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

OFFICE OF CHEMICAL SAFETY AND
POLLUTION PREVENTION



# Environmental Fate and Ecological Risk Assessment
for Sulfoxaflor Registration

Sulfoxaflor: A 50 :50 Mixture of Diastereomer 1 and 2

Prepared by: Keith G. Sappington . M.S. Mohammed A. Ruhman, Ph.D.

Reviewed by: Mah Shamim, Ph.D. United States Environmental Protection Agency
Office of Pesticide Programs
Environmental Fate and Effects Division
Environmental Risk Branch V 1200 Pennsylvania Ave.
Mail Code 7507P Washington, D.C. 2046 0ii 

### Table of Contents

1. Executive Summary

................................ ................................ ................................ .............. 8

1.1. Nature of Chemical Stressor

................................ ................................ ................................ 8
1.2 Potential Risk s to Non

- target Organisms

................................ ................................ .......... 9
1.3 Conclusions

- Exposure Characterization

................................ ................................ ........ 10
1.4 Conclusions

- Effects Characterization

................................ ................................ ........... 10
1.5 Data Gaps and Uncertainties

................................ ................................ ........................... 12
1.5.1 Environmental Fate

................................ ................................ ................................ ... 12
1.5.2 Ecological Effects

................................ ................................ ................................ ..... 12
2. Problem Formulation

................................ ................................ ................................ .......... 13

2.1 Nature of the R egulatory action

................................ ................................ ....................... 13
2.2 Nature of the Chemical Stressor

................................ ................................ ..................... 13
2.2.1 Overview of Pesticide Usage

................................ ................................ .................... 13
2.2.2 Pesticide Type, Class, and Mode of Action

................................ .............................. 14
2.2.3 Overview of Physicochemical, Fate, and Transport Properties

................................ 14
2.2.4 Stressor Source, Intensity and Identity

................................ ................................ ..... 15
2.3 Ecological Receptors

................................ ................................ ................................ ....... 18
2.4 Ecosystems at Risk

................................ ................................ ................................ ......... 19
2.5 Assessment Endpoints

................................ ................................ ................................ ..... 19
2.6 Conceptual Model

................................ ................................ ................................ ............ 19
2.6.1 Diagram

................................ ................................ ................................ ..................... 20
2.6.2 Risk Hypothesis

................................ ................................ ................................ ........ 23
2.7 Analysis Plan

................................ ................................ ................................ ................... 24
2.7.1 Methods for Conducting Ecological Risk Assessment

................................ ............. 24
2.7.2 Measures of Exposure

................................ ................................ ............................... 25
2.7.3 Measures of Effect

................................ ................................ ................................ .... 26
3. Analysis

................................ ................................ ................................ ............................... 29

3.1 Use Characterization

................................ ................................ ................................ ........ 29
3.2 Exposure Characterization

................................ ................................ ............................... 30
3.2.1 Environmental Fate and Transport Characterization

................................ ................ 30

3.2.1.1 Physical and chemical properties

................................ ................................ ...... 30
3.2.1.2 Fate and Transport Properties

................................ ................................ ........... 31
3.2.2. Measures of Aquatic Exposure

................................ ................................ ................. 47
3.2.3 Terrestrial Exposure Assessment

................................ ................................ .............. 59

3.2.3.1

. Terrestrial Vertebrate Exposure Modeling

................................ ....................... 60
3.2.3.2. Terrestrial Exposure Monitoring (Field Data)

................................ .................. 61
3.2.3.3. Non

- Target Plant Exposure Assessment

................................ ........................... 61
4. Ecological Effects Characterization

................................ ................................ .................... 62

4.1 Aquatic Effects

................................ ................................ ................................ ................ 62
4.1.1 Acute Toxicity to Fish

................................ ................................ .............................. 63
4.1.2 Chronic Toxicity to Fish

................................ ................................ ........................... 64
4.1.3 Acute Toxicity to Aquatic Invertebrates

................................ ................................ ... 64
4.1.4 Chronic Toxicity to Aquatic Invertebrates

................................ ............................... 64
4.1.5 Toxicity to Aquatic Plants

................................ ................................ ........................ 66iii 4.2 Terrestrial Effects

................................ ................................ ................................ ............ 66
4.2.1 Toxicity to Birds

................................ ................................ ................................ ....... 68
4.2.2 Toxicity to Mammals

................................ ................................ ................................ 68
4.2.3 Toxicity to Bees

................................ ................................ ................................ ........ 70
4.2.4 Toxicity to Terrestria l Plants

................................ ................................ .................... 70
5. Risk Characterization

................................ ................................ ................................ .......... 71

5.1 Risk Estimation

- Integration of Exposure and Effects Data

................................ ........... 71
5.1.1. Risks to Non

- Target Aquatic Animals

................................ ................................ ...... 72

5.1.1.1. Fish and Invertebrates: Water Column Exposure

................................ ............. 73
5.1.1.2. Aquatic Invertebrates: Sediment Exposure

................................ ....................... 74
5.1.2 Risks to Aquatic Plants

................................ ................................ ............................. 76
5.1.3 Risks to Terrestrial Animals

................................ ................................ ..................... 76

5.1.3.1. Acute Risk to Mammals

................................ ................................ .................... 77
5.1.3.2. Chronic Risks to Mammals

................................ ................................ ............... 77
5.1.3.3. Acute Ri sk to Birds

................................ ................................ .......................... 79
5.1.3.4. Non

- target Terrestrial and Semi

- Aquatic Plants

................................ ............... 81
5.1.3.5. Risk Estimation for Bees

................................ ................................ ................. 81
5.2 Risk Description

- Interpretation of Direct Effects

................................ ......................... 89
5.2.1 Risks to Aquatic Animals

................................ ................................ ......................... 89
5.2.2 Risks to Aquatic Plants

................................ ................................ ............................. 89
5.2.3 Risks to Terrestrial Organisms

................................ ................................ .................. 90

5.2.3.1. Acute and Chronic Risk to Birds and Mammals

................................ .............. 90
5.2.3.2. Risks to Terrestrial Plants

................................ ................................ ................. 91
5.2.3.3. Risks to Bees

................................ ................................ ................................ ..... 91
5.2.4 Review of Incident Data

................................ ................................ ......................... 105
5.2.5 Endocrine Effects

................................ ................................ ................................ .... 105
5.2.6 Threatened and Endangered Species Concerns

................................ ...................... 105
5 .2.7 Description of Assumptions, Limitations, Uncertainties and Data Gaps

............... 107

5.2.7.1 Exposure for All Taxa

................................ ................................ ..................... 107
5.2.7.2 Exposure for Aquatic Species

................................ ................................ ......... 107
5.2.7.3 Exposure for Terrestrial Species

................................ ................................ ..... 108
5.2.7.4 Ef fects Assessment for All Taxa

................................ ................................ ..... 110
6. Literature Cited

................................ ................................ ................................ ................. 111

6.1 Environmental Fate Studies Submitted to EPA

................................ ............................. 111
6.2 Ecological Effe cts Studies Submitted to EPA

................................ ............................... 114
6.2.1 Aquatic Ecotoxicity Studies

................................ ................................ .................... 114
6.2.2 Avian Ecotoxicity Studies

................................ ................................ ....................... 116
6.2.3 Beneficial Insect Ecotoxicity Studies

................................ ................................ ..... 117
6.3 Open Literature and Government Reports

................................ ................................ ..... 119iv Table of Figures

Figure 1. Results from cotton plant translocation study with sulfoxaflor applied to leaf (Panel A&B) and stem (Panel C&D); MRID 48445804

................................ ................................ ......... 15 Figu re 2. Diagram summarizing distribution of expected residues of interest constituents in surface water and ground water.

................................ ................................ ................................ ... 16 Figure 3. An ecological conceptual model for aquatic exposure from spray application of
sulfoxaflor

................................ ................................ ................................ ................................ ..... 21 Figure 4. An ecological conceptual model for terrestrial exposure from spray application of
sulfoxaflor

................................ ................................ ................................ ................................ ..... 22 Figure 5. An ecological conceptual model for honey bee exposure from spray application of
sulfoxaflor

................................ ................................ ................................ ................................ ..... 23 Figure 6. Radiolabeled sulfoxaflor used in fate and transport studies

................................ .......... 31 Figure 7. Expected environmental degradation pathways and transformation profiles for
Sulfoxaflor

................................ ................................ ................................ ................................ .... 36 Figure 8. Distribution of sulfoxaflor residues in tomato following foliar and soil applications

.. 43 Figure 9. Distribution of maximums of sulfoxaflor residues in four crops following foliar and soil applications

................................ ................................ ................................ ............................ 45 Figure 10. Surface water peak/21

- day/60

- day for th e residues of interest EECs (μg/L) from
cotton and others

................................ ................................ ................................ ........................... 52 Figure 11. Impact of application efficiency on determined EECS for Surface Water

................. 56 Figure 12. Impact of pesticide degradation on determined EECs in the rice paddy following one (blue line), two (red line) and three (green line) application

................................ ........................ 57 Figure 13. Expected dow nstream movement, from site of application of sulfoxaflor, in flowing water in one Day

................................ ................................ ................................ ........................... 58 Figure 14. Summary of foliar dissipation half life (DT50) values for sulfoxaflor

....................... 61 Figure 15. Proposed Tiered Approach for Assessing Risk to Honey Bees from Foliar Spray Applications

................................ ................................ ................................ ................................ .. 83 Figure 16. Ratio of sulfoxaflor concentration in cot ton nectar to residue associated with the proposed acute LOC of 0.4

................................ ................................ ................................ ........... 88 Figure 17. Sulfoxaflor residues in cotton plant pollen (A), forager

- collected pollen (B) and forager collected nectar (C). Forager

- collected pollen and nectar residues are a mean from bees at two hives in each tunnel (MRID 48755606).

................................ ................................ ............ 93 Figure 18. Mean sulfoxaflor residues in plant

- collected cotton pollen over different application intervals (MRID 4875 5606)

................................ ................................ ................................ .......... 95v 

### Table of Tables

Table 1. Summary of Ecological Risk Conclusions for the Proposed Sulfoxaflor Uses*

.............. 9 Table 2. Taxonomic Groups, Test Species and Acute Toxicity Classification for Assessing Ecological Risks of Sulfoxaflor to Non

- target Organisms

................................ ........................... 18 Table 3. Summary of assessment and measurem ent endpoints for Sulfoxaflor

........................... 27 Table 4. Crop use patterns proposed for sulfoxaflor; Ground or aerial for all uses except for turf
and non

- commercial ornamentals (ground application)*

................................ ............................. 29 Table 5. Physical and chemical properties of Sulfoxaflor

................................ ............................ 30 Table 6. Fate properties of sulfoxaflor parent and its major degradate X

- 474 in a biotic systems 32 Table 7. Fate properties of sulfoxaflor parent and major degradate X

- 474 in biotic systems

..... 33 Table 8. Parent degra dation products for systems described in Table 7, above

........................... 34 Table 9. Selected environmental degradates of sulfoxaflor

................................ .......................... 36
Table 10. Fiel d dissipation half

- lives (DT50 in days) for sulfoxaflor from the top 6” of the soil and the entire soil profile (0

- 36”)

................................ ................................ ................................ .. 38 Table 11. Field dissipation half

- lives (DT50) for major degradate X

- 474 from the top 6” of the soil and the entire soil profile (0

- 36”)

................................ ................................ ........................... 39 Table 12. Transport properties Sulfoxaflor and its degradates

................................ ..................... 40
Ta ble 13. Summary of analytical methods (residue) for soil, water and air (method type for all analytes= LC/MS/MS)

................................ ................................ ................................ .................. 41 Table 14. Crop use patterns proposed for sulfoxaflor (Ground or aerial is permi tted for all uses (refer to exceptions stated below this Table for Turf and ornamentals)

................................ ....... 48 Table 15. List of scenarios and application parameters used in modeling

................................ ... 49 Table 16. Summary of PRZM/EXAMS input parameters for modeling Sulfoxaflor parent and
residues of interest

................................ ................................ ................................ ........................ 50 Table 17. Surface water EECs (μg/L) of the TTR for Su lfoxaflor use patterns

........................... 53 Table 18. Pore water EECs (μg/L) of the TTR for Sulfoxaflor use patterns

................................ 53 Table 19. Sediment EECs (μg/kg) for scenarios giving the highest and lowest pore water EECs 54 Table 20. EECs for watercress use when watercress beds are drained prior to, during and after pesticide application sulfoxaflor

................................ ................................ ................................ ... 59 Table 21. Input parameters used in T

- REX v1.5 to determine terrestrial EECs for the maximum sulfoxaflor spray application scenarios.

................................ ................................ ........................ 60 Table 22. Summary of sulfoxaflor toxicological endpoints for aquatic organisms

...................... 62 Table 23. Summary of sulfoxaflor toxicological endpoints for terrestrial organisms.

