted mobility data for the five flonicamid degradation products indicate even greater
environmen tal mobility than that of the parent compound. Individual soil to water partitioning coefficients (K d 

### ) for the five degradates ranged from 0.0 to 0.20. Table 8 summarizes the aerobic metabolism and mobility of the flonicamid transformation products.

### 19

Table 8 . Summary of Aerobic Metabolism Half-lives and Soil to Water Partitioning Coefficients
of Flonicamid Transformation Products.

Flonicamid Degradation

Product Soil Type Soil/Water Partitioning
Coefficient (K d ) Half

Life Study

MRID

TFNA

- OH (6

- Hydroxy

- 4

- trifluoromethyl nicotinic acid) Loamy sand N/A 1.5 days 45863810

Sandy loam N/A 1.9 days 45863810

Sand N/A 2.6 days 45863810

median 0.03 mL/g N/A 45854903

TFNA (4

- Trifluoromethylnicotinic acid) Loamy sand N/A 0.5 days 45863808

Sandy loam N/A 0.3 days 45863808

Sand N/A 0.5 days 45863808

median 0.01 mL/g N/A 45854901

TFNG (N

- (4

- Trifluoromethylnicotinoyl) glycine) Loamy sand N/A 0.1 days 45863809

Sandy loam N/A 0.2 days 45863809

Sand N/A 1.6 days 45863809

median 0.02 mL/g N/A 45854902

TFNG

- AM (N

- (4

- Trifluoromethylnicotinoyl) glycinamide) Loamy sand N/A 0.25 days 45854820

Sandy loam N/A 0.3 days 45854820

Sand N/A 1.0 days 45854820

median 0.12 mL/g N/A 45854905

TFNA

- AM (4

- Trifluoromethylnicotinamide) Loamy sand N/A 1.2 days 45854819

Sandy loam N/A 1.0 days 45854819

Sand N/A 2.3 days 45854819

median 0.11 mL/g N/A 45854904



### 3. RECEPTORS

Tables 9 and 10 provide a summary of the aquatic and terrestrial toxicity data, respectively, and
the most sensitive surrogate species tested to characterize the potential acute and chronic ecological effects of flonicamid.

### 20

Table 9. Toxicological Endpoints for Aquatic Species

Assessment Endpoint Measures of

Effect Species Toxicity
Value* Endpoint Reference

Freshwater fish : Freshwater

fish acute

LC 50 Rainbow trout LC 50 : >98

mg a.i./L Lethality MRID 45656808

Survival and reproduction of
individuals and
communities 96

- h (Oncorhynchus mykiss) Supplemental

M inor deviations in water chemistry and
fish acclimation time

No more than slightly toxic †

Freshwater

fish acute

LC 50 Bluegill

Sunfish LC 50 : >99

mg a.i./L Lethality MRID 45656807

96

- h (Lepomis

macrochirus) Supplemental

M inor deviations in water chemistry and
fish acclimation time

No more than slightly toxic †

Freshwater fish early life

stage NOAEC Fathead

Minnow NOAEC:

9.5 mg
a.i./L Reproduction; growth MRID 45854914

( Pimephales promelas) LOAEC:

20 mg
a.i./L Acceptable

33

- day Terminal dry weight significantly lower in the 20 mg a.i./L treatment group

No treatment

- related effects on time to hatch, hatching
success, post

- hatch (larval) survival, clinical effects, terminal length, or terminal wet weights were observed

Freshwater
invertebrates : Freshwater

invertebrate

LC 50 Waterflea LC 50 : >99 mg a.i./L Lethality MRID 45656806

Survival and reproduction of
individuals and

communities 48

- h (Daphnia magna)
Static NOAEC:

99 mg
a.i./L Immobilization: No

immobilization occurred at 100 mg a.i./L flonicamid TGAI (98.7%) Supplemental

S everal minor guideline deviations in initial review;
Additional
discussion below

No more than slightly toxic†

### 21 Freshwater
invertebrate life cycle NOAEC Waterflea NOAEC: 3.0 mg
a.i./L Reproduction (fecundity):

significantly lower when

concentration > 6.08 mg
a.i./L MRID 45863812

(Daphnia magna) Supplemental

21

- day Static renewal

LOAEC: 6.1 mg
a.i./L Growth (body length):

significantly reduced when
nominal concentration > 12.5 mg a.i./L Treatments not
verified at all
concentrations ; Additional
discussion below

LC 50 : 42.1 mg a.i./L Lethality Slightly toxic †

Estuarine and
marine fish : Estuarine and

marine acute

LC 50 Sheepshead

minnow LC 50 :

>120 mg
a.i./L Lethality MRID 45854913

Survival and reproduction of
individuals and

communities 96

- h (Cyprinodon variegatus) Supplemental Fish weight too low

flow

- through Practically non

toxic †

Estuarine and marine fish early
life

- stage
NOAEC No Data

Estuarine and
marine
invertebrates : Estuarine and

marine
invertebrate

LC50 Eastern oyster LC 50 : > 128 mg
a.i./L Lethality MRID 45854911

(Crassostrea virginica) NOAEC:

71 mg
a.i./L Shell Growth

Acceptable
Survival and reproduction of
individuals and
communities 96

- h Flow

- through LOAEC: 128 mg
a.i./L Practically non

toxic †
Mysid LC 50 : >

121 mg
a.i./L Lethality MRID 45854912

(Americamysis bahia) NOEC: 44

mg a.i./L NOEC and LOEC were

based on 10% mortality at 69 mg a.i./L after 96 h and erratic swimming in up to 15% of the 69 mg a.i./L group and up to 33% of the 121 mg a.i./L group Acceptable

Flow

- through LOEC: 69

mg a.i./L Practically non

toxic †

Additional
discussion below

Estuarine and
marine
invertebrate life cycle NOAEC No Data

Aquatic plants : Non

- vascular Freshwater green algae EC 50 >

119 mg
a.i./L Cell density, biomass,

growth rate MRID 45854920

Standing crop or
biomass and growth Freshwater green

algae, cyanobacteria or
diatom EC 50 (Selenastrum

capricornutum) NOAEC:

119 mg
a.i./L No significant effects seen

for these endpoints Acceptable

Static renewal

96

- h/7

- day

### 22 Non

- vascular Freshwater

green algae EC 50 >

96.7 mg
a.i./L Cell density MRID 45656814

Freshwater green algae, cyanobacteria or
diatom EC 50 (Selenastrum

capricornutum) NOAEC:

43.8 mg
a.i./L A 14% reduction in

biomass was observed at
nominal concentration of 43.8 mg a.i./L Supplemental

Treatments not
verified at all
concentrations

72

- h

Vascular Duckweed EC 50 > 119 mg
a.i./L Frond number, occurrence

of curled fronds MRID 45854919

Freshwater EC50 (Lemna gibba) NOAEC: 7.3 mg
a.i./L Acceptable

96

- h/7

- day Static renewal LOAEC: 15 mg
a.i./L 21% reduction in frond

number and occurrence of curled fronds at 15 mg
a.i./L

– effects not dose

dependent

* Toxicity values in bold were used in Risk Quotient calculations.

† Based on EC 50 (mg/L): < 0.1 very highly toxic; 0.1

- 1 highly toxic; >1

- 10 moderately toxic; >10

- 100 slightly toxic; >100 practically nontoxic.