................. 66 Table 24. Risk Presumptions for Aquatic Animals

................................ ................................ ...... 72 Table 25. Risk Presumptions for Terrestrial Vertebrate Animals

................................ ................. 72 Table 26. Risk Presumptions for Terrestrial Invertebrate Animals

................................ .............. 72 Table 27. Risk Presumptions for Plants

................................ ................................ ........................ 72
Table 28. Maximum acute and chronic risk quotients for freshwater and saltwater fish based on
total residues of interest

................................ ................................ ................................ ................ 73 Table 29. Maximum acute and chronic risk quotients for freshwater and saltwa ter Invertebrates
based on total residues of interest

................................ ................................ ................................ . 73 Table 30. Acute risk quotients for saltwater invertebrates using refined EECs based on total toxic
residues of concern

................................ ................................ ................................ ....................... 74vi Table 31. Maximum acute and chronic risk quotients for freshwater and saltwater benthic
invertebrates based on total residues of interest

................................ ................................ ........... 75
Table 32. Risk quotients for benthic Invertebrates using refined EECs based on total toxic
residues of concern

................................ ................................ ................................ ....................... 75 Table 33. Maximum acute and chronic risk quotients for non

- vascular and vascular aquatic

p lants

................................ ................................ ................................ ................................ ............. 76
Table 34. Maximum acute dose

- based risk quotients for mammals

................................ ............. 77
Table 35. Maximum chronic diet

- based risk quotients for mamm als

................................ .......... 78
Table 36. Chronic dose

- based RQ values for mammals

................................ ............................... 78
Table 37. Acute dose

- based risk quotients for birds

................................ ................................ ..... 79
Table 38. Maximum acute diet

- based risk quotients for birds

................................ ...................... 80
Table 39. Maximum chronic diet

- based risk quotients for birds

................................ .................. 80 Table 40. Tier I exposure values of honey bees to pesticides applied via foliar applications

...... 84 Table 41. Maximum reported residues (ppm) of sulfoxaflor in pl ant and hive materials from
various field studies

................................ ................................ ................................ ...................... 84 Table 42. Estimated consumption rates of pollen, nectar and royal jelly by larval honey bees

... 85 Table 43. Estimated consumption rates of pollen, nectar and royal jelly by adult honey bees

.... 86 Table 44. Refined Tier 1 oral risk quotients for honey bees using maximum reported

co ncentrations in pollen and nectar

................................ ................................ ............................... 87 Table 45. Summary of aquatic animal risk profile for sulfoxaflor

................................ ............... 89 Table 46. Summary of the avia n and mammalian risk profile for sulfoxaflor

............................. 90 Table 47. Summary of Tier 2 colony

- level studies conducted with sulfoxaflor

......................... 101vii VI. Appendices Appendix A

. Environmental Fate and Transport Data Appendix B

. T

- REX Example Output and Parameterization Appendix C

. Ecological Effects Data Study Summaries Appendix D

. Supporting Material for Bee Risk Assessment Appendix E

. SIP and STIR Model Results8 

### 1. **E XECUTIVE**  

### S **UMMARY**

1. 1 . Nature of Chemical Stressor

Sulfoxaflor ( N

- [methyloxido[1

- [6

- (trifluorome thyl)

- 3

- pyridinyl]ethyl]

- lambda 4

- sulfanylidene] )
is a new class of insecticide and is currently the only member of the sulfoxamine subclass of
neonicotinoid insecticides

. 1 It is considered an agonist o f the nicotinic acetylcholine receptor (nAChR) and exhibits excitatory responses including tremors, followed by paralysis and mortality in target insects

. In laboratory experiments, s ulfoxaflor has been highly efficacious against target insects that displ ay resistance to neonicotinoid s such as imidacloprid, which is classified by the Insect Resistance Action Committee ( IRAC ) as subclass 4A

. Sulfoxaflor
consist s of two diastereomers in a ratio of approximately 50:50 with e ach diastereomer
consist ing of two enantiomers

.

Sulfoxaflor is formulated as suspensions concentrate and water dispersible granules and is proposed for application as a liquid spray on a variety of crops. The proposed crops include beans, berries, canola, citrus, cotton, fruits (pome/ston e), ornamentals, grains “small”, soybeans, tree nuts, turf, vegetables (brassica “leafy” bulb, cucurbits, fruity including okra, leafy, and root & tuber) and watercress . Sulfoxaflor is systemically distributed in plants

. The chemical acts through both cont act action and ingestion and provides both rapid knockdown (symptoms are typically observed within 1

- 2 hours of application) and residual control (generally provides from 7 to 21 days of residual control).

Transformation products of sulfoxaflor in the env ironment include: X11719474 (X

- 474 ; “ major

to dominant ” ) , X11579540 (X

- 540 ; “minor to major” ) , and X11579457 (X

- 457 ; “minor” )

. Following consideration of exposure a nd toxicity for the residues of interest (that is parent, X

474 and X

- 540)

, the stressor of concern is defined as follows:

(1) For aquatic organisms: parent sulfoxaflor plus its degradate, X

- 540 ; and

(2) For terrestrial organisms: parent sulfoxaflor only

.

With the exception of X

- 474, this assignment of stressors of concern for ecological risk is

con sistent with the risk assessment approach used by the Health Effects Division for sulfoxaflor ( D396249 )

. For terrestrial and aquatic ecological receptors, available evidence indicates that the
X

- 474 degradate does not share the same MOA as the parent and i s much less toxic based on measures of effect relevant to ecological risk assessment

. Detailed data and information concerning this decision are presented in the problem formulation section of this document.

1 http://www.irac

- online.org/eClassification/9 1.2 Potential Risks to Non

- target Organisms

Table 1 provide s a summar y of the environmental risk conclusions for aquatic and terrestrial organisms, based on risk quotient (RQ) values and whether they ex ceed levels of concern (LOCs) for Federally

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

- listed species.

Table 1

. Summary of Ecological Risk Conclusions for the Proposed Sulfoxaflor Uses*

Taxonomic Group Summarized Risk Characterization and Major Uncertainties

Fish and Aquatic
Invertebrate s (freshwater and saltwater) The potential for acute or chronic risk is considered low, as acute or chronic RQ
values do not exceed the risk to lis ted species LOC of 0.05

.

Aquatic and Terrestrial
Plants The potential for risk is considered low, as RQ values do not exceed the LOC
values for listed and non

- listed aquatic or terrestrial plants.

Birds ** A potential for acute risk to birds is identifi ed. Specifically, acute, dose

- based RQ values calculated using a refined dissipation half

- life (DT 50 ) exceed the risk to listed species LOC of 0.1 for at least one avian dietary category and size class
across all uses. This risk finding is uncertain becau se the acute toxicity endpoint used to derive the avian RQ values represents a “non

- definitive” endpoint and is
based on a threshold for treatment

- related increases in regurgitation. Acute and
chronic diet

- based RQ do not exceed applicable LOCs.

Mammals A potential for chronic risk to mammals is identified. Specifically, chronic dose

based RQ values up to 3.8 were determined using a refined DT 50 and exceed the risk to listed species LOC of 0.1 for at least one mammalian dietary category and
size class ac ross all uses. For some crops, information from residue

- decline trials indicates relatively short half lives ( e.g., a few days), particularly on foliage. For these crops, there is uncertainty regarding whether the relatively short duration of

exposure ex pected in the field would elicit similar reproductive effects as the chronic, 2

- generation study with the rat where animals are fed treated diets continuously.

Bees A potential for risk to honey bees is identified based on Tier 1 assessment results.
Tier 1 a cute oral RQ values range from < 0.8 to 5.7 across all larval and adult castes
examined

. Results from Tier 2 semi

- field studies indicate direct effects of
sulfoxaflor on adult foragers is likely to be short

- lived at application rates of 3

- 67% of the sing le maximum rate proposed for the US. These studies were unable to preclude risk to developing brood or long

- term colony health from the proposed sulfoxaflor applications due to limitations associated with the ir design and conduct

. * includes: Citrus, Fru its

- Pome, Fruits

- Stone, Ornamentals, Tree nuts, Turf grass; (Beans, Berries, Soybeans, Veg.

- Brassica, Veg.

- Bulb, Veg.

- Leafy, Veg.

- Root/Tuber, Veg.

- Fruiting, Veg.

- Cucurbit, Watercress, Cotton, Canola and
Grains

* * In absence of data, birds are used as a sur rogate for terrestrial phase amphibians and reptiles.10 1.3 Conclusions

- Exposure Characterization

Sulfoxaflor has a low potential for volatilization from dry and wet surfaces (vap or pressure= 1.9
x 10 - 8 torr and Henry’s Law constant= 1.2 x 10 - 11 atm m 3 mole - 1 , respectively at 25 °C). The chemical is characterized by a water solubility ranging from 550 to 1,380 ppm. Partitioning
coefficient of s ulfoxaflor from octanol to water (K ow = 6 ) suggests low potential for bioaccumulation in aquatic organisms such as fish.

Sulfoxaflor reaching the soil system is subject ed to rapid aerobic bio

- degradation (t 1⁄2 <1 day) while that reaching foliage may enter the plant tissue and persist much long er. Sulfoxaflor ha s shown to be stable to hydrolysis/ photolysis on soil and in aquatic environments

. In field studies,

s ulfoxaflor ha s shown similar vulnerability to aerobic bio

- degradation in nine out of ten terrestrial field dissipation studies on bare

- ground /cropped plots (half

- lives were <2 days in nine cropped/bare soils in CA, FL, ND, ON and TX and was 8 days in one bare ground soil in TX )

.

The c hemical can be characterized by very high to high mobility (K foc ranged from 11

- 72 mL g 1 ). Rapid soil degradation is expected to limit chemical amounts that may potentially leach and contaminate ground water. Contamination of groundwater by sulfoxaflor will only be expected when excessive rain occurs within a short period (few days) of multiple application s in vulnerable sandy soils. Contamination of surface water by sulfoxaflor is expected to be mainly related to drift and very little due to run

- off. This is because drifted sulfoxaflor that reaches aquatic systems is expected to persist while that reaching the soil system is expected to degrade quickly with slight chance for it to run

- off.

In contrast to sulfoxaflor parent, the major degradate X

- 474 and two other degradates ( X

- 540
and X

- 457 ) are expected to be highly persistent in aerobic soil/aquatic sy stems. Adsorption data for these degradates indicate that they can be characterized by very high to high mobility for X

474 (K foc ranged from 7

- 68 mL g - 1 ) and very high mobility for X

- 457 and X

- 540 (K foc ranged
from 2

- 44 mL g - 1 for X

- 4 57 and K foc ranged from 1

- 25 mL g - 1 for X

- 540 ). Both surface and ground water contamination is expected f rom these three degradates following leaching drift/run

off events. The major degradate X

- 474 is expected to dominate the exposure resulting from use
of sulfoxaflor.

1. 4 Conclusions

- Effects Characterization

Based on available data, s ulfoxaflor is slightly toxic to practically non

- toxic to fish and freshwater water column dwelling aquatic invertebrates on an acute exposure basis. It is also practically non

- toxic to aquatic plants (vascular and non

- vascular). Sulfoxaflor is highly toxic to saltwater invertebrates (mysid shrimp; Americamysis bahia ) on an acute exposure basis. The NOAEC for chronic toxicity of sulfo xaflor to freshwater benthic insects (midge, Chironomus riparius ) is 0.037 mg a

. i

. /L in porewater . The high toxicity of sulfoxaflor to mysid shrimp and
benthic aquatic insects relative to the water flea ( Daphnia magna ) is consistent with the toxicity prof ile of other insecticides with similar MOAs on the insect nAChR such as neonicotinoid
insecticides.11 For birds and mammals, sulfoxaflor is classified as moderately toxic to practically non

- toxic on an acute exposure basis. The threshold for chronic toxici ty (NOAEL) to birds is 200 ppm and that for mammals is 100 ppm in the diet. Sulfoxaflor did not exhibit deleterious effects to terrestrial plants at or above its proposed maximum application rates.

For bees, sulfoxaflor is classified as very highly toxic with acute oral and contact LD 50 values of 0.05 and 0.13 μg a

. i

. /bee, respectively

, for adult honey bees ( Apis mellifera ). For larvae, a 7

- d
oral LD 50 of >0.2 μg a

. i

. /bee was determined (45% mortality occurred at the highest treatment of
0.2 μg a

. i

. /bee )

. Its primary metabolite (X

- 474) is practically non

- toxic to the honey bee . This lack of toxicity is consistent with the cyano

- substituted neonic otinoids where similar cleavage of the cyanide group appears to eliminate their insecticidal activity. The ac ute oral toxicity of sulfoxaflor to adult bumble bees ( Bombus terrestris ) is similar to the honey bee; whereas its acute contact toxicity is about 20X less toxic for the bumble bee. Sulfoxaflor did not
demonstrate substantial residual toxicity to honey be es exposed via treated and aged alfalfa ( i.e

., mortality was < 15% at maximum application rates ).

A detailed analysis of six available Tier 2 semi

- field (tunnel) studies was conducted in order to
confirm or refute the risks identified from the Tier 1 asses sment on honey bees. Five of the six
semi

- field studies used application rates ranging from 3 to 67% of the single maximum rate o f 0.133 lb a.i./A proposed for the US. The one semi

- field study that used maximum US application rates was intended for quant ifying residues in plant matrices, and thus, has limited biological effects information.

In considering the available information from the semi

- field tunnel studies, the following
conclusions were reached:

• Adult mortality, flight activity, behavioral abn ormalities. A t the application rates used (3

- 67% of US maximum), the direct effects of sulfoxaflor on adult forager bee mortality, flight activity and the occurrence of behavioral abnormalities is relatively short

- lived, lasting 3 days or less. Direct eff ects are considered those that result directly from interception of spray droplets or dermal contact with foliar residues. The direct effect of sulfoxaflor on these measures at the maximum application rate in the US is presently not
known.

• Development of Brood. The effect of sulfoxaflor on brood development is considered
inconclusive due to numerous limitations in the design and conduct of the available
studies. These limitations include poor performance of control hives, lack of (or short) post

- applica tion observation period in order to detect brood effects, and lack of a
concurrent control.

• Colony Strength. When compared to controls hives , the effect of sulfoxaflor on honey
bee colony strength when applied at 3

- 32% of the US maximum proposed rate was not apparent in most cases. When compared to hives prior to pesticide application,

s ulfoxaflor applied to cotton foliage up to the maximum rate proposed in the US resulted12 in no discernible decline in mean colony strength by 17days after the first applica tion

. Longer

- term results we re not available from this study nor w ere concurrent control s included.

1.5 Data Gaps and Uncertainties

1.5.1 Environmental Fate

Submitte d environmental fate data meet the requirements for this screening level assessment
with no fate and transport data gaps

.

1.5.2 Ecological Effects

The primary uncertainty in the ecological effects data for sulfoxaflo r is lack of a reliable Tier 2
semi

- field study for assessing impacts on honey bee colony strength and brood development in
accordance with OECD

- established test guidelines

. It is further noted that the high variability in
sulfoxaflor residues from the cot ton residue study and the nature of the cotton flowering introduces uncertainty in the extrapolation of these residue data to other crops. Therefore, additional data on the nature and magnitude of sulfoxaflor residues in one or more pollinator

attractive crops would be needed to address this source of uncertainty. Other uncertainties include lack of definitive toxicity endpoints for passerine birds and larval honey bees.13 

### 2. **P ROBLEM**  

### F **ORMULATION**

Problem formulation provides a strategic framework for the risk assessment. It sets the objectives for the risk assessment and provides a plan for analyzing the data and characterizing the risk (US EPA 1998). By identifying the important components of the risk assessment

process , it f ocuses the assessment on the most relevant ecological receptors (species), chemical properties, exposure routes, and endpoints. The structure of this risk assessment is based on guidance contained in U.S. EPA’s Guidance for Ecological Risk Assessment (USE PA 1998) and is consistent with procedures and methodology outlined in the Overview Document (USEPA 2004).

2.1 Nature of the R egulatory action

The purpose of this assessment is to evaluate the environmental fate and ecological risks for the proposed n ew registration of the chemical sulfoxaflor. Under Section 3 of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), U.S. EPA is required to evaluate the potential of new pesticides (and new pesticide uses) to cause adverse effects to the envir onment. Potential effects to listed species (species on the Federal list of endangered and threatened wildlife and plants) are also considered under the Endangered Species Act in order to ensure that the registration of sulfoxaflor is not likely to jeopar dize the continued existence of such listed species or adversely modify their habitat. To these ends, this assessment follows U.S. EPA’s guidance on conducting ecological risk assessments and policies for assessing risk to non

- target and listed organisms ( U.S. EPA, 1998 and U.S. EPA, 2004).

2.2 Nature of the Chemical Stressor

2.2.1 Overview of Pesticide Usage

Sulfoxaflor is proposed for appli cation as a liqui d spray applied by ground and aircraft equipment on a variety of crops including beans, berries, canola, citrus, fruits (pome/stone), ornamentals, grains “small”, soybeans, tree nuts, turf, vegetables (brassica “leafy” bulb, cucurbits, fruity including okr a, leafy, and root & tuber) and watercress. Sulfoxaflor is to be applied to watercress foliage growing in beds completely drained prior to, during and after the application

. Aphids appear to be the main t arget pests for watercress. Giv en the fact that

wate rcress is harvested for its foliage and mostly propagated by vegetative parts, it is not expected that the chemical will be applied during bloom except in beds used for seed production

.14 2

. 2

. 2 Pesticide Type, Class, and Mode of Action

Sulfoxaflor is a new class of insecticide as it is currently the only member of the sulfoxamine
subclass of the neonicotinoid insecticides according to the Insecticide Resistance Action Committee (IRAC)

. 2 Other subc lasses of neonicotinoid insecticides include the cyano

substituted ( e.g ., acetamiprid and thiacloprid) and the nitroguanidine

- substituted neonicotinoids ( e.g ., imidacloprid, thiamethoxam, clothianidin and dinotefuran) Its common mode of
action (MOA) as a neonicotinoid is that of an agonist of the nicotinic acetylcholine receptor (nAChR) whereby it exhibits excitatory responses including tremors, followed by paralysis and mortality in target insects (Zhu et al. 201 1 ). Sulfoxaflor has also not demonstrated cross

resistance in strains of whitefly and brown planthopper that were bred to be highly resistant to the nitroguanidine subclass neonicotinoid such as imidacloprid (Babcock et al. 2010 ; Zhu et al

. 201 1 ); this lack of cross resistance is believed to be p artially due to sulfoxaflor’s lack of susceptibility to the metabolic mechanisms that are considered responsible for insect resistance to neonicotinoids ( e.g ., upregulation of monooxygenase [CYP6G1] enzymes). Zhu et al. also indicate the specific nature su lfoxaflor binding to the nAChR likely differs from that of other neonicotinoid subclasses. As a result, the IRAC classifies sulfoxaflor in its own subclass (subclass C; sulfoxamines) under Group 4 (nicotinic acetylcholine receptor agonists), whereas nitrog uanidine

- substituted neonicotinoids such as imidacloprid, acetam i prid and thiamethoxam
are in subclass A

.

2. 2.3 Overview of Physicochemical, Fate, and Transport Properties

Sulfoxaflor is c haracterized by a water solubility ranging from 550 to 1,380 ppm with low potential for volatilization from dry and wet surfaces. Partitioning coefficient of s ulfoxaflor from octanol to water (K ow ) suggests low potential for bioaccumulation in aquatic orga nisms such as
fish. According to the registrant, sulfoxaflor is intended to act through both contact action and ingestion and provides both knockdown (symptoms are typically observed within 1

- 2 hours of application) and residual control (generally provides from 7 to 21 days of residual control).

Sulfoxaflor is a systemic insecticide which displays translaminar movement when applied to foliage. Movement of sulfoxaflor within the plant follows the direction of water transport within the plant ( i.e., xylem mobile) as indicated by phosphor translocation studies in several plants including cabbage, pepper and cotton (MRID 48445804). Example phos phor images for cotton from this study are shown in Figure 1

. From zero t o 72 hours, Panel A and B of Figure 1
indicate little movement of 14 C

- labeled sulfoxaflor when applied to the cotton leaf (mainly outward to leave edge). In contrast, Panel C and D of Figure 1 indicate that when sulfoxaflor is applied to the plant stem, it is transported upward to all stem and leaf tissues along the water transpiration stream

. Thus, while foliar applications to leaf surfaces would likely result in
localise d (translaminar) transport, they would also likely involve contact with lower portions of the plant (stems) which would result in ‘upward’ transport throughout the plant.

2 http://www.irac

- online.org/eClassificat ion/15 A. 0 hours ( leaf application ) B. 72 hours ( leaf application ) Phosphor image Dried plant Phosphor image Dried plant

C. 0 hours (Stem application ) D. 72 hours (Stem application ) Phosphor image Dried plant Phosphor image Dried plant

Figure 1

. Results fro m cotton plant translocation study with sulfoxaflor applied to leaf (Panel A&B) and stem (Panel C&D); MRID 48445804

Sulfoxaflor is resistant to hydrolysis and photolysis but transforms quickly in soils

. In contrast, sulfoxaflor reaching plant foliage ente rs into plant tissue and is metabolized into X

- 4 74 and X

061. Furthermore, sulfoxaflor reaching aquatic systems by drift is expected to degrade rather slowly.

2.2

. 4 Stressor Source
, Intensity and Identity

Sulfoxaflor i s formulated as a suspension concentrate (SC) and water dispersible granules (WDG) and i s proposed for application as a liquid spray on variety of crops. It is proposed to be applied to foliage using ground, airblast and/ or aerial spray equipments. The max imum single rate of application for s ulfoxaflor formulations ranges from 0.0 43 to 0. 133 lb a.i/A w ith a
maximum yearly rate s of 0. 090 to 0.266 lb a.i/A/ y ear applied in two or three applications at intervals ranging from 5 to 14 days

.16 In characterizing t he nature of this stressor, both exposure and toxicity of the residues of interest ( parent , X

- 474 and X

- 540 ) and other degradates are considered for both aquatic and terrestrial systems

.

1. Exposure Considerations : For understanding the source and intens ity of sulfoxaflor in aquatic systems

, a conceptual diagram is used to understand the distribution of expected parent and associated degradates in surface water and ground water ( Figure 2 ).

Figure 2

. Diagram summarizing distribution of expected residues of interest constituents in
surface water and ground water.

As shown in Figure 2

, the s ource and intensity of the parent and degradates are expected to be controlled by fate processes dominant in various compartments of the natural environment where the chemical s are expected to reach. These processes include run

- off, leaching and sp ray drift. Partition ing of sulfoxaflor to air is not expected to be important due to the low vapor pressure and Henry’s Law constant for s ulfoxaflor

. Exposure in surface water results from drifted parent as only minor amounts is expected to run

- off only wh en rainfall and/or irrigation immediately follow application . For the degradate X

Plant Foliage: Parent (major) Application of Sulfoxaflor Parent

Drift

Direct Application Aquatic Systems: Parent (majo r) Wash

- off

Slow Aerobic/Anaerobic Aquatic Degradation Soil System: Parent (major)

Expecte d soil concentration following: Fast degradation of parent and slow degradation of X

- 474 in the soil system Parent (major) (The major un

degraded amounts +
Minor amounts from

run

- off X

- 474 (major) (The minor
amounts from parent degradation)

+ Major amou nts

from Run

- off Parent (m inor) Run

- off

X

- 474 (major) Run

- off

X

- 540 (minor) (From run

- off only) X

- 540 ( minor )

Surface Water Ground Water Le a ching Run

- off17 474 , major amounts are expected due to run

- off of degraded parent compound in the soil

. For the degradate X

- 540

, minor amounts are expected from run

- off alone.

I n terrestri al systems, the source of the pesticide stressor is its foliar application that is expected to mostly reach the foliage and partly reach the soil system as parent.
S ulfoxaflor reaching the foliage (including plant stems) is expected to partially move into the plant tissue and degrade over time

. However, the portion of the parent pesticide that is left on the foliage is expected to stay as parent

. The degradate X

- 474 is also considered relevant to exposure in terrestrial systems, due to biotransformation of parent in soil and subsequent uptake by plants. X

- 540 is not a major metabolite in plants (observed < 1% of TRR in lettuce metabolism studies and not in all in the other plant metabolism studies).

2. Toxicity Considerations : In aquatic systems, organ isms are expected to be exposed to parent sulfoxaflor and the degradation products X

- 474 and X

- 540 ( Figure 2 ).
C omparative toxicity data for one freshwater fish and one freshwater invertebrate species
indicate that sulfoxaflor and X

- 474 are both practically non

- toxic on an acute exposure basis ( LC 50 values are all > 100 mg a.i/L ; See Section 4 for additional discussion ). No chronic toxicity data are available for comparing the toxicity of sulfoxaflor and its degrada tes to aquatic organisms. Toxicity data for mammals and birds indicate that X

474 is less acutely toxic compared to parent sulfoxaflor, while the minor degradate, X

540 , is about 2X more acutely toxic than parent based on mammalian acute LD 50 data.
There is also indication for increased toxicity of X540 compared to parent in a subchronic mammalian dietary study; however

, the endpoints quantified (liver weight, mitotic figures) are not quantitatively linked to assessment endpoints used for ecological risk

assessment (e.g., survival, growth, reproduction)

.

For terrestrial organisms, available data indicate that the degradate X

- 474 is much less toxic than the parent to birds, mammals, and insects (honey bee) on an acute exposure
basis (See Section 4 for d etails)

. Furthermore, results from the Health Effects Division
assessment of residues of concern indicate the mode of action of sulfoxaflor is not
conserved with X

- 474 (D398294) . Regarding the degradate X

- 061, mammalian acute toxicity data indicate it is about 2X less toxic than the sulfoxaflor parent and practically

non

- toxic to the honey bee. Although X

- 540 is more acutely toxic than parent sulfoxaflor to the rat, X

- 540 is not a major metabolite in plants as indicated above.

3. Stressors of Concern. For aquatic organisms, the stressor of concern to aquatic organisms is considered to be “sulfoxaflor parent + X

- 540 , assuming equal toxicity as parent sulfoxaflor. The equal toxicity assumption between parent and X

- 540 is based on the similarity in their acute oral toxicity to mammals (i.e., within a factor of two). Although X

- 474 is considered a major degradate, it is not included in the stressor for aquatic organisms because of its lack of acute toxicity, expectation that it does not share
the same MOA a s parent due to loss of cyano

- substitution, and QSAR results indicating its low toxicity.

For terrestrial animals (birds, mammals, and terrestrial invertebrates), the stressor of concern is defined as parent sulfoxaflor only . This definition considers the lower18 potency of the two primary degradation products in plants (X

- 474 and X

- 061) and lack of significant exposure expected for X

- 540. This stressor definition is also consistent with HED’s residue of concern findings for defining residue tolerance va lues in crops. For terrestrial plants, the stressor is defined as sulfoxaflor only given that no comparative toxicity data for plants are available for the parent or degradates and that parent chemical was not toxic to terrestrial plants at or above the p roposed maximum application rates.

2. 3 Ecological Receptors

The receptor is the biological entity that is exposed to the stressor (US EPA, 1998). Aquatic receptors potentially at risk include (but are not limited to): fish, amphibians, invertebrates ( e .g ., aquatic insects, mollusks, crustaceans, and worms), vascular and nonvascular aquatic plants. Terrestrial receptors potentially at risk include (but are not limited to): birds, mammals, reptiles, amphibians, terrestrial invertebrates ( e.g ., insects, w orms, arachnids), and plants.

Consistent with the process described in the Overview Document (US EPA, 2004), this risk assessment uses the surrogate species approach in its evaluation of sulfoxaflor. Toxicological data generated from surrogate test speci es, that are intended to be representative of broad taxonomic groups

, are used to extrapolate to potential effects on a variety of species (receptors) included under these taxonomic groupings.

Acute and chronic toxicity data from studies submitted by pe sticide registrants along with the available open literature are used to evaluate potential direct effects of sulfoxaflor to the aquatic and terrestrial receptors identified in this section. Since sulfoxaflor is a new active ingredient, the availability o f open literature information on its toxicity is expected to be limited. The open literature studies are identified through EPA’s ECOTOX database ( http://cfpub.epa.gov/ecotox/ ), which employs a literature search engine for locating chemical toxicity data for aquatic life, terrestrial plants, and wildlife. The evaluation of both sources of data can also provide insight into the direct and indirect effects of sulfoxaflor on biotic communities due to loss of species that are sensitive to the chemical and changes in structure and functional characteristics of the
affected communities.

A summary of the taxonomic groups and the surrogate species tested to help understand potential acute ecological effects of pesticide s to non

- target species is provided in Table 2 . In addition, the table provides a preliminary overview of the potential acute toxicity of sulfoxaflor by providing the acute toxicity classifications.