### Table 10. Toxicological Endpoints for Terrestrial Species

Assessment Endpoint Measures of

Effect Species Toxicity Value Endpoint Reference / Study
classification

Birds : Avian acute oral

LD 50 N orthern

Bobwhite Quail LD 50 : >2250 mg

a.i./kg

- bw Lethality MRID 46159701

Abundance (i.e., survival, reproduction, and growth) of
individuals and populations 14

- days (Colinus virginianus) NOAEL (lethal):

1350 mg a.i./kg

bw Acceptable

NOAEL (sublethal): 810 mg a.i./kg

- bw Body weight gain

significantly
reduced and food consumption significantly lower
for males at 1350 mg a.i./kg LOAEL: 1350 mg a.i./kg

- bw Practically non

toxic †

Avian sub

- acute dietary LC 50 N orthern

Bobwhite Quail LC 50 : >4613 mg

a.i./kg

- diet Lethality MRID 45656811

8

- days (Colinus

virginianus) NOAEC: <4613

mg a.i./kg

- diet Supplemental

Food consumption and body weight
reduced significantly at 4613 mg a.i./kg M inor deviations

from guideline requirements

Slightly toxic ∆

Mallard duck LC 50 : > 5037 mg

a.i./kg

- diet Lethality MRID 45656812

(Anas platyrhynchos) NOAEC: <5037

mg a.i./kg

- diet Acceptable

### 23

Assessment Endpoint Measures of

Effect Species Toxicity Value Endpoint Reference / Study
classification

LOAEC: 5037 mg a.i./kg

- diet Food consumption

and body weight
reduced significantly at 5037 mg a.i./kg Practically non

toxic ∆

Avian reproduction

NOAEL N orthern

Bobwhite Quail NOAEC: 1030

mg a.i./kg

- diet No significant

effects MRID 45854915

2

- generation (Colinus

virginianus) LOAEC: >1030

mg a.i./kg

- diet Acceptable

21

- wk

Mallard duck NOAEC: 415 mg a.i./kg

- diet Significant

reductions in mallard embryo viability and hatchability at 1030 mg a.i./kg MRID 45854916

(Anas platyrhynchos) LOAEC: 1030

mg a.i./kg

- diet Acceptable

Mammals : Mammalian acute

oral LD 50 Sprague

Dawley Rat ♂ LD 50 : 884 mg

a.i./kg

- bw Lethality MRID 45656707

Abundance (i.e., survival, reproduction, and growth) of
individuals and populations ♀ LD 50 : 1768 mg a.i./kg

- bw Acceptable

Slightly toxic †

Mammalian reproductive

NOAEL Wistar Rat NOAEC: 1800 mg a.i./kg

- diet No significant

effects on offspring body weight, anogenital distance, gross pathology, birth, live birth, viability, or
lactation indices. MRIDs 45854613,

45854612

2

- generation LOAEC: >1800 mg a.i./kg

- diet Acceptable

Significant effect on kidney weight at 300 mg a.i./kg but
this endpoint is not related to an apical endpoint and will
not be used in the ecological risk

assessment

Insect : Honey bee acute

contact LD 50 Honey bee LD 50 : >100  g a.i./bee Lethality of TGAI MRID 45656813

Survival of populations 48

- h 1 ( Apis mellifera ) NOAEL: <100

mg a.i./bee Acceptable
Uncertainties remain regarding adequacy of test
duration

Practically non

toxic §
Honey bee LD 50 : >51.1  g

a.i./bee Lethality of

Flonicamid 50WG MRID 45863813

### 24

Assessment Endpoint Measures of

Effect Species Toxicity Value Endpoint Reference / Study
classification (Apis mellifera) NOAEL: <51.1

 g a.i./bee Supplemental
Test duration not long enough; see discussion below

Practically non

toxic §
Honey bee acute
oral LD 50 Honey bee LD 50 : >60.5  g a.i./bee Lethality of TGAI MRID 45656813

96

- h 1 (Apis

mellifera) NOAEL: <6.4

 g a.i./bee Supplemental

Non

- guideline study

LOAEL: 6.4  g a.i./bee Practically non

toxic §
Honey bee LD 50 : >3.5  g

a.i./bee Lethality of

Flonicamid 50WG MRID 45863813

(Apis mellifera) NOAEL: <3.5

 g a.i./bee Significant

behavioral effects (coordination problems, apathy, nervousness) in all
treatment groups
after 24 hours Supplemental

–

for qualitative use only High variability
within and across

test treatment groups; t est duration not long enough; see discussion below

LOAEL: 3.5  g a.i./bee
Moderately toxic §
Terrestrial plants :

Seedling

emergence Dicots :

Cucumis sativus, Glycine max, Lycopersicon esculentum, Raphanus
sativus,

Brassica oleracea,

Daucus

carota,
Lactuca sativa

Monocots: Zea mays, Avena sativa,
Lolium

perenne, Allium cepa EC 25 : >0.134 lb

a.i./A No effects noted in

the study

Study n ot
conduc ted at
maximum application rate MRID 45854917

Survival and growth 21

- days NOAEC: 0.134
lb a.i./A Acceptable

Vegetative vigor

EC 25

EC 25 : >0.134 lb
a.i./A No effects noted in

the study

Study not

conducted at
maximum application rate MRID 45854918

16

- days NOAEC: 0.134
lb a.i./A Acceptable

* Toxicity values in bold were used in Risk Quotient calculations.

† Acute Oral (avian/mammal): Based on LD 50 (mg/kg) < 10 very highly toxic; 10

- 50 highly toxic; 51

- 500 moderately toxic;
501

- 2000 slightly toxic; >2000 practically nontoxic

∆ Acute Dietary (avian): Based on LC 50 (mg/kg) <50 very highly toxic; 50

- 500 highly toxic; 501

- 1000 moderately toxic;

1001

- 5000 slightly toxic; >5000 practically nontoxic

### 25

Assessment Endpoint Measures of

Effect Species Toxicity Value Endpoint Reference / Study
classification

§ Based on acute contact LD 50 (mg a.i./bee) <2 highly toxic; 2

- 10.99 moderately toxic; ≥11 practically non

- toxic

1 For honey bee studies, c lassification and endpoints based on most recent review of DER as discussed in Amended Reviews issued April 9, 2014 for MRIDs 45656813 and 45863813



### As discussed in the 2004 risk assessment and subsequent new use assessments since that time, pollinators (and non-target terrestrial invertebrates) remain an area of risk concern. Based on

reg istrant efficacy data, flonicamid’s mode of action works by causing the exposed invertebrate to stop eating. Therefore, death is caused by starvation and/or dehydration. Mortality does not
ty pically occur until 2 to 5 days after exposure. The available data on acute contact and oral
toxicit y testing for honey bees, which did elicit coordination problems, apathy, and nervousness, may not be effective in capturing the delayed toxicity produced by the chemical. In 2014, new guidan ce was issued for pollinator risk assessment, including study guidance on adult chronic
and lar val toxicity testing. Tier I and Tier II tests conducted according to the new pollinator guidan ce would help to better characterize effects of flonicamid to honey bees.

Delayed mortality concerns are also evident in the available freshwater invertebrate studies. The acute freshwater study for Daphnia was conducted as a limit test at 100 mg/L for 48 hours, where no effects were seen at the 48 hour endpoint. However, as previously discussed for

terre strial invertebrates, mortality is generally not seen until 2 to 5 days after exposure even though feeding cessation occurs more rapidly. In the 21 day freshwater invertebrate study, an

LC 50 

### of 42 mg/L was determined, which is a lower value than that determined in the acute study.
This was due to delayed mortality, with deaths in the 100 mg/L group not beginning until day 5
and de aths in the 50 mg/L group starting at day 16 and still continuing at d ay 21 . As there is a limited understanding of the mechanism of action of flonicamid and a known delayed mortality in efficacy studies, a modified acute freshwater invertebrate study using a 48 hour flow-through exposure period followed by an extended observation period in clean water flow-through would help to better characterize these effects.

Sim ilar concerns are raised with the acute estuarine/marine invertebrate 96 hour study for mysid, where delayed mortality may not be captured. Moreover, no chronic study for estuarine/marine invertebrates was submitted. A modified mysid acute study, similar to that for freshwater
inver tebrates, would help to reduce this uncertainty

.

Exposure Pathways of Concern

The exposure pathways for flonicamid and its transformation products may result in a wide range of potential a quatic and terrestrial exposure scenarios. For this problem formulation, the drinking water and inhalation pathways for birds and mammals were screened using the SIP (Screening Imbibition Program) and STIR (Screening Tool for Inhalation Risk) screening methods. STIR
found the inha lation pathway not likely to be significant but the SIP analysis identified exposure through drinking water alone to be a potential concern for birds and mammals. This is primarily
due to t he high water solubility of the compound and is a route of exposure that will be further analyzed in the forthcoming risk assessment.