Table 2

. Taxonomic Groups, Test Species and Acute Toxicity Classification for Assessing Ecological Risks of Sulf oxaflor to Non

- target Organisms
Taxonomic Group Example(s) of Surrogate Species Acute Toxicity Classification

Birds 1 Mallard duck ( Anas platyrhynchos ) Bobwhite quail ( Colinus virginianus ) Zebra finch ( Poephila guttata) P ractically non

- toxic Slightly toxic Moderately toxic

Mammals Laboratory rat ( Rattus norvegicus ) Slightly toxic19 Taxonomic Group Example(s) of Surrogate Species Acute Toxicity Classification

Insects Honey bee ( Apis mellifera L. ) Bumble bee ( Bom bus terrestris ) Very highly toxic Moderately toxic

Freshwater fish 2 Bluegill sunfish ( Lepomis macrochirus ) Rainbow trout ( Oncorhynchus mykiss ) Carp ( Cyprinus carpio) Practically non

- toxic

Freshwater invertebrates Water flea ( Daphnia magna ) Practically n on

- toxic

Estuarine/marine fish Sheepshead minnow (Cyprinodon variegatus) Practically non

- toxic

Estuarine/marine

invertebrates Mysid shrimp ( Americamysis bahia ) Eastern oyster ( Crassostrea virginica) H ighly toxic Practically

- non toxic

1 In absence of da ta, birds are used as surrogates for terrestrial

- phase amphibians and reptiles.

2 In absence of data, freshwater fish may be surrogates for aquatic

- phase amphibians.

2. 4 Ecosystems at Risk

The ecosystems at potential risk from sulfoxaflor are extensive in scope due to the wide geographic distribution of potential sulfoxaflor application sites. In general terms, terrestrial ecosystems potentially at risk could include the treatment areas directly and adjacent areas that may receive drift or runoff. This could include the treatment area itself as well as other cultivated fields, fencerows and hedgerows, meadows, fallow fields or grasslands, woodlands, riparian habitats and other uncultivated areas.

Aquatic ecosystems potentially at risk include water b odies adjacent to (or downstream from) the treatment area and might include impounded bodies such as ponds, lakes, reservoirs and wetland areas, or flowing waterways such as streams and rivers. For uses in coastal areas, aquatic habitat
also includes marin e ecosystems, including estuaries and salt marshes.

2. 5 Assessment Endpoints

Assessment endpoints represent the actual environmental value that is to be protected, defined by an ecological entity (species, community, or other entity) and its attribute or characteristics (US EPA, 1998). For sulfoxaflor, the ecological entities may include the following: birds, mammals, freshwater fish and invertebrates, estuarine/marine fish and invertebrates, terrestrial plants, insects, and aquatic plants and algae. The attributes for each of these entities may include growth, reproduction, and survival and are discussed further in Section 2.7: ( Analysis Plan)

.

2. 6 Conceptual Model

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 have a s ource, a release mechanism, an environmental transport medium, a point of exposure for ecological receptors, and a feasible route of exposure.20 A conceptual model is used in this risk assessment to provide a written and visual description of the predicted relationships between sulfoxaflor, potential routes of exposure, and the predicted effects for the assessment endpoint. A conceptual model consists of two major components: risk hypotheses and a conceptual diagram (US EPA, 1998).

2. 6. 1 Diagram

Based on the preliminary iterative process of examining fate and effects data, the conceptual model or the risk hypothesis model for spray application to agricultural crops has been established, refined and included in Figure 3 , Figure 4 , and Figure 5

, respectively . In establishing the diagram for the conceptual model it was necessary to go through an iterative

proces s to identify: (1) likely stressors/exposure pathways and (2) organisms that are most relevant and applicable to this assessment.

Primary exposure routes for aquatic organisms include spray drift and runoff of sulfoxaflor (and
its degradates) into nearby bodies of water. Once in the water, the primary exposure route to aquatic organisms is direct uptake across respiratory membranes (animals) and roots/integument (plants). Dietary uptake (ingestion) is not considered an important exposure pathway given t he very low bioaccumulation potential of sulfoxaflor.

Primary exposure routes for terrestrial organisms (except bees) include direct contact with spray droplets, dermal contact with foliar residues, uptake from soil (plants and soil invertebrates) and

con sumption of contaminated foliage (herbivorous animals). Inhalation is not considered an exposure route of concern based on results of the Screening Tool for Inhalation Risk (STIR ; version 1.0 ) model ( Appendix E ). Consumption of contaminated drinking water is a potential exposure route of concern based on results of Screening Imbibition Program (SIP ; version 1.0; Appendix E ). However, additional refinements are needed to de termine if actual risks result from this exposure pathway. At this time, EFED has does have available an approved modeling tool to enable refinements to the SIP screening model.

For managed bees (e.g., honey bees), the primary exposure routes of concer n include direct contact with spray droplets, dermal contact with foliar residues, and ingestion through consumption of contaminated pollen

, nectar and associated processed food provisions ( e.g., brood food, royal jelly, propolis). Exposure of hive bees v ia contaminated wax is also possible, although difficult to quantify at this time. Exposure of bees through contaminated drinking water is not expected to be nearly as important as exposure through direct contact or pollen and nectar (USEPA, 2012).21 Fig ure 3

. An ecological conceptual model for aquatic exposure from spray application of
sulfoxaflor * Exposure of piscivorous wildlife via ingestion of aquatic organisms is not an exposure pathway of concern for sulfoxaflor Stressor

Source

Receptors

Attribute Change Foliar spray application of sulfoxaflor to crops

Spray drift

Aquatic animals
Invertebrates
Vertebrates*

Individual organisms
Reduced survival Reduced growth Reduced reproduction Food chain Reduction in algae and

vascular plants Reduction in prey Modification of PCEs

related to prey availability Habitat integrity Reduction in primary productivity
Reduced cover Community change Modification of PCEs related to

habitat Surface water/ Sediment Runoff

Aquatic Animals
Invertebrates
Vertebrates Exposure
Media

Uptake/gills or integument

Ingestion Ingestion Atmospheric transport

Wet/dry deposition Soil Leaching to Groundwater

Uptake/gills or integument

Aquatic Plants
Non

- vascular
Vascular Uptake/cell, roots, leaves Riparian plants
terrestrial

exposure pathways see Figure 222 Figure 4

. An ecological conceptual model for terrestrial exposure from spray application of
sulfoxaflor * See Figure 3 for a detailed conceptual model of sulfoxaflor risks to honey bees. Stressor

Source

Attribute Change Foliar spray application of sulfoxaflor to crops

Direct application Spray drift

Terrestrial
vertebrates* Terrestrial

Inverts*

Individual organisms
Reduced survival Reduced growth Reduced reproduction Food chain Reduction in prey and food Modification of PCEs

related to prey availability Habitat integrity Reduction in primary productivity
Reduced cover Community change Modification of PCEs related

to habitat Terrestrial plants grasses/forbs, fruit, seeds (trees, shrubs) Runoff

Terrestrial
vertebrates* Exposure Media & Receptors Soil

Ingestion Ingestion Dermal uptake/Ingestion Atmospheric transport

Root uptake/contact
Wet/dry deposition

Ingestion Leaching to Groundwater Irrigation

water

Ingestion23 Figure 5

. An ecological conceptual model for honey bee exposure from spray application of
sulfoxaflor

2.6.2 Risk Hypothesis

Risk hypotheses are specific assumptions about potential adverse effects ( i. e ., changes in assessment endpoints) and may be based on theory and logic, empirical data, mathematical models, or probability models (EPA 1998). The ensuing risk assessment will evaluate whether or not the specific risk hypotheses are supported. For fol iar applications of sulfoxaflor, the following ecological risk hypothesis is being employed for this risk assessment:

Based on the environmental fate, systemic uptake and distribution by plants and nature of foliar applications of sulfoxaflor to crops, (i ncluding its primary degradates of concern), there is a potential that terrestrial and/or aquatic organisms will be exposed when sulfoxaflor is used in accordance with the label. Consequently, considering the MOA and toxicity of sulfoxaflor, the proposed uses of sulfoxaflor have the potential to cause adverse effects upon the survival, growth, and reproduction of non

- target terrestrial and aquatic plants and animals. Stressor

Source

Attribute Change Sulfoxaflor Foliar Spray Application to Crops

Foraging Bees (workers) Hive Bees (Nurse, Worker, Drone**) Exposure
Media

Receptors Dermal Uptake &
Inhalation Residues On
Plant Surfaces Deposition onto
Plants

Residues In (On) Pollen, Nectar, Exudates, Honey Dew

Bee Brood Spray Deposition On Bees Deposition onto Soil

Residues

In Soil

Ingestion Deposition onto Surface Water

Residues in Surface

Water

Queen** Pollen & Nectar Processing, Ingestion; Comb Production Brood Provisions*

Royal Jelly Root Uptake Runoff/
Erosion Foliar Translocation

Population Size and Stability of Colonies Reduced colony strength and survival Reduced queen fecundity & brood success Reduced individual survival, behavior changes Quantity and Quality of Hive Products Reduced honey, wax, propolis production

Contribution to Pollinator Biodiversity Reduced species richness and abundance

* Brood initially rely on brood jelly and royal jelly, but later in development consume processed pollen and honey; whereas q uee ns rely solely on royal jelly. ** interception of spray droplets is also a potential route of exposure during mating and orientation flights Wax, Propolis24 2. 7 Analysis Plan

2. 7 .1 Methods for Conducting Ecologica l Risk Assessment

The primary method used to assess risk in this screening

- level assessment is the risk quotient (RQ) and follows closely methods outlined in the EPA Overview Document ( US EPA, 2004). The RQ is the risk value for the screening

- level asses sment and is the result of comparing measures of exposure to measures of effect. A commonly used measure of exposure is the estimated exposure concentration (EEC) and commonly used measures of effect include toxicity
values such as the median lethal dose to 50% of the organisms tested ( LD 50 ) , medial lethal concentration to 50% of tested organisms (LC 50 ), the no observed adverse effect level (NOAEL) 3 , and the no observed adverse effect concentration ( NOAEC ) . The resulting ratio of the point estimate of exp osure and the point estimate of toxicity, i.e., the RQ

, is then compared to a specified level of concern (LOC), which represents a threshold for concern; if the RQ exceeds the LOC, risks concerns are triggered. Risk presumptions, along with the correspond ing RQs, equations, and LOCs are summarized in
Section 5

.

Generation of robust RQs is dependent on the quality of data from both fate and toxicological studies. The adequacy of the submitted data was evaluated relative to Agency guidelines. The
follow ing identified data gaps for ecological fate and toxicity endpoints result in a degree of uncertainty in evaluating the ecological risk of sulfoxaflor

.

3 A NOAEL refers to a dose

- based toxicity endpoint whereas a NOAEC refers to a concentration based endpoint.25 2. 7 .2 Measures of Exposure

Measures of exposure are estimat es of exposure for a receptor determined by modeling or monitoring data. Measures of exposure for sulfoxaflor, in this assessment

, are obtained from modeling efforts only, since this is a new chemical and national

- scale monitoring data are not expected to be present . Exposure models used for this assessment include the suite of standard exposure models commonly used in pesticide risk assessments ( US EPA, 2004). Generally, aquatic exposure estimates are generated from E PA models and incorporate maximum pro posed

use rates , minimum application intervals, and empirically

- derived fate properties. Further details of the exposure models can be found in the Exposure Characterization section of the risk
assessment and on the web.

http://www.epa.gov/oppefed1/models/water/index.htm

Exposure to aquatic organisms is assumed to occur through direct contact with surface water contaminated by drift and/or runoff/erosion from agricu ltural fields. Aqua tic exposure
concentrations

, for all crops except watercress, in this assessment were based on EECs calculated using Tier II

- linked Pesticide Root Zone Model ( version 3.1 2 .2 Car ousel et al

. , 2005 ) and the Exposure Analysis Modeling System ( version 2.98.04 ; Burns , 1997) referred to as
PRZM/EXAMS. Model runs were executed using graphic interface ( EXPRESS or PE

- 5). For watercress, EECs were conservatively estimated using the Tier 1 Rice Model.

Measures of exposure for terrestrial mammals, birds, reptiles and amphibians similarly incorporate maximum proposed use rates

, but rely less on environmental fate properties. Terrestrial exposures were estimated using a number of methods. The Kenaga nomogram, as modified by Fletcher et al ., (Kenaga and Hoerger 1972; Fl etcher et al . 1994) is used to relate pesticide application rates to chemical residues on terrestrial food items. The surface residue concentration ( in parts per million; ppm) is estimated by multiplying the application rate (pounds active ingredient per acre ; lbs a.i./A ) by a value specific to each food item. For numerous applications for a given use, the T errestrial E xposure (T

- REX; version 1.5 .1 ) model is used with the maximum application rates and minimum application intervals allowable on the proposed labels. Degradation is considered using a first

- order decay rate dependent on a chemical

- specific foliar dissipation half

- life of 12.3 days for sulfoxaflor based on submitted residue

- decline data. The conceptual approach taken to estimate residues (uppe r

- bound and mean) in potential dietary sources for mammals and birds is presented in the model T

- REX Version 1.5 .1 available at:

http://www.epa.gov/oppefed1/models/terrestrial/index.ht m

Exposure of non

- target terrestrial and semi

- aquatic plants to sulfoxaflor is estimated using the TerrPlant model (version 1.2.2) which accounts for both spray drift and runoff as a function of application rate.26 Exposure of honey bees to sulfoxaflor is estimated using a Tiered approach as outlined in
USEPA ( 2012 ) : Draft Framework for Pollinator Risk Assessment 4 . Tier 1 of this draft framework involves estimating pesticide doses to honey bees from direct contact using an upper

bound estimate of 2.7 μ g a.i /bee per 1 lb a.i /A and an upper

- bound estimate of oral ingestion using the T

- REX model for arthropod residues. Further refinement of the oral doses is conducted using available measured pesticide residue information for pollen and nectar.
Additional information on estimation of oral and contact doses to honey bees is provided in Appendix D

.