### 26

It is also noted that the se screening analyses do not include aggregation with all other exposure pathways (dietary, dermal, inhalation, or drinking water), which, together, may contribute to a total exposure that has a potential for effects to non-target animals. The risk characterization section will discusses the impact of the consideration of other routes of exposure that have been identified as potentially important, and the degree of certainty associated with screening-level
risk assessment conclusions. SIP and STIR are described in detail at http:/ /www.epa.gov/oppefed1/models/terrestrial/index.htm and the SIP and STIR model outputs
are available in Appendices B and C , respectively.

4. ANALYSIS PLAN

Drinking Water Assessment

If needed, an updated drinking water assessment will be conducted to support future human
hea lth dietary risk assessments of flonicamid. The drinking water assessment will incorporate
model esti mates of flonicamid (as TTR) and any additional transformation products to those previous ly identified by the Health Effects Division as residues of toxicological concern in
surfa ce water and groundwater. The registration review drinking water assessment will include modeling re sults as well as a summary of available surface water and groundwater monitoring data, if available. The cranberry use scenario will likely be modeled using PFAM (Pesticides in
Flooded A pplication Model), which allows for a more advanced evaluation than the previously utilized Tier I rice model. This scenario represents a unique circumstance as it is a semi-aquatic

crop a nd has implications for modeling both ecological and drinking water risks.

The current model for conducting drinking water assessments for surface water is the Surface

Wa ter Concentration Calculator (SWCC), which utilizes PRZM version 5.0+ (PRZM5) and the Variable Volume Water Body Model (VVWM). The SWCC will be used to simulate pesticide
transport a s a result of runoff and erosion from an agricultural field and to estimate

e nvironmental fate and transport of pesticides in the index reservoir. Measures of exposure will be based on maximum single and year ly (including multiple seasons per year) labeled application rates, minimum retreatment intervals, and conservative methods of application.
These may also incorporate maximum use rate assumptions where maximum annual application

rates a re missing or unclear.

Currently, groundwater modeling is completed using PRZM-Groundwater (PRZM-GW version 1.0, December 11, 2012), using the GW-GUI (Graphical User Interface, version 1.0, December 11, 2012). PRZM-GW can be used to simulate vertical pesticide transport through the soil profile into an aquifer following application to an agricultural field. The PRZM scenarios used in groundwater simulations are representative of vulnerable sites

— shallow unconfined aquifers under an agricultural field with leaching prone soil

— and output values represent pesticide concentrations that may be observed in drinking water resulting from the use of groundwater
vulnera ble to pesticide contamination as source water. The results are expected to represent the upper bound values on the concentrations of toxic residues that might be found in drinking water supplied by groundwater.

### 27

Ecological Risk Assessment

Stressors of Concern

There are five degradation products of flonicamid and no toxicity data based on laboratory studies are available for these products. Known transformation kinetics and physical characteristics of these compounds are outlined in Tab les 7 and 8 and Appendix A . These products form primarily under aerobic conditions and, similar to the parent compound, degrade rapidl y under aerobic conditions. Under anaerobic conditions, the major transformation product
is TFNA , which is stable under these conditions. As the mechanism of action of the parent compound i s not well defined and the active moiety has not been identified, other tools were
used to asse ss whether the degradation products will have more or less toxicity than flonicamid
itse lf. Using ECOSar (Ecological Structure Activity Relationship), v1.11, and SMILES Codes
for each degradation product, potential toxicity of these chemicals was assessed. Output from this assessment generally indicated lower predicted toxicity for each of the degradation products than the parent and are summarized in Appendix D

.

Previous assessments have relied on the Total Toxic Residue (TTR) approach for assessing ecological and drinking water risks from flonicamid and degradates. This modeling strategy require s an assumption that all residues of concern have similar physical, chemical, and partitioning characteristics as well as equal or less toxicity than the parent compound. In the
abse nce of toxicity studies on the degradation products and based on QSAR analysis, and following the approach used in previous assessments and by HED for addressing metabolites of

conc ern, it is anticipated the TTR approach will be utilized for the risk assessment.

Measures of Exposure

In order to estimate risks of flonicamid exposure to aquatic and terrestrial organisms, all exposure modeling and resulting risk conclusions will be made based on maximum application rates, application methods, and any mitigation measures specifically indicated on the label. The models that will be used to predict the estimated environmental concentrations (EECs) of
flonicamid are discussed on OPP’s model website. 3 

### These models include: SWCC, AgDrift, AgDisp, T-REX, and TerrPlant.



## Measure of Effects

Ecological effects data are used as measures of direct and indirect effects to biological receptors. Data are typically obtained from registrant-submitted studies and from literature studies identified by ECOTOX. The ECOTOX database provides more ecological effects data in an attempt to bridge existing data gaps. ECOTOX is a source for locating single chemical toxicity data and potential chemical mixture toxicity data for aquatic life, terrestrial plants, and wildlife. ECOTOX was created and is maintained by the U.S. EPA, Office of Research and

De velopment, and the National Health and Environmental Effects Research Laboratory's MidContinent Ecology Division.

3 http://www.epa.gov/opp00001/science/models_pg.htm

### 28



## Integration of Exposure and Effects

Risk characterization is the integration of exposure and ecological effects to determine the potential ecological risk from the use of pesticides and the likelihood of direct and indirect effects to non-target organisms in aquatic and terrestrial habitats. For the assessment of risks, the risk quotient (RQ) method is used to compare exposure and measured toxicity values. EECs are

ca lculated for acute and chronic concentrations and are compared to acute and chronic toxicity endpoint s. The resulting RQs are then compared to the Agency’s Levels of Concern (LOCs) (USEPA 2004). These criteria will be used to indicate when flonicamid use, as directed on the label, ha s the potential to cause adverse direct effects to non-target organisms. In addition, any

ava ilable incident data will be considered (see below) as part of the risk characterization.



## Endangered Species Assessments

In November 2013, the EPA, along with the U.S. Fish & Wildlife Service (USFWS), the National Marine Fisheries Service (NMFS) (collectively, the Services), and the U.S. Department of Agriculture (USDA) released a summary of their joint Interim Approaches for assessing risks to listed species from pesticides. The Interim Approaches were developed jointly by the agencies

i n response to the National Academy of Sciences’ (NAS) recommendations and reflect a common approach to risk assessment shared by the agencies as a way of addressing scientific differences between the EPA and the Services. The NAS report outlines recommendations on specific scientific and technical issues related to the development of pesticide risk assessments that EPA and the Services must conduct in connection with their obligations under the Endangered Species Act (ESA) and FIFRA. The joint Interim Approaches were released prior to a stakeholder workshop held on November 15, 2013. In addition, the EPA presented the joint Interim Approaches at the December 2013 Pesticide Program Dialogue Committee (PPDC) and State-FIFRA Issues Research and Evaluation Group (SFIREG) meetings, and held a stakeholder workshop i n April 2014, allowing additional opportunities for stakeholders to comment on the Interim Approaches. As part of a phased, iterative process for developing the Interim Approaches, the agencies will also consider public comments on the Interim Approaches in

conne ction with the development of upcoming Registration Review decisions. The details of the joint Interim Approaches are contained in the white paper “Interim Approaches for National

Level Pesticide Endangered Species Act Assessments Based on the Recommendations of the
Nati onal Academy of Sciences April 2013 Report,” dated November 1, 2013.

Given that the agencies are continuing to develop and work toward implementation of the Interim Approaches to assess the potential risks of pesticides to listed species and their designated critical habitat, the ecological risk assessment supporting the proposed interim registration review decision for flonicamid is not expected to contain a complete ESA analysis. Once the agencies have fully vetted the scientific methods necessary to complete risk assessments for endangered and threatened (listed) species and their designated critical habitats, these methods will be applied to subsequent analyses for flonicamid as part of completing this

reg istration review.

### 29



## Endocrine Disruptor Screening Program

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

Review of Incident Data

Thre e incident databases are available: 1) the Ecological Incident Information System v. 2.1.1 (EIIS), maintained by EFED; 2) the Avian Incident Monitoring System (AIMS), maintained by the American Bird Conservancy; and, 3) the Incident Data System (IDS) maintained by OPP.
These databases were searched on 8/15/2014.

Two incidents are reported in the EIIS, one involving plants that was considered possibly linked to flonicamid use and another involving bees that was considered unlikely. A more detailed
desc ription of the likely incident data is provided below.

Incident #I021090-014 : A plant incident occurred on August 1, 2009 in Merced County,

C alifornia and was associated with the use of flonicamid on cotton and involved damage to 200- 300 acres of the treated cotton. Foliage samples collected from cotton sites were not submitted
for a nalysis due to the possible same day helicopter application of an undetermined pesticide.
The le gality of this application is unknown. These sites were sprayed by two different aerial Pest Control Businesses on August 1, 2009. A fixed wing aircraft with a mixture of Carbine 50 WG / FMC (a.i. flonicamid) sprayed five cotton sites, and three out of five showed symptoms of possible pesticide damage. A helicopter with the same application, sprayed three cotton sites and one out of three cotton sites showed symptoms of possible pesticide damage. Adverse effects observed include wilting and feathering of the leaves. The certainty classification for this incident was categorized as possible.

There were no incidents reported in AIMS and no aggregate incidents reported in IDS for flonicamid. The absence of documented incidents in these databases does not necessarily mean
that such incide nts did not occur. Mortality incidents must be seen, reported, investigated, and submitted to the Agency in order to be recorded in the incident databases. In addition, incident reports for non-target organisms typically provide information only on mortality events and plant damage. Sublethal effects in organisms such as abnormal behavior, reduced growth and/or impaired reproduction are rarely reported, except for phytotoxic effects in terrestrial plants.

Uncertainties

- Several of the labels identified for flonicamid uses in Table 3 do not specify the

max imum number of applications that can be applied per year and/or the number of crop

cy cles per year. We request that in completing the Use Pattern Summary Table, the registrants provide this information.

- The delayed mortality of flonicamid adds to uncertainty in the interpretation of acute toxicity results. Based on registrant efficacy studies, although feeding cessation occurs rapidly in invertebrates, mortality may be delayed until 2-5 days after exposure. Many of

### 30

the acute battery of tests only observe effects for 48
- 96 hours, which may not accurately quantify mortality rates associated with acute exposure. Moreover, due to the limited
information on the mechanism of action of the chemical, it is difficult to predict how this effect is preserved across species.

- No seedling emergence or vegetative vigor toxicity data are available to assess the potential effects of the maximum seasonal application rate (0.268 lbs a.i./A) on non-target terrestrial plants. The submitted terrestrial plant toxicity tests (MRIDs 45854917 and 45854918) we re conducted with a flonicamid treatment of 0.134 lbs a.i./A, a

conc entration that is half of the maximum application rate on the label. Although therewere no observable effects in these studies, the potential toxicity of flonicamid to nontarget plants after the proposed maximum application rate is unknown.

- Chronic data for estuarine/marine fish and invertebrates were not submitted by the registrant. The chronic measurement endpoints could not be estimated using the
freshwater fish or invertebrate acute- to -chronic NOAEC ratio because the acute endpoints were not discrete for either taxa ( i.e. freshwater fish LC 50 

### > 98 and >120 mg a.i./L; freshwater invertebrates, LC 50 

### > 99 and > 121 mg a.i./L, respectively). Consequently, the potential chronic risks to saltwater fish and invertebrates are unknown. However, under the assumption that estuarine/marine animals are not more sensitive than their freshwater counterparts, risks to estuarine/marine animals are not expected.

- Anaerobic metabolism, hydrolysis, and photolysis data were not submitted for the five

non -volatile flonicamid degradation products. Flonicamid and the five identified degra dates are all very mobile, and all degrade quickly in terrestrial aerobic environments. However, submitted metabolism data indicate that flonicamid, and the one reported anaerobic metabolism degradation product (TFNA), are expected to be persistent under anaerobic conditions. It is not possible to determine if the four remaining flonicamid degradation products are likely to persist and accumulate once they move out of aerobic environmental compartments into anaerobic ones.

### 31

5. PRELIMINARY IDENTIFICATION OF DATA GAPS

Environmental Fate

Table 11 identifies the environmental fate studies by MRID that offer data for each guideline requirement, as well as study classifications and whether or not further data are anticipated to be needed in order to support risk assessment for the flonicamid registration review.

Table 11. Submitted Environmental Fate Data for Flonicamid

OCSPP
Guideline Data

Requirement Submitted

Studies (MRID) Study

Classifications Are data

needed to
conduct risk
assessment? Additional Comments

835.2120 Hydrolysis 45656801 Acceptable No None

835.2240 Aqueous

photolysis 45656802 Acceptable No None

835.2410 Soil photolysis 45656803 Acceptable No None

835.4100 Aerobic soil

metabolism 45656804

45854817 Supplemental

Acceptable No None

835.4100 Aerobic soil

metabolism 45854819 S upplemental No Degradate TFNA

- AM

835.4100 Aerobic soil

metabolism 45854820 S upplemental No Degradate TFNG

- AM

835.4100 Aerobic soil

metabolism 45863808 S upplemental No Degradate TFNA

835.4100 Aerobic soil

metabolism 45863809 S upplemental No Degradate TFNG

835.4100 Aerobic soil

metabolism 45863810 S upplemental No Degradate TFNA

- OH

835.4200 Anaerobic soil

metabolism 45854821

46222701 Acceptable No None

835.4300 A erobic aquatic

metabolism 45854822 A cceptable No None

835.4400 Anaerobic

aquatic

metabolism 45854821

46222701 Acceptable No None

835.1230 Ad sorption/

desorption 45854902 Acceptable No None

835.1230 Ad sorption/

desorption 45854902

45854901
45854903
45854904
4585490 5 Acceptable No TFNG

TFNA

TFNA

- OH

TFNA

- AM
TFNG

- AM (MRID corresponds to study for each listed degradate)

835.1410 Volatility

–

laboratory No study No study No Not triggered based on l ow vapor pressure ( 7.07X10

- 9 torr at 25 °C)

### 32

OCSPP
Guideline Data

Requirement Submitted

Studies (MRID) Study

Classifications Are data

needed to
conduct risk
assessment? Additional Comments

835.6100 Terrestrial field

dissipation 45854906,

45854907, 45854908, 45854909,
45863811 Acceptable No None

835.6200 Aquatic field

dissipation No data No Not triggered based on exposure aquatic toxicity profile.

850.1730 Fish

bioconcentration No data No Low K ow indicates a low potential for
bioaccumulation.

850.6100 Analytical

method in soil 45854815 / 45854814 No None

850.6100 Analytical

method in w ater No data Yes Analytical method (ECM) and Independent Laboratory Validation (ILV) for water is needed

.



### Ecological Effects

Tab les 12 and 13 identify the ecological effects studies, as well as study classifications, and
whe ther or not further data are anticipated to be needed in order to support risk assessment for

reg istration review. The rationale for the additional data requested is presented below the tables.

Table 12. Submitted Aquatic Ecological Effects Data for Flonicamid

OCSPP
Guideline Data

Requirement Submitted

Studies (MRID) Study

Classifications Are data

needed to

conduct
risk
assessment? Comments

850.1010 Freshwater

invertebrate acute toxicity 45656806 Supplemental Yes Due to concern about delayed toxicity not being captured in the initial acute study, a n additional study is requested.

This is further discussed in
Section 3 and below

.
850.1025

850.1035 Saltwater

invertebrate acute toxicity 45854911 Acceptable

Yes Due to concern about delayed toxicity not being captured in the initial acute study, a n additional study is requested.

This is further discussed in
Section 3 and below

. 45854912 Supplemental

850.1075 Freshwater fish

acute toxicity 45656807 Supplemental No None

45656808 Supplemental

850.1075 Saltwater fish

acute toxicity 45854913 Supplemental No None

### 33

OCSPP
Guideline Data

Requirement Submitted

Studies (MRID) Study

Classifications Are data

needed to

conduct
risk
assessment? Comments

850.1300 Freshwater

invertebrate life cycle 45863812 Supplemental No None

850.1350 Saltwater

invertebrates life cycle No data No data No U nder the assumption that
estuarine/marine animals are not
more sensitive than their freshwater counterparts, risks to
estuarine/marine animals are not expected.