2. 7

. 3 Measures of Effect

Measures of ecological effects are obtained from a suite of registrant

- submitted guideline studies conducted with a limited number of surrogate species. The test species are not intended to be representative of the most sensitive species but rather were selected based on their ability to
thrive under laborator y conditions. Measures of effect are based on d eleterious changes in an organism as a result of chemical exposure. Functionally, measures of effect typically used in risk assessments include changes in survival, reproduction, or growth as determined from standard laboratory toxicity tests. The focus on these effects for quantitative risk assessment is due to their clear relationship to higher

- order ecological systems such as populations, communities, and ecosystems. Although monitoring data such as adve rse effect incident reports may also be used to provide supporting lines of evidence for the risk characterization, monitoring
data are lacking for this new chemical. Over the 2012 growing season, a Section 18 emergency use was granted for application of sulfoxaflor to cotton in four states (MS, LA, AR, TN). To date, no incident reports have been received in association with the use of sulfoxaflor. However, due to the nature of ecological incident reporting, absence of incidents cannot be construed with
absence of incidents. In addition, effects other than survival, reproduction, and growth may be considered, rarely are they used quantitatively to estimate risks since, in many cases, the relationship between these effects and higher

- order processes is te nuous at best. Commonly used laboratory

- derived toxicity values include estimates of acute mortality ( e.g. , LD 50 , LC 50 ) and estimates of effects due to longer term, chronic exposures ( e.g. , NOAEC, NOAEL). The latter can reflect changes seen in mortality, reproduction, or growth. In general, for a given assessment endpoint the lowest ( i.e ., most sensitive) relevant measure of effect is used is calculating the RQ. In addition, for insect pollinators (honey bee), effects are also assessed at the colony le vel using
semi

- field and/or full

- field studies. Measurement endpoints include colony strength, foraging activity, forager mortality, and various measures of brood development.

Assessment endpoints and their respective measures of effect are listed in Table 3

.

4 http://www.epa.gov/scipoly/sap/meetings/2012/091112meeting.ht ml27 Table 3

. Summary of assessment and measurement endpoints for Sulfoxaflo r

Assessment Endpoint Measures of Exposure Measures of Effect

1. Abundance (i.e., survival, reproduction, and growth) of individuals and populations of
birds 2

. Maximum (peak)
residues on food items (foliar) 1a. Zebra finch and mallard duck acute
oral LD 50 . 1b. Mallard duck subacute dietary LC 50 . 1c. Mallard duck and bobwhite quail chronic reproduction NOAEC a nd LOAEC.

2. Abundance (i.e., survival, reproduction, and growth) of individuals and populations of
mammals. Maximum (peak)
residues on food items (foliar) 2a. Laboratory rat and mouse acute oral

LD 50 . 2b. Laboratory rat 2

- generation reproduction chro nic NOAEL and LOAEL.

3. Survival and reproduction of
individuals and communities of
freshwater fish 3 and
invertebrates. Peak EEC (acute), 21

- d &

60

- d surface water EEC (chronic) 1 3a. Rainbow trout, bluegill sunfish and carp acute LC 50 . 3b. Fathead minn ow early life stage
NOAEC and LOAEC. 3c. Daphnid acute EC 50 . 3d. Daphnid chronic reproduction NOAEC
and LOAEC. 4. Survival and reproduction of
individuals and communities of estuarine/marine fish and

invertebrates. Peak EEC (acute), 21

- d &

60

- d surface water EEC (chronic) 1 4a. Sheepshead minnow acute LC 50 . 4b. Saltwater mysid acute LC 50 .

5. Survival of individuals and
communities of freshwater and estuarine/marine benthic organisms. 21

- d pore water and
sediment EEC 1 5a. Freshwater midge subchronic NOAEC
and LOAEC. 5b. Estuarine/marine mollusk acute EC 50 based on shell deposition.

6. Perpetuation of individuals and populations of non

- target terrestrial plant species. Estimates of runoff and spray drift to non

- target

areas 6a. Monocot and dicot se edling emergence and vegetative vigor EC 25 values.

7. Maintenance and growth of individuals and populations of aquatic vascular and nonvascular plants. Peak surface water EEC 7a. Lemna gibba acute EC 50 values based on yield and growth rate. 7b. Algal ac ute EC 50 values based on cell density, biomass and growth rate.

8. Population s ize and s tability of

m anaged bee colonies; Quality of
h ive p roducts Upper bound oral and
contact dose to adult and larvae (laboratory studies) 8a. Honey bee adult acute cont act LD 50 . 8b. Honey bee adult acute oral LC 50 . 8c. Honey bee larval chronic NOAEC or

LD 10 8d. Honey bee colony level effects28 Assessment Endpoint Measures of Exposure Measures of Effect

LD 50 = Lethal dos e to 50% of the test population; NOAEC = N o

- observed

- adverse

- effect level; LOAEC =

Lowes t

- observed

- adverse

- eff ect level; LC 50 = Lethal concentratio n to 50% of the test population; EC 50 /EC 25 = Effect concentration to 50/25% of the test population.

1 Based on a 1

- in

- 10

- year return frequency.

2 According to EFED risk assessment guidance, birds may be used as surrogat es for amphibians (terrestrial phase) and reptiles.

3 According to EFED risk assessment guidance, freshwater fish may be used as surrogates for amphibians (aquatic phase).29 

### 3. **A NALYSIS** 

3.1 Use Characterization

Sulfoxaflor is propose d to be widely used in the U

. S

. to control or suppress a wide range of insect pests including aphids, plant bugs, stink bugs, whiteflies and certain scales, thrips and psyllids. The list of the proposed crop use s incl ude barley, Brassica (cole) leafy vegetables, bulb vegetables, canola (rapeseed), citrus, cotton, cucurbit vegetables, fruiting vegetables, leafy vegetables (except Brassica ), leaves of root and tuber vegetables, low growing berry, okra, ornamentals (herba ceous and woody), pistachio, pome fruits, root and tuber vegetables, small fruit vine climbing (except fuzzy kiwifruit), soybean, stone fruits, succulent, edible podded, and dry beans, tree nuts, triticale, turf grass , watercress, and wheat. Sulfoxaflor i s formulat ed as a suspension concentrate “ SC ” ( Proposed label: GF

- 2032 SC containing 2 lb a

. i/gal ) a nd as water dispersible granule “WG” ( Proposed label: GF

- 2372 WG or TransformTM WG containing 50%

a

. i by weight . Formulations are proposed to be applied as l iquid spray by ground, airblast, and
aerial into the crop foliage. The potential usage areas may be inferred from the proposed crop use patterns. The spatial extent of usage areas is expected cover large acreage s of the proposed crop land in the U

. S

. Table 4 contains a summary of all crops proposed to be treated with sulfoxaflor

.

Table 4

. Crop use patterns proposed for sulfoxaflor; Ground or aerial for all uses except
for turf and non

- commer cial ornamentals (ground application)*

Crop/Crop Group ** Crop Group(CG) Or Subgroup (SG) Max Single Rate (lb a.i./A) Max No. of Application s Max Yearly Rate (lb a.i./A) Min Intervals (days)

Beans Beans 0.090 3 0.266 7

Berries SG 13

- 07F &G 0.090 3 0.266 7

Canola (Rapeseed) SG 20A 0.043 2 0.090 14

Citrus CG 10 0.133 2 0.266 7

Cotton Cotton 0.090 3 0.266 5

Fruits: Pome CG 11 0.133 2 0.266 7

Fruits: Stone CG 12 0.133 2 0.266 7

Grains Small Grains 0.043 2 0.090 14

Ornamentals Ornamentals 0.133 2 0.266 7

Soybeans Soybeans 0.090 3 0.266 7

Tree Nuts CG 14 & P istachio 0.133 2 0.266 7

Turf grass Turf grass 0.133 2 0.266 7

Vegetables: Brassica (cole)

leafy CG 5 0.090 3 0.266 7

Vegetables: Bulb SG 3

- 07 0.090 3 0.266 730 Crop/Crop Group ** Crop Group(CG) Or Subgroup (SG) Max Single Rate (lb a.i./A) Max No. of Application s Max Yearly Rate (lb a.i./A) Min Intervals (days)

Vegetables: Cucurbit CG 9 0.090 3 0.266 7

Vegetables: Fruiting & Okra CG 8 & Okra 0.090 3 0.266 7

Vegetables: Leafy except

Brassica CG 4 0.090 3 0.266 7

Vegetables: Root & tuber

/Leaves CG 1 & 2 0.090 3 0.266 7

Watercress Watercress 0.090 3 0.266 7
* from pre

- bloom to mature fruits f or trees and from seeding to harvest for all others ** For detailed crop listing refer to Appendix A

3.2 Exposure Characterization

3.2.1 Environmental Fate and Transpo rt Characterization

3.2.1.1 Physical and chemical properties

The physical and chemical properties of Sulfoxaflor are summarized in Table 5

. The se d ata indicate that the chemical is characterized by a water solubility ranging from 550 to 1,380 ppm
in alkaline to acidic conditions , respectivel y . Sulfoxaflor has a low potential for volatilization from dry and wet surfaces (vapor pressure= 1.9 x 10 - 8 torr and Henry’s Law constant= 1.2 x 10 - 11

atm m 3 mole - 1 , respectively at 25 °C ). Partitioning coefficient of s ulfoxaflor from octanol to water (K ow ) suggests low potential for bioaccumulation in aquatic organisms such as fish. However, the logarithm of its portioning coefficient from octanol to air ( Log K oa =10 ) suggests potential bioaccumulation in terrestrial organisms

, but the expected relative availability in air is low because amount expected to partition into air is low (low volatility) and it’s hal f

- life in the air is expected to be short (range of 8

- 16 hours). Furthermore, sulfoxaflor is not expected to partition into the sediment due to low K oc .

Table 5

. Physical and chemical properties of Sulfoxaflor
Property Description or Value Reference *

CAS Name Sulfoxaflor: cyanamide , N

- [methyloxido[1

- [6

- (trifluoromethyl)

- 3

- pyridinyl]ethyl]

- lambda 4

- sulfanylidene]

-

Registrant Data Molecular Formula C 10 H 10 F 3 N 3 OS
CAS number 946578

- 00

- 3
PC code 005210 Molecular Weight 277.27 g/mo l31 Property Description or Value Reference *

Solubility ( mg/L @ 20 C) Parent X

- 474 pH 5 → 1,380 mg/L 7,270 mg/L pH 7 → 570 mg/L 7,200 mg/L pH 9 → 550 mg/ L 8,480 mg/L In purified water: 670 mg/L 8,090 mg/L 478320

- 10
478320

- 23 for X

- 474

Vapor pressure Parent 20°C → ≤ 1.1 x 10 - 8 torr; ≤ 1.4 x 10 - 6 Pa; ≤ 1.4 x 10 - 11 atm 25°C → ≤ 1.9 x 10 - 8 torr; ≤ 2.5 x 10 - 6 Pa; ≤ 2.5 x 10 - 11 atm
X

- 474
25°C → ≤ 2.0 x 10 - 9 torr; ≤ 2.7 x 10 - 7 Pa; ≤ 2.7 x 10 - 12 atm 478320

- 06
478320

- 22 for X

- 4 74 Henry’s Law Constant (@ 20 &
25 C) 6.7 x 10 - 12 atm m 3 mole - 1 ; 5.1 x 10 - 9 torr m 3 mole - 1

1.2 x 10 - 11 atm m 3 mole - 1 ; 9.1 x 10 - 9 torr m 3 mole - 1 478320

- 07 from VP at 20°C
Calculated from VP at 25°C

Half

- life in Air (t 1⁄2 in hours ) range: 7.8

- 15.5 EPI

- Suit v3.2 (AOPWIN) & Level III Fugacity Model Log K
oa 10.11 EPI

- Suit v3.2 (KOAWIN )

K
ow @ 20 C & pH 7 Parent: 6 (Log K
ow = 0.802 )
X

- 474, X

- 540 and X

- 457: <2 (Log K
ow = 0.3) 478320

- 11
478320

- 20 /24/27
K
oc 7

– 74 mL/g

3.2.1.2 Fate and Transport Prope rties

The fate and transport behaviour of Sulfoxaflor ha d been investigated in a series of laboratory

and field studies. The submitted laboratory studies were all conducted with 14 C

- labelled active
substance in the pyridine ring as shown in Figure 6

.



### N * 

### S N O N F 3 

### C

* denotes position of radiolabel in the pyridine ring

14 C

- Sulfoxaflor (or XDE

- 2208)
Figure 6

. R adiolabel ed s ulfoxaflor used in fate and transport studies

Sulfoxaflor consist s of two diastereomers in a ratio of approximately 50:50. Each of the diastereomers consists of two enantiomers that cannot be resolved using conventional (non

chiral) high pressure liquid chromatography ( HPLC ) columns

.32 a) Abiotic Degradation
Results indicate that hydrolysis, and both aqueous and soil photolysis are not expected to be important in sulfoxaflor dissipation in the natural environment. The fate properties of sulfoxaflor parent and major degradate X

- 474 in abiotic systems are summarized in Table 6

. In a hydrolysis study, the parent was shown to be st able in acidic/neutral/alkaline sterilized aqueous buffered solutions (pH values of 5 , 7 and 9; MRID 47832

- 149 ). In addition, p arent chemical as well as its major degradate , were shown to degrade relatively slowly by aqueous photolysis in sterile and natural pond water (t1⁄2= 261 to >1,000 days; MRID 478322

- 83/84 ). Furthermore, sulfoxaflor
was stable to photolysis on s oil surfaces ( MRID 478 320

- 21 ).

Table 6

. Fate properties of sulfoxaflor parent and its major degradate X

- 474 in abiotic systems

Property Description or Value & Other Rel e vant Information Reference (MRID)

Hydrolysis half

- life
@ 2 5 °C Parent:

Stable i n sterile a queous buffered solution at pH values of 5, 7
and 9

478321

- 49 X 4 74 degradate ( n o study; results inferred from the dark controls of the aqueous photolysis study (MRID 478322

- 83): Stable in sterile a queous buffered soluti on at pH7

Environmentally relevant Aqueous photolysis half

- lives
@ 25 °C; 40° N
latitude in summer sunlight Parent: >1,000 days in sterile aqueous buffered solution at pH 7.0

637 days in natural pond water, Italy; buffered at pH 8.2 Major degradates : None Minor degradates: X

- 0 61 [1

- [6

- (trifluoromethyl)(2

- 14C)pyridin

- 3

- yl]ethanol] with a maximum of 2.5% @ study termination (day 14)

(Note: Transformation products was not tracked for the natural pond water samples, transformation products data
above a re for sterile /buffered water only)

X

- 474 degradate: 261 days in sterile aqueous buffered solution at pH 7 >1,000 days in natural pond water, Italy; buffered at pH 8.2 Major degradates: None Minor degradate: X

- 061 (maximum 4.4% at study termination) and X

- 922 [1

- (6

- trifluoromethyl

- pyridine

- 3

- yl) ethanone] with a maximum of 8.6% at study termination (day 14) Sterile Water Study: 478322

- 83

Natural water study: 478322

- 84

Soil photolysis half

life Stable 478320

- 2133 b) Biotic Degradation

The fate properties of s ulfoxaflor and its major degradation product X

- 474, in biotic systems

, are summarized in Table 7

. In addition, Table 8 contains a summary for the degradation product s observed following parent degradation in various systems. Expected environmental degradation pathways and transformation profiles for Sulfoxaflor are also presented in Figure 7

.

Based on these data, sulfoxaflor is expected to bio degrade rapidly in aerobic soil (half

- lives <1 day) . Under aerobic aquatic conditions, biodegradation proceeded at a more moderate rate with
half

- lives ranging from 37 to 88 days. The major degrade formed in aerobic soil/aquatic system s is X

- 474

. Under anaerobic soil conditions, the parent compound was metabolized with half

- lives of 113 to 120 days while u nder anaerobic aquatic conditions the chemical was more persistent
with half

- lives of 103 to 382 days.

In contrast to its short

- liv ed parent, the major degradate X

- 474 is expected to be more persistent
than its parent in aerobic/anaerobic aquatic systems and some aerobic soils. In other soils, less persistence is expected due to mineralization to CO 2 or the formation of other minor de gradates

.

Table 7

. Fate properties of sulfoxaflor parent and major degradate X

- 474 in biotic systems

Property Soil or Water/Sediment System* Half

- life & (Fitting Equation) Reference (MRID) Parent t1⁄2 X

- 464 t1⁄2

Aerobic Soil Met abolism (days):
2 5 °C/ 75% of the water holding capacity ( WHC ) Lenawee light clay, Michigan, USA: CL 0.3 >1000

478655

- 78 Pullman light clay, Texas, USA: CL 0.4 >1000 Fayette clay loam

, Iowa, USA: L 0.6 >1000 Slagle clay loam

, Virginia, USA: SL 0.5 >1000

Aerobic Soil Metaboli sm (days): EU
Soils incubated for 4 months at 2 0 °C/ 40% of the WHC Cranwell Series (Site I), Lincolnshire, UK: LS <0.1 203

478320

- 13 Aberford Series (Site J1), Rutland, UK : L <0.1 85
Malham Series (Site E)

, Derbyshire, UK: SL <0.1 381

LUFA 5M

, Kreis Rheim

- Pfalz, Germany: SL <0.3 251

Aerobic Soil Metabolism (days) Aberford Series (Site J1), Rutland, UK : L ; EU
Soil incubated for 4 months at 1 0 °C/40% WHC <1 184 478320

- 13

Aerobic Soil Metabolism (days): Aberford S eries (Site J1), Rutland, UK : L ; EU Soil sterilized/incubated for 4 months at 2 0 °C/
40% of the WHC <1 NC 478320

- 13

Soil Metabolism: Aerobic Phase (days) CL Soil, Texas: 8 hrs under aerobic conditions
then 113 d under anaerobic conditions @
2 5 °C/35% of the WHC NC NC

478322

- 79 Anaerobic phase (days) NC 320

Soil Metabolism: Aerobic Phase (days) Aberford Series (Site J1), Rutland, UK : L; 2 hrs
under aerobic conditions & 120 d under a naerobic
conditions @ 25 °C/40% of the WHC NC NC

478320

- 13 Anaerobic phase (days) NC 532

Aerobic Aquatic Metabolism (days for the total system): Pond water/sediment system, Derbyshire, UK ( system

- 1 ) * Water: pH 6.7 and dissolved organic carbon 6.2 ppm) and Sediment: sand (pH 6.3 and organic carbon 0.6%) incubated for 103 d @ 2 0 °C 88 NC 478320

- 1434 Property Soil or Water/Sediment System* Half

- life & (Fitting Equation) Reference (MRID) Parent t1⁄2 X

- 464 t1⁄2

Aerobic Aquatic Metabolism (days for the total system): Pond water/sediment system, Staffordshire, UK ( system

- 2 ) * Water: pH 7.8 and dissolved organic carbon 6.5 ppm) and Sediment: silt loam (pH 7.8 and organic carbon 3.9%) incu bated for 10 3 d @ 20 °C 37 NC

Anaerobic Aquatic Metabolism (days for the total system): Pond water/ sediment system, VA ( system

- 3 ) * Water: pH 7.5 and dissolved organic carbon 10.0 ppm) and Sediment: sand (pH 4.9 and organic
carbon 0.2% incubated for 100 d @ 25 °C 382 5,270

473723

- 11 Anaerobic Aquatic Metabolism (days for the total system): Pond water/ sediment system, IA ( system

- 4 ) * Water: pH 7.8 and dissolved organic carbon 6.7 ppm) and Sediment: sandy clay loam (pH 7.3 and organic carbon 1.4%) incubate d for 100 d @ 25 °C 103 1,090

* Abbreviations: NC = Cannot be calculated due to gain or only few points is available; Soil Textural Classes: CL = Clay Loam; L = Loam Soil; SL = Sandy Loam Soil; and LS = Loamy sand ; Data for aerobic systems from parent study w hile that for anaerobic systems from two separate studies: one for parent and the other for the major degradate X

- 474

Table 8

. Parent degradation products for systems described in Table 7 , above

Property Soil or Water/Sediment Sys tem Parent Degradation Products (% of Applied) Reference (MRID)

Aerobic Soil
Metabolism
US soils @
2 5 °C/ 75%
of the WHC Lenawee light clay, MI Major (MAJ): X

- 474 (max. 98 to 99% by 14 to 31 days then decreased to

83

- 90% @ termination); Minor (MIN): Non e; Mineralization (MRL):

CO 2 (max. 1

- 3% @ termination); Non

- extractable residues (NER): max.
7

- 13% @ termination 478655

- 78 Pullman light clay, TX
Fayette clay loam

, IA

Slagle clay loam

, VA

Aerobic Soil
Metabolism

EU Soils @
2 0 °C/ 40%
of the W HC Cranwell Series, UK MAJ: X

- 474 (max. 100 % by day 1then decreased to 35

- 79% @

termination ), and X115795

- 40 (from 0 to 12%, formation time was variable “ranged from 4 to 81 days after incubation” with no clear decline; Data suggest net gain @ termination ) ; MIN: X115794

- 57 (from 0 to 9%, formation time was variable “ranged from 3 to 32 days after incubation” with no clear decline; Data suggest net gain @ termination ); MRL : CO 2 (max. 5

- 9% @ termination in all soils except Aberford Series with a max. of

28 to 32% ); NER: max. 4

- 8% @ termination 478320

- 13 Aberford Series, UK
Malham Series, UK

LUFA 5M

, Germany

Aerobic Soil
Metabolism Aberford Series (Site J1),
UK @ 1 0 °C/ 40% of the
WHC MAJ: X

- 474 (max. 97 % within one day then declined to 68% @

termi nation) ; MIN: X115794

- 57 (Max. 8% in 62 days decreasing to only 7% within the period from day 90 to termination); and X115795

- 40 (Max. 8% within the period from 62

- 90 days decreasing to only 7% @ termination);

MRL : CO 2 (max. 6% @ termination; NER: max. 9% @ termination 478320

- 13

Aerobic Soil
Metabolism Aberford Series (Site J1),
UK sterilized then
incubated @ 2 0 °C/ 40% of
the WHC MAJ: X

- 474 (max. 83 % after 90 days then declined to 77% @ termination) ;
MIN: None; MRL : CO 2 (max. <1% @ termination) ; NER: max . 6% @

termination 478320

- 13

Aerobic/
Anaerobic
Soil Clay Loam Soil, TX : Aerobic/Anaerobic
Phases MAJ: X117194

- 74 (max. 95 % after 20 days then declined to 75% @ termination); MIN: None; MRL : CO 2 (max. 0.45% @ termination) ; NER:

max. 25% @ termi nation 478322

- 7935 N S N O F 3 C N H 2
O

N S N H O F 3 C N S O O F 3 C Property Soil or Water/Sediment Sys tem Parent Degradation Products (% of Applied) Reference (MRID)

Metabolism Aberford Series (Site J1),
UK: Aerobic/Anaerobic
Phases MAJ: X117194

- 74 (max. 97 to 98 % after 4 to 7 days then declined to 84%

@ termination ); MIN: None; MRL : CO 2 (max. 0.1% @ termination ); NER:

max. 12% @ termination 478320

- 13

Aerobic Aquatic
Metabolism System 1: Pond water/ sediment system , UK MAJ: X117194

- 74( max. ranging from 25 to 71% in system

- 1 and 47 to 66% in system

- 2 occurring at 61

- 103 days with no apparent decline ) ; MRL : CO 2 :

max. 0.6 to1.5%, in systems 1 and 2, respectivel y, at study termination ;
MIN: max. 6 to 26% in systems 1 and 2, respectively @ termination 478320

- 14 System 2: Pond water/ sediment system , UK

Anaerobic Aquatic
Metabolism System 3: Pond water/ sediment system, VA MAJ: Non e; MIN: X

- 474 (max. 3% @ 14d ays in systems

- 3 and max. 8% @ study termination in system

- 4 (other replicate was only 3%) ; MRL : CO 2 :
<1% in systems

- 3 and 4 @ termination ; NER: max.12 to 37% in systems

- 3 and 4, respectively @ termination 473723

- 11 System 4: Pond water/ sediment system, IA

* Half

- lives were >1,000 days in US soils with no degradates observed. In contrast, half

- lives ranged from 85

- 381 days in EU soils producing degradate X

- 540 & X

- 457. Separate aerobic soil experiments showed that bot h of these degradates are persistent (90 th percentile half

- lives were 526 days (range 96 to 670 days) for X

- 4 57 and 2,808 days (range 71 to 3,630 days) for X

- 540 Rapid Bio

- degradation (90 th percentile t1⁄2= 0.4 days) (Aerobic Soil System)

Slow Aqueous Photolysis (t 1/2 = 261 days) Very Slow Aqueous Photolysis (Practically Stable ) Sulfoxaflor
Parent

X117210

- 61 (X

- 061)

X117189

- 22 X

- 474

X

- 457 X

- 540 Very Slow Biodegradation*

(90 th percentile t1⁄2= 825 days) (Aerobic Soil System)36 Figure 7 . Expected environmental degradation pathways and transform ation profiles for
Sulfoxaflor

More details on laboratory biotic metabolism studies are included in Appendix A . Additionally,
Table 9 contains information about degradates of sulfoxaflor identified in varied bioti c and biotic systems.

Table 9 . Selected environmental d egradates of sulfoxaflor

Characteristics Transformation Product Structure

Common Name X11719474 (X

- 474)

IUPAC N

- (methyl(oxido){1

- [6

- (trifluoromethyl) pyridin

- 3

- yl]ethyl}

- λ4

- sulfanylidene) urea

SMILES Code c1c(ncc(c1)C(C)S(=NC(=O)N)(C)=O)C(F)(F)F
Molecular Weight 297 g mole - 1

Molecular
Formula C 10 H 12 F 3 N 3 O 2 S

Common Name X11579457 (X

- 457)

IUPAC [ 5

- [1

- (S

- methylsulfonimidoyl)ethyl]

- 2

- (trifluoromethyl)pyridine

SMILES Code c1c(ncc(c1)C(C)S(=N)(C)=O)C(F)(F)F
Molecular Weight 252.25 g/mole

Molecular
Formula C 9 H 14 F 3 N 2 OS

Common Name X11519540 (X

- 540)

IUPAC 5

- (1

- methanesulfonyl

- ethyl)

- 2

- trifluoromethyl

pyridine

SMILES Code c1c(ncc(c1)C(C)S(=O)(=O)C)C(F)(F)F

Mole cular Weight 253.24 g/mole

Molecular
Formula C 9 H 10 F 3 NSO 2

Common Name X11721061 (X

- 061)

IUPAC (1

- [6

- (trifluoromethyl)(2

- 14C)pyridin

- 3

- yl]ethanol)

SMILES Code C1=CC(=NC=C1C(C)O)C(F)(F)F

Molecular Weight 191.15

Molecular
Formula C 8 H 8 F 3 NO

Common Name X11718922

IUPAC 1

- (6

- trifluoromethyl

- pyridine

- 3

- yl) ethanone

SMILES Code C1=CC(=NC=C1C(C)=O)C(F)(F)F

Molecular Weight 189.14

Molecular
Formula C 8 H 6 F 3 NO

c) Field D issipation in T errestrial S ystems N S N O F 3 C N H 2
O

N S N H O F 3 C

N S O O F 3 C

N F 3 C O H

N F 3 C O37 Extensive data were collected from the terres trial field dissipation (TFD) studies for sulfoxaflor (MRID 47832282 ). Complete analysis of the data is included in Appendix A and hereu nder is a summary of these data. The terrestrial field dissipation (TFD) study for s ulfoxaflor was designed based on the results of laboratory studies. These studies showed that sulfoxaflor degraded rapidly in soil, forming a major degradation product (X

- 474), and two minor degradation products (X

540 and X

- 457). Adsorption/desorpti on studies indicated that both parent sulfoxaflor and major/minor degradate (X

- 474, X

- 540 and X

- 457) are expected to be mobile. Additionally, sulfoxaflor and it degradate X

- 474 are systemic and were found to be stable to hydrolysis at pH 5, 7, or 9. Theref ore, the TFD study design included leaching and plant uptake modules. Due to the low vapor pressure and Henry’s law constant of sulfoxaflor, volatility in the field was not
measured.

Five sites were selected for conducting bare and cropped

- plots in Califor nia (CA), Florida (FL), North Dakota (ND), Ontario, Canada (ON), and Texas (TX). Sulfoxaflor soluble concentrate
formulation ( 242 g active ingredient per litre of product or 22% w/w) was surface applied one to
three times at nominal single rate s ranging fr om 100 g a.i./ha (equivalent to 0. 089 lb a.i/A) to 200 g a.i./h a. The study design consisted of two treated plots (one cropped and one bare soil) and an untreated control plot at each study location (located at least 30 m from the treated plot). Treated
and rotational crops representative of the geographical location of each test site were planted on areas designated for cropped plots over the course of the study. The California and Florida test sites were equipped with soil

- suction lysimeters for the collec tion of soil

- pore water samples. As required, supplemental irrigation (method not reported) was supplied to maintain at least 110% of long term average rainfall. The monthly target moisture input was set at 400% of the local historical average monthly prec ipitation in California and 120% in other sites. Other normal agronomic practices were followed.