850.1735 Benthic

invertebrates (acute) No data No Not triggered per 40 CFR Part
158 based on chemical

characteristics

850.1740 Benthic

invertebrates (chronic) No data No No t triggered per 40 CFR Part
158 based on chemical

characteristics

850.1400 Freshwater fish

early

- life stage 45854914 Acceptable No None

850.1400 Saltwater fish

early

- life stage No data No U nder the assumption that
estuarine/marine animals are not
more sensitive than their freshwater counterparts, risks to
estuarine/marine animals are not expected. 850.1500 Fish life cycle

No data No

850.4400 Aquatic plant

growth:
Tier II vascular plants 45854919 Acceptable No None

850.5400 Aquatic Plant

Growth:

Tier II algae 45656814 Supplemental

No None

45854920 Acceptable

### 34

Table 13. Submitted Terrestrial Ecological Effects Data for Flonicamid

OCSPP
Guideline Data

Requirement Submitted

Studies (MRID) Study

Classifications Are data

needed for
risk
assessment? Comments

850.2100 Avian oral

toxicity 46159701 Acceptable Yes Based on new guideline requirements and available toxicity data, a passerine study is request ed No data for passerine

850.2200 Avian dietary

toxicity 45 656811 Supplemental No None

45656812 Acceptable

850.2300 Avian

reproduction 45854915 Acceptable

No None

45854916 Acceptable

Non

guideline Avian inhalation No data No None

81

- 1 Acute
mammalian o ral

LD 50 (rat) 45656707 Acceptable No None

83

- 4 Mammalian Reproduction (rat) 4 5854613 Acceptable

No None

45854612 Acceptable

850.3020 Honey bee acute

contact toxicity 45656813 Acceptable

Technical

Yes Due to concern about behavioral changes noted at low exposure levels, the delayed mortality in
invertebrates associated with this chemical and the adoption of new pollinator guidance, the Tier I and
Tier II studies outlined in the new pollinator guidance will be needed including :

Tier I: Adult, Acute Contact Adult, Acute Oral Adult, Chronic Oral Larval Acute (single dose) Larval Chronic (repeat dose)

Foliar Residue

Tier II:
Semi

- field, Tunnel
Semi

- field, Feeding

S tudy protocols will need to be evaluated and potentially modified to capture the delayed mortality

effects of flonicamid

. 45854612 Supplemental

Flonicamid 50

WG (formulated)

Non

guideline Honey bee acute

oral toxicity 45656813 Supplemental

Technical

45863813 Supplemental

Flonicamid 50

WG (formulated)

850.3030 Honey bee

residue on foliage

No data Yes

### 35

OCSPP
Guideline Data

Requirement Submitted

Studies (MRID) Study

Classifications Are data

needed for
risk
assessment? Comments

850.3040 Field testing for

pollinators No data No None

### 36

850.4100 Terrestrial plant

toxicity:

Tier I seedling

emergence 45854917 Acceptable Yes The submitted terrestrial plant toxicity tests were conducted with
a flonicamid treatment of 0.134 lbs a.i./A, a concentration that is half of the maximum application rate
on the label. Additionally, there was an incident reported for plant damage to cotton. 850.4150 Terrestrial plant

toxicity: Tier I vegetative vigor 45854918 Acceptable Yes

124

- 1 Terrestrial Plant

Field Testing No data No None

124

- 2 Aquatic Plant

Field Testing No data No None

Non

Guideline Acute Oral

Insect (50WG) (honey bee) 45863813 Supplemental Yes See discussion above on honey bee

studies

Beneficial Insect [ parasitic wasp

, ( Aphidius rhopalosiphi )]
45854921 Supplemental No None

Beneficial Insect [ green lacewing

, ( Chrysoperla

carnea )] 45854922 Supplemental No

Beneficial Insect [predatory mites

, ( Typhlodroumus pyri ) ] 45854923 Supplemental No

Beneficial Insect [carabid beetles

, ( Poeilus

cupreus ) ] 45854924 Supplemental No

Beneficial Insect [ Asian lady

beetle ( Harmonia axyridis ), predacious mite ( Phytoseiulus persimilis ) and

domestic silk

mot h ( Bombyx

mori ) ] 45863814 Supplemental No

Earthworm
Subchronic 45854925 Supplemental No

### 37

For freshwater and saltwater invertebrates, studies are recommended to address the delayed
toxicit y seen with this compound. Under OCSPP Guideline 850.1010 (freshwater) and 850.1035 (saltwater

– mysid), the test duration is only 96 hours. According to the mechanism of action of flonicamid, feeding cessation occurs rapidly but mortality does not occur until 2 to 5 days after

ex posure. For this reason, the standard protocol for acute studies does not adequately characterize mortality rates for this chemical. Extending the observation period beyond 96 hours following a cute exposure to flonicamid will be requested.

### 38 APPENDIX A

FLONICAMID AND ITS ENVIRONMENTAL DEGRADA TES

Code Name/ Synonym Chemical Name Chemical Structure Study Type MRID Maximum

Formation (% Applied)

PARENT

Flonicamid CAS Name:

N

- (cyanomethyl)

- 4

- (trifluoromethyl)

- 3

- pyridinecarboxamide

CAS Number: 158062

- 67

- 0

Molecular Weight: 229 g/mol

Chemical Formula: C 9 H 6 F 3 N 3 O

SMILES: C1=CN=CC(=C1C(F)(F)F)C(=O)NCC#N Parent structure shown for reference

TRANSFORMATION PRODUCTS

TFNG CAS Name:

N

- (4

- Trifluoromethylnicotinoyl) glycine

Molecular Weight : 248.16 g/mol

Chemical Formula: C 9 H 7 F 3 N 2 O 3

SMILES:

C 1 CNCC ( C 1C(F)(F)F)C(=O)NCC(=O)O photolysis in soil 45656803 2.0%*

aerobic soil metabolism 45854818 3.9%

aerobic aquatic metabolism 45854822 3.7%

### 39

Code Name/ Synonym Chemical Name Chemical Structure Study Type MRID Maximum

Formation (% Applied)

TFNA CAS Name:

4

- Trifluoromethylnicotinic acid

Chemical Formula: C 7 H 4 F 3 NO 2

Molecular Weight: 191.11

SMILES: C1=CN=CC(=C1C(F)(F)F)C(=O)O aerobic soil metabolism 45656804 36%

aerobic aquatic metabolism 45854822 18%

anaerobic aquatic

metabolism 45854821 76%*

TFNA

- OH CAS Name:

6

- Hydroxy

- 4

- trifluoromethylnicotinic

acid

Chemical Formula: C 7 H 4 F 3 NO 3

Molecular Weight: 207.11

SMILES: C1=C(C(=CN=C1O)C(=O)O)C(F)(F)F aerobic soil metabolism 45656804 21%

aerobic aquatic metabolism 45854822 7.6%

TFNA

- AM CAS Name:

4

- Trifluoromethylnicotinamide

Chemical Formula: C 7 H 5 F 3 N 2 O

Molecular Weight: 190.13

SMILES: C1=CN=CC(=C1C(F)(F)F)C(=O)N hydrolysis 45656801 3.4%

photolysis in water 45656802 3.0%

photolysis in soil 45656803 5.0%*

aerobic soil metabolism 45854818 7.6%

aerobic aquatic metabolism 45854822 1.4%

TFNG

- AM CAS Name:

N

- (4

- Trifluoromethylnicotinoyl) glycinamide

Chemical Formula: C 9 H 8 F 3 N 3 O 2

Molecular Weight: 247.18 photolysis in soil 45656803 16%

aerobic soil metabolism 45854818 10%

### 40

Code Name/ Synonym Chemical Name Chemical Structure Study Type MRID Maximum

Formation (% Applied)

SMILES: C1=CN=CC(=C1C(F)(F)F)C(=O)NCC(= O)N

“*” Indicates maximum % of applied reported at study termination; amount may have continued to increase with time

Bold denotes major degradate

### 41 APPENDIX B
SIP ANALYSIS

Table 1. Inputs

Parameter Value

Chemical name Flonicamid
Solubility (in water at 25 o C; mg/L) 5300

Mammalian LD 50 (mg/kg

- bw) 884 Mammalian test species laboratory rat Body weight (g) of "other" mammalian species

Mammalian NOAEL (mg/kg

- bw) 90 Mammalian test species laboratory rat Body weight (g) of "other" mammalian species

Avian LD 50 (mg/kg

- bw) 2250 Avian test species northern bobwhite quail Body weight (g) of "other" avian species Mineau scaling factor 1.15

Mallard NOAEC (mg/kg

- diet) 5037 Bobwhite quail NOAEC (mg/kg

- diet) 4617 NOAEC (mg/kg

- diet) for other bird species Body weight (g) of other avian species NOAEC (mg/kg

- diet) for 2nd other bird species Body weight (g) of 2nd other avian species

Table 2. Mammalian Results

Parameter Acute Chronic Upper bound exposure (mg/kg

- bw) 911.6000 911.6000 Adjusted toxicity value (mg/kg

- bw) 679.9379 69.2245 Ratio of exposure to toxicity 1.3407 13.1688

Conclusion* Exposure through drinking water alone is a potential concern for
mammals Exposure through

drinking water alone is a potential concern for
mammals

### 42

Table 3. Avian Results

Parameter Acute Chronic Upper bound exposure (mg/kg

- bw) 4293.0000 4293.0000 Adjusted toxicity value (mg/kg

- bw) 1620.9664 249.8985 Ratio of exposure to acute toxicity 2.6484 17.1790

Conclusion* Exposure through drinking water alone is a potential concern for
birds Exposure through

drinking water alone is a potential concern for
birds

*Conclusion is for drinking water exposure alone. This does not combine all routes of exposure. Therefore, when aggregated with other routes ( i.e ., diet, inhalation, dermal), pesticide exposure through drinking water may contribute to a total exposure that has potential fo r effects to non

- target animals.

### 43 APPENDIX C
STIR ANALYSIS



# Welcome to the EFED Screening Tool for Inhalation Risk

This tool is designed to provide the risk assessor with a rapid method for determining the potential significance of the inhalation exposure route to birds and mammals in a risk assessment.



# Input

Application and Chemical Information

Enter Chemical Name Flonicamid

Enter Chemical Use Foliar Is the Application a Spray? (enter y or n) y If Spray What Type (enter ground or air) ground Enter Chemical Molecular Weight (g/mole) 229 Enter Chemical Vapor Pressure (mmHg) 7.07E

- 09 Enter Application Rate (lb a.i./acre) 0.287

Toxicity Properties

Bird

Enter Lowest Bird Oral LD 50 (mg/kg bw) 2250 Enter Mineau Scaling Factor 1.15 Enter Tested Bird Weight (kg) 0.178

Mammal

Enter Lowest Rat Oral LD 50 (mg/kg bw) 884

Enter Lowest Rat Inhalation LC 50 (mg/L) 5.36 Duration of Rat Inhalation Study (hrs) 4

Enter Rat Weight (kg) 0.35



# Output

Results Avian (0.020 kg ) Maximum Vapor Concentration in Air at Saturation (mg/m 3 ) 8.71E

- 05

Maximum 1

- hour Vapor Inhalation Dose (mg/kg) 1.10E

- 05

Adjusted Inhalation LD 50 7.61E+01

Ratio of Vapor Dose to Adjusted Inhalation LD 50 1.44E

- 07 Exposure not Likely Significant

Maximum Post

- treatment Spray Inhalation Dose (mg/kg) 3.03E

- 02 Ratio of Droplet Inhalation Dose to Adjusted Inhalation
LD 50 3.99E

- 04 Exposure not Likely Significant

### 44

Results Mammalian (0.015 kg ) Maximum Vapor Concentration in Air at Saturation (mg/m 3 ) 8.71E

- 05

Maximum 1

- hour Vapor Inhalation Dose (mg/kg) 1.38E

- 05

Adjusted Inhalation LD 50 3.19E+02

Ratio of Vapor Dose to Adjusted Inhalation LD 50 4.31E

- 08 Exposure not Likely Significant

Maximum Post

- treatment Spray Inhalation Dose (mg/kg) 3.81E

- 02 Ratio of Droplet Inhalation Dose to Adjusted Inhalation
LD 50 1.19E

- 04 Exposure not Likely Significant

### 45

APPENDIX D. ECOSar OUTPUT RESULTS

Flonicamid:

ECOSAR Version 1.11 Results Page

SMILES : c1cncc(c1C(F)(F)F)C(=O)NCC(#N)

CHEM :

CAS Num:

ChemID1:

MOL FOR: C9 H6 F3 N3 O1

MOL WT : 229.16 Log Kow: 0.502 (EPISuite Kowwin v1.68 Estimate) Log Kow: (User Entered) Log Kow: (PhysProp DB exp value - for comparison only) Melt Pt: (User Entered for Wat Sol estimate) Melt Pt: (deg C, PhysProp DB exp value for Wat Sol estimate) Wat Sol: 6222 (mg/L, EPISuite WSKowwin v1.43 Estimate)
Wat Sol: (User Entered) Wat Sol: (PhysProp DB exp value)

-------------------------------------- Values used to Generate ECOSAR Profile

-------------------------------------- Log Kow: 0.502 (EPISuite Kowwin v1.68 Estimate) Wat Sol: 6222 (mg/L, EPISuite WSKowwin v1.43 Estimate)

-------------------------------------- ECOSAR v1.11 Class-specific Estimations

-------------------------------------- Amides

Predicted

E COSAR Class Organism Duration End Pt mg/L (ppm)

### 46

=========================== ================== ======== ====== ========== Amides : Fish 96-hr LC50 806.344

Amides : Daphnid 48-hr LC50 1770.232 Amides : Green Algae 96-hr EC50 18.356

Amides : Fish ChV 0.567 Amides : Daphnid ChV 36.941 Amides : Green Algae ChV 9.166 Amides : Fish (SW) 96-hr LC50 701.504 Amides : Mysid (SW) 96-hr LC50 27.659

=========================== ================== ======== ====== ========== Neutral Organic SAR : Fish 96-hr LC50 4167.906 (Baseline Toxicity) : Daphnid 48-hr LC50 2060.896 : Green Algae 96-hr EC50 866.604

: Fish ChV 346.076 : Daphnid ChV 136.773 : Green Algae ChV 166.789

Note: * = asterisk designates: Chemical may not be soluble enough to measure this predicted effect. If the effect level exceeds the water solubility by 10X, typically no effects at saturation (NES) are reported.

------------------------------ Class Specific LogKow Cut-Offs

------------------------------ If the log Kow of the chemical is greater than the endpoint specific cut -offs presented below, then no effects at saturation are expected for those endpoints.

Amides :

------- Maximum LogKow: >8.5 (LC50) Maximum LogKow: >8.0 (EC50,ChV)

### 47

Baseline Toxicity SAR Limitations:

--------------------------------- Maximum LogKow: 5.0 (Fish 96-hr LC50; Daphnid LC50) Maximum LogKow: 6.4 (Green Algae EC50) Maximum LogKow: 8.0 (ChV)

TFNA- OH :

ECOSAR Version 1.11 Results Page

SMILES : c1c(c(cnc1O)C(=O)O)C(F)(F)F

CHEM :

CAS Num:

ChemID1:

MOL FOR: C7 H4 F3 N1 O3

MOL WT : 207.11 Log Kow: 1.576 (EPISuite Kowwin v1.68 Estimate) Log Kow: (User Entered) Log Kow: (PhysProp DB exp value - for comparison only)
Melt Pt: (User Entered for Wat Sol estimate) Melt Pt: (deg C, PhysProp DB exp value for Wat Sol estimate) Wat Sol: 1813 (mg/L, EPISuite WSKowwin v1.43 Estimate)
Wat Sol: (User Entered) Wat Sol: (PhysProp DB exp value)

-------------------------------------- Values used to Generate ECOSAR Profile

-------------------------------------- Log Kow: 1.576 (EPISuite Kowwin v1.68 Estimate) Wat Sol: 1813 (mg/L, EPISuite WSKowwin v1.43 Estimate)

-------------------------------------- ECOSAR v1.11 Class-specific Estimations

### 48

-------------------------------------- Phenols-acid

Predicted ECOSAR Class Organism Duration End Pt mg/L (ppm)

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

-- > Acid moeity found: Predicted values multiplied by 10

Phenols-acid : Fish 96-hr LC50 755.320 Phenols-acid : Daphnid 48 -hr LC50 188.308 Phenols-acid : Green Algae 96 -hr EC50 902.511

Phenols-acid : Fish ChV 71.660

Phenols -acid : Daphnid ChV 35.848 Phenols-acid : Green Algae ChV 426.269 Phenols-acid : Fish (SW) 9 6-hr LC50 367.820

Phenols-acid : Earthworm 14 -day LC50 2867.428 * Phenols-acid : Lemna gibba 7 -day EC50 600.069

=========================== ================== ======== ====== ========== Neutral Organic SAR : Fish 96-hr LC50 408.710 (Baseline Toxicity) : Daphnid 48-hr LC50 223.162 : Green Algae 96 -hr EC50 141.402

: Fish ChV 38.148 : Daphnid ChV 19.518 : Green Algae ChV 33.940

Note: * = asterisk designates: Chemical may not be soluble enough to measure this predicted effect. If the effect level exceeds the water solubility by 10X, typically no effects at saturation (NES) are reported.