Soil core samples were collected, for all sites, immediately after the first application to a depth of 6”. Additionally, soil samples were collected from the s oil profile to a depth of 36 ” at various sampling dates up to and including the end of the study (18 months in California, 15 months at other sites). The soil samples were extracted with 90:10 acetonitrile: 1.0 N hydrochloric acid (v: v) on a flat

- bed shak er and extracts were concentrated prior to analysis. Soil pore

- water samples were collected at depths of 3, 6, and 8 ft. in FL or 9 ft. in California at 1, 6, 13, 28 days and 2, 4, 6, 9, 12 and 15 months after the first treatment. Water samples were analy zed directly. Soil and water samples were analyzed for sulfoxaflor and its aerobic soil metabolite (X

- 474, X

- 54 0 and
X

- 457 ) using HPLC) with positive

- ion electrospray (ESI) tandem mass spectrometry (HPLC/MS/MS).

For at least one sampling event at each site , a set of transit stability samples were prepared to evaluate the stability of sulfoxaflor and its transformation products during shipment and storage. Soil samples were spiked at 1x and 100x the limit of quantification ( LOQ= 0.001 ppm ) . Pore water sample s were spiked at 1x and 40x the LOQ ( 0.05 ng/mL )

. Spiked sample s were subjected to the same procedures as the field samples. Average recovery in transit stability soil samples ranged between 82 and 97% for sulfoxaflor, 94 and 125% for X

- 474 , 77 and 101% fo r X

- 457

, and 81.0 and 111% for X

- 540 . Recovery in transit stability pore water samples was 88 % for38 Sulfoxaflor, 95 and 88% for X

- 474 , 85 and 84% for X

- 540 , and 99 and 93% for X

- 457 , in California and Florida, respectively.

Crop samples were collected at v arious crop growth stages during the first and second growing seasons and analyzed for sulfoxaflor, X474 ( i.e ., the major soil metabolite)and X061 ( i.e ., the plant metabolite) using a reverse

- phase polymeric solid

- phase extraction ( SPE ) cartridge on

- line system using HPLC/MS/MS. The Method of Analysis l imits of Detection/Quantification L OD / LOQ and Performance were reported and were within acceptable limits. In addition application was verified by tank mix data, Soil deposition trays/saturated pads and zer o

- time concentrations.

A summary of the TFD Half

- lives for p arent Sulfoxaflor is included in Table 10

.

Table 10

. Field dissipation half

- lives (DT50 in days) for sulfoxaflor from the top 6” of the soil and the entire soil profile (0

- 36”)

Chemical Considered Depth CALIFORNI A * FLORIDA* NORTH DAKOTA* ONTARIO* TEXAS*

Bare Cropd Bare Cropd Bare Cropd Bare Cropd Bare Cropd

Sulfoxaflor
Parent 0

- 6” (top soil) 2.0 1. 9 0. 7 1.6 0.3 0.1 0.6 0.9 8. 1 1.5

0

- 36” (entire profile) ND ND ND ND ND 0. 2 0. 6 ND 8.1 1.5

Bare = Bare soil plots; cropd = cropped plots; ND = Not determined due to lack of data

Field leaching was also tested using soil pore water suction lysimeters to collect soil

- pore water samples in two of terrestrial field dissipation studies: CA and FL. soil

- suction lysimeters were installed at sampling depths of 3, 6, and 8 (FL) or 9 (CA) feet below ground surface. Soil

- pore water samples were collected at

- 1, 6, 13, 28 days and 2, 4, 6, 9, 12 and 15 months after the first treatment. Although sulfoxaflor was not detected in pore water at any time/depth sampled in the high leaching profile in CA, it was concluded that non

- detection was related to time of sampling rather than absence of leaching ( i.e., samples missed the leaching events).

Consistent with laboratory studies, major degradate X

- 474 was the major transformation product in the field dissipation studies

. Data for the top 6” of the soil indicate the rapid formation of X

474 as its conce ntration of 13

- 54% of the applied parent was observed immediately following the first application. This was the case also following the second and third applications in CA and
FL sites. Furthermore, data suggest that X

- 474 has the potential to carryover es pecially if leaching is lim i ted ( concentrations ranging from 1 to 18% of the applied parent were left in the soil after a year)

. D issipation half

- lives (DT 50 ) for X474 were calculated for residues in the top
6” of the soil and the whole 0

- 36” soil profile following the same procedure described for above for parent . Results are summarized in Table 11

.39 Table 11

. Field dissipation half

- lives (DT50) for major degradate X

- 474 from the top 6” of

t he soil and the entire soil profile (0

- 36”)

Chemical Considered Depth CALIFORNIA* FLORIDA* NORTH DAKOTA* ONTARIO* TEXAS*
Bare Cropd Bare Cropd Bare Cropd Bare Cropd Bare Cropd

X

- 474 Degradate 0

- 6” (top soil) 27 52 4 9 62 217 40 248 109 51 58
0

- 36” (e ntire profile) 6 10 49 60 200 36 114 5 9 45 5 2

Bare = Bare soil plots; cropd = cropped plots; ND = Not determined due to lack of data

D ata summarized in Table 11 indicate that X

- 474 is much more persistent than its parent. Dissipation half

- lives ranged from 49 to 248 days and from40 to 109 days in bare soil and cropped plots, respectively. Additionally, X

- 474 leached below the top 6” soil layers at all terrestrial field dissipation sites reaching 36, 30, 24, and 18” below the surface. At CA and FL sites, residues of X474 reached a depth of 36” with maximum concentrations of 19.5 to 20.6 ppb (≈19

- 20% of the applied parent) at 28 days after the 1 st application in CA and maximum concentrations of 1.7 to 2.5 ppb (≈2

- 4% of the applied parent) at 2

- 15 months after the 1 st application in FL. In ND, X

- 474 reached a depth of 30” with maximum concentrations of 1.0 to 2.3 ppb (≈2

- 4% of the applied parent) at 2

- 11 months after the 1 st application. At ON (Canada) site, it reache d a depth of 18” with maximum concentrations of 0.5

- 1.6 ppb (≈0.6

- 10% of the applied parent) at 9 months after the 1 st application. At TX site, it reached a depth of 12” below the soil surface with maximum concentrations of 14.7 to 17.5 ppb (≈18

- 22% of the applied parent) at 4

- 9 months after the 1 st application. Observed data confirm that field dissipation of X

474 , from the top soil, is mainly related to transport (K oc = 7 to 74 mL/g) rather than degradation.

Other Degradates: X

- 540 and X

- 4 57 were minor tr ansformation product s in the field. In most field sites, the two degradate s dissipated from the 0

- 6 inch soil la yer before the end of the study. The observed formation of minor quantities of degradates X

- 457 and X

- 540 is probably related
to the relative hi gh persistence of its m ost probable parent (the major d egradate X

- 474 ). A kinetic analysis was not performed for X

- 5 40 and X

- 4 57.

Crop residue results for all five test sites were monitored for parent sulfoxaflor and its major

t ransformation product X

- 47 4 , as well as X

- 061 (a plant metabolite). Field plant data can be used
to characterize foliage interception /uptake of applied parent and nature /concentration of residues in target and rotational crops. Other data were collected on nature and concentration o f residues in target and rotational crops and summary /analysis of this data are included in Appendix A

.

T op soil carryover is not expected for sulfoxaflor parent but is expected for X

- 474, X

- 457 and X

540. Estimate d carryover for all of the three degradates were minimal (0

- <1%) for CA site while it was significantly higher for FL, ND, ON and TX sites. For X

- 474

, the maximum top soil carryover is estimated to be 15% for FL, 39% for ND, 40% for ON and 46 % for TX. This is a reflection of the high formation/persistence of the degradate X

- 474. For X

- 540, the maximum top soil carryover is estimated to be 1% for FL, 4% for ND, 3% for ON and 5% for TX. For X

457, the maximum top soil carryover is estimated to be <2% in FL, N D, ON and TX

.40 d) Mobility

Laboratory adsorption data for sulfoxaflor indicate that the chemical can be characterized by very high to high mobility based on Freundlich organic carbon

- based adsorption (K foc ranged
from 11

- 72 mL g - 1 with an average of 35 mL g - 1 and a median value of 31 mL g - 1 ). However, rapid degradation in soil is expected to limit the amounts of the chemical that may potentially leach and contaminate ground water. Contamination of groundwater by sulfoxaflor will only be expected when excessive rain occurs within a short period (few days) of multiple applications in vulnerable sandy soils.

Adsorption/desorption properties of parent sulfoxaflor and three of sulfoxaflor degradates were examined in seventeen soils for parent and X

- 474, seven soils f or X

- 457 and six soils for X

- 540. Results for the adsorption phase are summarized in Table 12 along with soils characteristics and
locations.

Table 12

. Transport properties Sulfoxaflor and i ts degradates

Soil: Geographic Location K foc For Parent & Degradates L/Kg 1 T; S; Si & C= Texture; Sand; Silt & Clay 2
pH %
OC CEC Parent X

- 74 X

- 57 X

- 40 T S% Si% C%

Lenawee: MI, USA 31 24 44 20 CL 31 35 34 5.9 1.8 16.9
Pullman

- 1: TX, USA 47 40 23 24 CL 31 34 35 6.9 1.2 23.2 Fayette: Iowa, USA 50 50 26 25 L 34 47 19 6.3 1.1 14.3 Slagle: VA, USA 34 21 35 ND SL 54 30 16 6.4 1.0 5.0
M773: CA, USA 55 76 ND ND S 86 13 1 6.3 0.3 3.2
M774: FL, USA 53 31 ND ND LS 86 8 6 6.2 0.8 4.3
Bearden

- Lindaas: ND, U SA 72 68 ND ND C 17 32 51 7.9 1.8 36.0
Pullman

- 2: TX, USA 46 45 ND ND CL 27 38 35 6.7 1.1 21.5
Lacustrine: ON, Canada 29 23 ND ND L 31 46 23 6.9 1.8 8.9 Cranwell, Site I: Lincolnshire, UK 21 13 11 1 LS 81 16 3 7.6 1.3 9.2 Aberford, Site J1: Rutland, UK 12 7 2 6 L 49 32 19 7.3 6.7 37.9 Malham, Site E: Derbyshire, UK 11 8 10 6 SiL 28 59 13 6.2 3.5 20.3
LUFA 5M: Kreis Rheim

- Pfalz, Germany 24 19 ND ND SL 61 26 13 7.4 1.2 6.3
M775: Bologna, Italy 31 32 ND ND SCL 54 23 23 7.4 1.3 13.2
M776: Valencia, Spai n 30 22 ND ND CL 42 30 28 7.8 1.2 9.8
M780: Haine

- Et

- Loire, France 20 14 ND ND CL 43 24 33 7.8 1.7 15.6
M781: Lower Saxony, Germany 23 18 ND ND SL 19 62 19 6.3 1.1 10.0 Average Values 35 30 22 14
Median Values 31 23 23 13

1 Degradates: X

- 74 = X11719474; X

- 57 = X11579457; X

- 40 = X11519540; ND= Not determined

2 CL= Clay Loam; L= Loam; SL= Sandy Loam; S= Sand; LS= Loamy Sand; C= Clay; SiL= Silt Loam; SCL= Sandy Clay
loam

Data for Freundlich organic carbon based adsorption (K foc ; Table 12 ) indicates that parent sulfoxaflor and it degradates are expected to be highly mobile to mobile in soil systems (FAO,41 2000) 5

. One desorption cycle was carried out for parent sulfox aflor and transformation products were not subjected to the desorption step. Freundlich desorption isotherms ( K f ) ranged from 0.18 to 0.89 (K foc of 9

- 61 suggesting that parent sulfoxaflor will not bind irreversibly and that some
material will desorb from t he soil.

e) Environmental Chemistry Methods and Independent Laboratory
Validation

Table 13 contains a summary of the analytical methods to be used for determining concentrations of parent sulfoxaflor and degradates in soil, water, and air. The limit of quantification established for each method/analyte is also included in the same Table.