------------------------------ Class Specific LogKow Cut-Offs

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

### 49

If the log Kow of the chemical is greater than the endpoint specific cut-offs presented below, then no effects at saturation are expected for those endpoints.

Phenols:

------- Maximum LogKow: 7.0 (Fish 96-hr LC50, Daphnid LC50) Maximum LogKow: 6.4 (Earthworm, Lemna) Maximum LogKow: 7.0 (Green Algae EC50 Maximum LogKow: 8.0 (ChV) Maximum LogKow: 5.0 (Fish (SW) 96-hr LC50, Mysid)

Baseline Toxicity SAR Limitations:

--------------------------------- Maximum LogKow: 5.0 (Fish 96-hr LC50; Daphnid LC50) Maximum LogKow: 6.4 (Green Algae EC50) Maximum LogKow: 8.0 (ChV)

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

TFNA:

ECOSAR Version 1.11 Results Page

SMILES : c1cncc(c1C(F)(F)F)C(=O)O

CHEM :

CAS Num:

ChemID1:

MOL FOR: C7 H4 F3 N1 O2

MOL WT : 191.11 Log Kow: 1.306 (EPISuite Kowwin v1.68 Estimate) Log Kow: (User Entered) Log Kow: (PhysProp DB exp value - for comparison only)
Melt Pt: (User Entered for Wat Sol estimate)

### 50

Melt Pt: (deg C, PhysProp DB exp value for Wat Sol estimate) Wat Sol: 3718 (mg/L, EPISuite WSKowwin v1.43 Estimate)
Wat Sol: (User Entered) Wat Sol: (PhysProp DB exp value)

-------------------------------------- Values used to Generate ECOSAR Profile

-------------------------------------- Log Kow: 1.306 (EPISuite Kowwin v1.68 Estimate) Wat Sol: 3718 (mg/L, EPISuite WSKowwin v1.43 Estimate)

-------------------------------------- ECOSAR v1.11 Class-specific Estimations

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

****************************************************************************** | Not Related to an Existing ECOSAR Class Definition |
| | | Estimates provided below use the Neutral Organics QSAR equations which | | represent baseline toxicity potential (minimum toxicity) assuming a simple | | non-polar narcosis model. Without empirical data on structurally similar | | chemicals, it is uncertain if this substance will present significantly | | higher toxicity above baseline estimates. |

******************************************************************************

Predicted ECOSAR Class Organism Duration End Pt mg/L (ppm)

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

-- > Acid moeity found: Predicted values multiplied by 10

Neutral Organics-acid : Fish 96-hr LC50 6588.804 *

### 51

Neutral Organics-acid : Daphnid 48-hr LC50 3509.079 Neutral Organics -acid : Green Algae 96-hr EC50 2005.831 Neutral Organics-acid : Fish ChV 597.172 Neutral Organics-acid : Daphnid ChV 286.344 Neutral Organics-acid : Green Algae ChV 455.466 Neutral Organics -acid : Fish (SW) 96-hr LC50 8260.440 * Neutral Organics-acid : Mysid 96 -hr LC50 9821.104 * Neutral Organics-acid : Fish (SW) ChV 587.030 Neutral Organics-acid : Mysid (SW) ChV 1042.621 Neutral Organics-acid : Earthworm 14 -day LC50 3921.125 *

Note: * = asterisk designates: Chemical may not be soluble enough to measure this predicted effect. If the effect level exceeds the water solubility by 10X, typically no effects at saturation (NES) are reported.

------------------------------ Class Specific LogKow Cut-Offs

------------------------------ If the log Kow of the chemical is greater than the endpoint specific cut -offs presented below, then no effects at saturation are expected for those endpoints.

Neutral Organics:

---------------- Maximum LogKow: 5.0 (Fish 96-hr LC50; Daphnid LC50, Mysid LC50) Maximum LogKow: 6.0 (Earthworm LC50) Maximum LogKow: 6.4 (Green Algae EC50) Maximum LogKow: 8.0 (ChV)

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

### 52

ECOSAR Version 1.11 Results Page

SMILES : c1cncc(c1C(F)(F)F)C(=O)O

CHEM : TFNA

CAS Num:

ChemID1:

MOL FOR: C7 H4 F3 N1 O2

MOL WT : 191.11 Log Kow: 1.306 (EPISuite Kowwin v1.68 Estimate) Log Kow: (User Entered) Log Kow: (PhysProp DB exp value - for comparison only) Melt Pt: (User Entered for Wat Sol estimate) Melt Pt: (deg C, PhysProp DB exp value for Wat Sol estimate) Wat Sol: 3718 (mg/L, EPISuite WSKowwin v1.43 Estimate)
Wat Sol: (User Entered) Wat Sol: (PhysProp DB exp value)

-------------------------------------- Values used to Generate ECOSAR Profile

-------------------------------------- Log Kow: 1.306 (EPISuite Kowwin v1.68 Estimate) Wat Sol: 3718 (mg/L, EPISuite WSKowwin v1.43 Estimate)

-------------------------------------- ECOSAR v1.11 Class-specific Estimations

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

****************************************************************************** | Not Related to an Existing ECOSAR Class Definition |
| |

### 53

| Estimates provided below use the Neutral Organics QSAR equations which | | represent baseline toxicity potential (minimum toxicity) assuming a simple | | non-polar narcosis model. Without empirical data on structurally similar | | chemicals, it is uncertain if this substance will present significantly | | higher toxicity above baseline estimates. |

******************************************************************************

Predicted ECOSAR Class Organism Duration End Pt mg/L (ppm)

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

-- > Acid moeity found: Predicted values multiplied by 10

Neutral Organics-acid : Fish 96-hr LC50 6588.804 * Neutral Organics-acid : Daphnid 48-hr LC50 3509.079 Neutral Organics-acid : Green Algae 96 -hr EC50 2005.831 Neutral Organics-acid : Fish ChV 597.172 Neutral Organics-acid : Daphnid ChV 286.344 Neutral Organics-acid : Green Algae ChV 455.466 Neutral Organics-acid : Fish (SW) 96 -hr LC50 8260.440 * Neutral Organics-acid : Mysid 96-hr LC50 9821.104 * Neutral Organics-acid : Fish (SW) ChV 587.030 Neutral Organics-acid : Mysid (SW) ChV 1042.621 Neutral Organics-acid : Earthworm 14-day LC50 3921.125 *

Note: * = asterisk designates: Chemical may not be soluble enough to measure this predicted effect. If the effect level exceeds the water solubility by 10X, typically no effects at saturation (NES) are reported.

------------------------------ Class Specific LogKow Cut-Offs

------------------------------ If the log Kow of the chemical is greater than the endpoint specific cut -offs

### 54

presented below, then no effects at saturation are expected for those endpoints.

Neutral Organics:

---------------- Maximum LogKow: 5.0 (Fish 96-hr LC50; Daphnid LC50, Mysid LC50) Maximum LogKow: 6.0 (Earthworm LC50) Maximum LogKow: 6.4 (Green Algae EC50) Maximum LogKow: 8.0 (ChV)

TFNG: ECOSAR Version 1.11 Results Page

SMILES : c1cncc(c1C(F)(F)F)C(=O)NCC(=O)O

CHEM :

CAS Num:

ChemID1:

MOL FOR: C9 H7 F3 N2 O3

MOL WT : 248.16 Log Kow: 0.233 (EPISuite Kowwin v1.68 Estimate) Log Kow: (User Entered) Log Kow: (PhysProp DB exp value - for comparison only) Melt Pt: (User Entered for Wat Sol estimate) Melt Pt: (deg C, PhysProp DB exp value for Wat Sol estimate) Wat Sol: 1.532E+004 (mg/L, EPISuite WSKowwin v1.43 Estimate)
Wat Sol: (User Entered) Wat Sol: (PhysProp DB exp value)

-------------------------------------- Values used to Generate ECOSAR Profile

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

### 55

Log Kow: 0.233 (EPISuite Kowwin v1.68 Estimate) Wat Sol: 1.532E+004 (mg/L, EPISuite WSKowwin v1.43 Estimate)

-------------------------------------- ECOSAR v1.11 Class-specific Estimations

-------------------------------------- Amides -acid

Predicted ECOSAR Class Organism Duration End Pt mg/L (ppm)

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

-- > Acid moeity found: Predicted values multiplied by 10

Amides -acid : Fish 96-hr LC50 13606.964

Amides -acid : Daphnid 48-hr LC50 33820.336 * Amides -acid : Green Algae 96 -hr EC50 292.263

Amides -acid : Fish ChV 8.158 Amides -acid : Daphnid ChV 590.774

Amides -acid : Green Algae ChV 130.264 Amides -acid : Fish (SW) 96 -hr LC50 11805.532 Amides -acid : Mysid (SW) 96-hr LC50 427.542

=========================== ================== ======== ====== ========== Neutral Organic SAR : Fish 96 -hr LC50 7878.778 (Baseline Toxicity) : Daphnid 48-hr LC50 3800.092 : Green Algae 96-hr EC50 1441.758

: Fish ChV 635.287 : Daphnid ChV 235.329 : Green Algae ChV 262.531

Note: * = asterisk designates: Chemical may not be soluble enough to measure this predicted effect. If the effect level exceeds the water solubility by 10X, typically no effects at saturation (NES) are reported.

### 56

------------------------------ Class Specific LogKow Cut-Offs

------------------------------ If the log Kow of the chemical is greater than the endpoint specific cut -offs presented below, then no effects at saturation are expected for those endpoints.

Amides :

------- Maximum LogKow: >8.5 (LC50) Maximum LogKow: >8.0 (EC50,ChV)

Baseline Toxicity SAR Limitations:

--------------------------------- Maximum LogKow: 5.0 (Fish 96-hr LC50; Daphnid LC50) Maximum LogKow: 6.4 (Green Algae EC50) Maximum LogKow: 8.0 (ChV)

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

TFNA- AM :

ECOSAR Version 1.11 Results Page

SMILES : c1cncc(c1C(F)(F)F)C(=O)N

CHEM :

CAS Num:

ChemID1:

MOL FOR: C7 H5 F3 N2 O1

MOL WT : 190.13
Log Kow: -0.223 (EPISuite Kowwin v1.68 Estimate) Log Kow: (User Entered) Log Kow: (PhysProp DB exp value - for comparison only) Melt Pt: (User Entered for Wat Sol estimate)

### 57

Melt Pt: (deg C, PhysProp DB exp value for Wat Sol estimate) Wat Sol: 3724 (mg/L, EPISuite WSKowwin v1.43 Estimate)
Wat Sol: (User Entered) Wat Sol: (PhysProp DB exp value)

-------------------------------------- Values used to Generate ECOSAR Profile

-------------------------------------- Log Kow: -0.223 (EPISuite Kowwin v1.68 Estimate) Wat Sol: 3724 (mg/L, EPISuite WSKowwin v1.43 Estimate)

-------------------------------------- ECOSAR v1.11 Class-specific Estimations

-------------------------------------- Amides

Predicted ECOSAR Class Organism Duration End Pt mg/L (ppm)

=========================== ================== ======== ====== ========== Amides : Fish 96-hr LC50 2206.592 Amides : Daphnid 48-hr LC50 6764.946 * Amides : Green Algae 96-hr EC50 42.960

Amides : Fish ChV 1.009 Amides : Daphnid ChV 87.487 Amides : Green Algae ChV 15.801 Amides : Fish (SW) 96-hr LC50 1905.648 Amides : Mysid (SW) 96-hr LC50 59.779

=========================== ================== ======== ====== ========== Neutral Organic SAR : Fish 96-hr LC50 15479.536 * (Baseline Toxicity) : Daphnid 48-hr LC50 7158.657 * : Green Algae 96 -hr EC50 2282.572

: Fish ChV 1187.761 : Daphnid ChV 394.357 : Green Algae ChV 378.483

### 58

Note: * = asterisk designates: Chemical may not be soluble enough to measure this predicted effect. If the effect level exceeds the water solubility by 10X, typically no effects at saturation (NES) are reported.

------------------------------ Class Specific LogKow Cut-Offs

------------------------------ If the log Kow of the chemical is greater than the endpoint specific cut-offs presented below, then no effects at saturation are expected for those endpoints.

Amides :

------- Maximum LogKow: >8.5 (LC50) Maximum LogKow: >8.0 (EC50,ChV)

Baseline Toxicity SAR Limitations:

--------------------------------- Maximum LogKow: 5.0 (Fish 96 -hr LC50; Daphnid LC50) Maximum LogKow: 6.4 (Green Algae EC50) Maximum LogKow: 8.0 (ChV)

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

TFNG-AM: ECOSAR Version 1.11 Results Page

SMILES : c1cncc(c1C(F)(F)F)C(=O)NCC(=O)N

CHEM :

CAS Num:

ChemID1:

### 59

MOL FOR: C9 H8 F3 N3 O2

MOL WT : 247.18 Log Kow: -1.016 (EPISuite Kowwin v1.68 Estimate) Log Kow: (User Entered)
Log Kow: (PhysProp DB exp value - for comparison only) Melt Pt: (User Entered for Wat Sol estimate) Melt Pt: (deg C, PhysProp DB exp value for Wat Sol estimate) Wat Sol: 8857 (mg/L, EPISuite WSKowwin v1.43 Estimate)
Wat Sol: (User Entered) Wat Sol: (PhysProp DB exp value)

-------------------------------------- Values used to Generate ECOSAR Profile

-------------------------------------- Log Kow: -1.016 (EPISuite Kowwin v1.68 Estimate) Wat Sol: 8857 (mg/L, EPISuite WSKowwin v1.43 Estimate)

-------------------------------------- ECOSAR v1.11 Class-specific Estimations

-------------------------------------- Amides

Predicted ECOSAR Class Organism Duration End Pt mg/L (ppm)

=========================== ================== ======== ====== ========== Amides : Fish 96-hr LC50 10595.536 *

Amides : Daphnid 48-hr LC50 46821.414 * Amides : Green Algae 96-hr EC50 173.826

Amides : Fish ChV 3.023 Amides : Daphnid ChV 358.615 Amides : Green Algae ChV 45.747 Amides : Fish (SW) 96-hr LC50 9077.204 * Amides : Mysid (SW) 96-hr LC50 221.690

### 60

=========================== ================== ======== ====== ========== Neutral Organic SAR : Fish 96-hr LC50 1.04e+005 * (Baseline Toxicity) : Daphnid 48-hr LC50 44629.660 * : Green Algae 96-hr EC50 10511.247 *

: Fish ChV 7308.154 : Daphnid ChV 2005.058 : Green Algae ChV 1480.528

Note: * = asterisk designates: Chemical may not be soluble enough to measure this predicted effect. If the effect level exceeds the water solubility by 10X, typically no effects at saturation (NES) are reported.

------------------------------ Class Specific LogKow Cut-Offs

------------------------------ If the log Kow of the chemical is greater than the endpoint specific cut -offs presented below, then no effects at saturation are expected for those endpoints.

Amides :

------- Maximum LogKow: >8.5 (LC50) Maximum LogKow: >8.0 (EC50,ChV)

Baseline Toxicity SAR Limitations:

--------------------------------- Maximum LogKow: 5.0 (Fish 96-hr LC50; Daphnid LC50) Maximum LogKow: 6.4 (Green Algae EC50) Maximum LogKow: 8.0 (ChV)

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