Table 13

. Summary of analytical methods (residue) for soil, water and air (method type for all analytes= LC/MS/MS)

Method ID LOQ (For All Analytes) Reference MRID

Soil (Analytes: Sulfoxaflor, X11519540 (X

- 540), X11579457 (X

- 457) and X11719474 (X

- 474)

(1) Dow AgroSciences Study Number 091185 0.001 mg/kg 47832269

(2) Dow AgroSciences Study Number 101100 0.00 1 mg/kg 47832256

(3) Pyxant Labs Inc. Study Number 081078

- 1906A 0.001 mg/kg 47832270

Water (Analytes: Sulfoxaflor, X11519540 (X

- 540), X11579457 (X

- 457) and X11719474 (X

- 474)

(1) Dow AgroSciences Study Number 091186 0.05 μg/L (with SPE); 0.25 μg/L (with out SPE) 47832268

(2) Dow AgroSciences Study Number 101650 0.05 μg/L (with SPE) 47832267

(3) Pyxant Labs Inc. Study Number 081078

- 1906B 0.05 μg/mL 47832266

Air

Not reviewed; not required for registration in the United States; Not expected to partition into the air. 47832265

The soil method is applicable for the quantitative determination of residues of Sulfoxaflor and its metabolites (X

- 540, X

- 457, and X

- 474) in soil (MRID 47832269). Validation was conducted using four soil types; the soil textural c lassifications were silt loam, sandy loam, clay loam, and loam. The method was validated over a concentration range of 0.001

- 1.0 mg/kg with a validated limit of quantitation of 0.001 mg/kg and limit of detection of 0.0003 mg/kg (MRIDs 37832256
and 4783227 0). The mean recovery for fortified control samples was within the acceptance

5 Food and Agriculture Organization of the United Nations (FAO), 2000. FAO pesticide disposalseries 8. Assessing soil contamination: A reference Manual. Appendix 2. Parameters of pesticides that influence processes in the soil. Editorial Group, FAO In formation Division, Rome.42 range of 70

- 110% with a relative standard deviation (RSD) of < 20% with one exception. The average recovery for X

- 540 at the 0.010

- mg/kg level was 113%; however, the data was

co nsidered valid as RSD was less than 6% for 29 replicates. The water method is applicable for the quantitative determination of residues of sulfoxaflor and its metabolites (X

- 457, X

- 540, and X

- 474) in drinking water (tap water), ground water (well water), a nd surface water (pond water) (MRID 47832268). The method was executed with and
without a solution purification step using an online reverse

- phase polymeric solid

- phase extraction (SPE) cartridge. T he method was validated over a concentration range of
0.0 50

- 50.0 μg/L (MRID 47832267) with a validated limit of quantitation was:

• 0.050 μg/L when the SPE step is included; and

• 0.250 μg/L when the SPE is not included The mean recovery for fortified control samples was within the acceptance range of 70

- 110%
with a relative standard deviation (RSD) of < 20%. For ground water (pore water), the method is applicable for the quantitative determination of residues of sulfoxaflor, and its major metabolites (X

- 457, X

- 540, and X

- 474) in ground water (soil pore). The metho d was validated over a concentration range of 0.050

- 2.00 μg/L with a validated limit of quantitation of 0.050 μg/L (MRID 47832266).

f) M etabolism, Distribution and E xpress ion of Residues in P lants

Sulfoxaflor is a systemic pesticide; therefore it is import ant to analyze available plant data
toward understanding how exposure pathways may be affected by plant s

. A study was conducted, on tomato plants, where 14 C sulfoxaflor was foliar ly applied in one e xperiment and was soil applied in another 6

. In the foliar application experiment, the chemical was applied four times/directly into foliage at a seasonal total of 600 g a.i/ha. In the soil application experiment,

14 C

- sulfoxaflor was applied twice/directly into the soil at a seasonal total rate of 400 g a.i/ha. A summary of the data for both experiments are included in Figure 8

.

6 Rotondaro , S. L., Balcer, J. L., and Smith, K. P. A Nature of the Residue Study with 14C

- SULFOXAFLOR Applied to Tomatoes

, Unpublished report of Dow AgroSciences, study ID 070021, 22 February 2010, amended 24
March 2010.43 Figure 8 . Distribution of sulfoxaflor residues in tomato following foliar and soil applications

As shown in Figure 8 , the majority of the radioactive residue in the foliar

- applied tomato plants was identified as parent followed by two degradates: X117194

- 74 and X117210

- 61. Plant metabolism appears to produce the two de gradates in parallel from parent and in sequence from parent to X

- 474 to X

- 0 61. It is noted that reported aerobic soil metabolism data (elsewhere in this document) show that degradate X

- 474 is the major aerobic soil degradate of sulfoxaflor
while X

- 0 61 is not a product of this route of degradation. In this foliar experiment, the only Foliar-IM AFA Foliar-IM-ASA Foliar-M-ALA Soil-IM-AFA Soil-M-ALA 0% 5% 10% 15% 20% 25% 30% Parent X11719474 X11721061

Foliar-1 DAL Foliar-7 DAL Foliar-14 DAL Soil- 14 DAL Soil- 21 DAL Soil- 28 DAL 0% 10% 20% 30% 40% 50% 60% 70% 80% Parent X11719474 X11721061

Foliar/Soil = foliar “solid columns”/soil application “hatched columns”; IM/M = immature/mature plants ; AFA/ASA/ALA = after 1 st /2 nd /Last Application; DAL = days after last application
Chemical source: Foliar= from Foliar applied parent; Soil= from Soil applied parent Residue s in plants

Residues in fruits % of Applied

% of Applied

Not Shown:
<1% of

- 40

plus

- 57 Degradates44 source of sulfoxaflor is foliage as it was not applied to soil. Presence of sulfoxaflor and degradates X117194

- 74 and X117210

- 61 in the plant, suggest that parent sulfoxaflor e ntered the plant from foliage and was subjected to plant metabolism producing degradates X

- 474 and X

061 . Therefore, both of these degradates can be considered as plant metabolism degradates.

In contrast to folia ge , the majority of the radioactive residue s in the tomatoes proper w ere identified as the degradate X

- 474 followed by s ubstantially low er concentrations of parent and
X

- 0 61 ( Figure 8 ). The noticeable increase of X

- 474 in tomato foliage suggests the presenc e of
an additional source for X

- 474 ( e.g ., root uptake from soil). It appears that sulfoxaflor parent was subjected to three parallel processes: movement into plant as parent (source of parent in the plant), degradation in the soil producing X

- 474 that als o appear to move into the plant via root uptake , plant metabolism (reduc ing parent concentration entering the plant with production of
additional amounts of X

- 474 in addition to X

- 061 ). In the plant, the combined results of these three processes are high X

- 4 74 concentration (movement from soil plus production in plant) and
low concentration of. These residue studies suggest that similar to the parent, X

- 474 is systemic
and that it can be produced by soil and plant metabolism.

Equivalent metabolism studies were executed for succulent peas 7

, three foliar applications, a total of 601 g a.i./ha; and two soil applications, total ing 434 g a.i./ha), lettuce (MRID ? 8 , three foliar, one on immature plants and two on mature plants, total ing 599 g a.i./ha along w i th one soil application at a rate of 454 g a.i./ha ) and rice 9 , three foliar application, total ing 578 g a.i./ha along with one soil application at a rate of 474 g a.i./ha). Maximum observed concentrations for
sulfoxaflor parent and degradates are summarized in Figure 9 for all studies including tomatoes.

7 Hast ings, M. J., Rotondaro, S. L., and Balcer, J. L. A Nature of the Residue Study with [14C]

- XR

- 208 Applied to

Peas

, Unpublished report of Dow AgroSciences, study ID 070035, 13 May 2010.

8 Graper, L. K., Balcer, J. L., and Smith, K. P. A Nature of the Resi due Study with [14C]

- XDE

- 208 Applied to
Lettuce

, Unpublished report of Dow AgroSciences, study ID 070033, 01 June 2010.

9 Rotondaro, S. L., Balcer, J. L., and Smith, K. P. A Nature of the Residue Study with 14C

- XDE

- 208 Applied to
Rice

, Unpublished report of Dow AgroSciences, study ID 070034, 23 December 2009, amended 13 January 2010
and 24 March 2010.45 

### 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

Parent X11719474 X11721061

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%Immature Lettuce &TomatoImmature Tomato &PeasImmture RiceMature LettuceMature Tomato & RiceMature PeasTomato Fruits & RiceGrainPeas Pods

Figure 9

. Distribution of maximums of sulfoxaflor residues in four crops following foliar and soil applications

Data depicted in Figure 9 indicate that when sulfoxaflor is applied to foliage it enters immature plants giving varied maximum concentrations (rice> tomatoes& peas> lettuce). In contrast, on ly limited sulfoxaflor parent enters the plant before it degrade s into X

- 474 which appears to be
what enters the plants giving relatively high concentrations (over 60% with tomato, lettuce & peas> rice). The level of “soil originate d parent sulfoxaflor” th at enters the plant is relatively low due to the fact that parent is not expected to be available in the soil system due to its rapid degradation. As plants mature, tissues appear to retain “foliage originated parent sulfoxaflor” at Foliar Application Soil Application

% of Applied46 the same level in peas, lower level in rice and at higher level in tomato. In fruits, grain and pods, the level of “foliar originated parent sulfoxaflor” is maintained with concentration ranging from 30 to 60%. “Soil originated X

- 474” appear to show similar patterns to its paren t with relatively higher concentrations. Plant metabolism of foliage or soil originated parent and degradate X

- 4 74 appears to be occurring at all stages of plant development producing X

- 061 and other degradates. The pattern of formation and decline for par ent and degradate is difficult to deduce due to the apparent occurrence of multiple processes including degradation and translocation; within the plant and from soil/foliage to plant.

When s ulfoxaflor is applied foliarly on growing crops it is intercepted by the crop canopy . Data presented above appear to indicate that sulfoxaflor enters the plant and is incorporate d in the plant foliage with only limited degradation. It appears that this is the main source of the
insecticide sulfoxaflor that would kil l sa p sucking insects . This is because washed

- off sulfoxaflor, that reaches the soil system, is expected to degrad e ra pidly to the main degradate X

474 (aerobic soil 90 %tile t 1⁄2 = 0.4 day)

. Additionally, plant data suggest that the degradate X

- 474 is systemic as well and is expected to enter the plant from the soil. No data were presented on the
insecticidal activity of this degradate

.

g) Expected Behaviour of Sulfoxaflor in an Agricultural Setting

Sulfoxaflor is proposed for application to variable density fo liage of growing crops that depend s

on the timing of application (in all crops, the application window spans from seedlings to harvest). Upon application, only limited quantities of the pesticide are expected to be carried away by drift (to adjacent terre strial and aquatic systems) with the majority being deposited on target plants. Additionally, part of the applied pesticide is deposited into the soil with amounts being dependent on treated crop foliage density and wash

- off from foliar surfaces

.

Sulfoxaf lor deposited on the plant foliage is available for plant uptake . Plant residue data indicate that the parent compound enters the plant and is distributed into the foliage with only limited degradation (depending on the plant) . The same data also suggest t hat the degradate X

474 is systemic and can enter the plant from the soil (following its formation from rapid parent degradation). Parent entering the plant through foliage and X

- 474 entering the plant from soil may be a source of exposure depending on the agricultural practices. In contrast, sulfoxaflor, reaching the soil system directly and/or from foliage wash

- off, will be subjected to rapid degradation to X

- 474 (main soil degradate) which further degrades in most soils very slowly producing relatively l ow concentrations of X

- 540 and X

- 457.

h) Fish Bio c oncentration

No Fish b ioconcentration study was submitted due to the low K ow ( K ow @ 20 C & pH 7 = 6; Log
K ow = 0.802)

. Based on the low K ow , sulfoxa f lor is not expected to bio accumulate in aquatic systems. Although the parent compound has a high K OA which signifies a potential for bioaccumulation in terrestrial ecosystems, sulfoxaflor is n ot expected t o move into the air in appreciable concentrations based on its physical

- chemical properties

.47 3.2. 2. Measures of Aquatic Exposure

Aquatic exposures are quantitatively estimated for all of assessed uses using scenarios that represent high exposure sites for s ulfoxaflor use. Each of these sites represents a 10

- hectare field
that drains into a 1

- hectare pond that is 2 meters deep and has no outlet. Exposure estimates generated using the standard pon d are intended to represent a wide variety of vulnerable water bodies that occur at the top of watersheds including prairie pot holes, playa lakes, wetlands, vernal pools, man

- made and natural ponds, and intermittent and first

- order streams. As a group,

t here are factors that make these water bodies more or less vulnerable than the standard surrogate pond. Static water bodies that have larger ratios of drainage area to water body volume would be expected to have higher peak EECs than the standard pond sce nario . These water bodies will be either shallower or have large drainage areas (or both). Shallow water bodies tend to have limited additional storage capacity, and thus, tend to overflow and carry pesticide in the discharge whereas the standard pond ha s no discharge. As watershed size increases beyond 10 hectares, at some point, it becomes unlikely that the entire watershed is planted to a single crop, which is all treated with the pesticide. Headwater streams can also have peak concentrations higher than the standard pond, but th ese higher concentrations tend to persist for only short periods of time and are then carried downstream.

The objectives of this approach are to determine the EECs for the total toxic residues (TTR) of

p arent sulfoxaflor w hich represent the stressor of concern in aquatic systems

. Based on the
toxic ity of parent sulfoxaflor and important degradates

, i.e ., X

- 474 and X

- 540 to aquatic organisms, only parent and X

- 540 are considered in estimat ing the EECs of the stressor

.

How ever exposure is dominated by the degradate X

- 474 and i n order to understand the exposure of parent and its degradation products , EECs for parent and each of the individual constituents of
the parent residues , namely, parent

, X

- 474 , and X

- 540 were also est imated by running the following simulations:

a. Residues of interest runs for scenarios representing all crop use patterns with ground and aerial application ( a total of 50 runs using EXPRESS graphical interface);
b. Residues of interest runs for scenarios repr esenting all crop use patterns with aerial application; varied first application dates “5

- 15 runs through the long application window for this chemical” ( using PE

- 5 graphical interface);

c. Residues of interest runs for the same scenarios including two runs: one with drift and the other without drift (using PE

- 5 graphical interface); and
d. Parent alone runs for the same scenarios ( using PE

- 5 graphical interface )

.

Hereunder, is a complete list of the steps taken to perform modeling:

(1) Model Runs Residues of Inter est and Parent (all Crops Except Watercress)

a. Inputs Used for Modeling48 The first set of input parameters needed for modeling is labeled application parameters for various use patterns. Currently suggested labeled application parameters for sulfoxaflor ar e summarized in Table 14

.

Table 14

. Crop use patterns proposed for sulfoxaflor (Ground or aerial is permitted for all uses (refer to exceptions stated below this Table for Turf and ornament als)

Crop/Crop Group Crop Group(CG)
Or Subgroup (SG) Application Parameters: Maximum Application Rates/ Number& Minimum Intervals (Days) & Window Single (lb a.i./A) * Number Yearly (lb a.i./A) * Intervals Window **

Beans Beans 0.090 3

0.266 7

For crop s: from date of seedling to

pre

- harvest taking into
consideratio n the pre

harvest
interval (PHI) for each crop PHI ranges
from 1 to 14 days)

For trees:
from Pre

bloom to
mature fruit Berries SG 13

- 07F &G 0.090 3

Canola (Rapeseed) SG 20A 0.043 2 0.090 14

Citrus CG 10 0.133 2

0.266 7

Cotton Cotton 0.090 3 5
Fruits: Pome CG 11 0.133 2 7

Fruits: Stone CG 12 0.133 2 7

Grains (small grains) Small Grains 0.043 2 0.090 14
Ornamentals Ornamentals 0.133 2

0.266 7 Soybeans Soybeans 0.090 3

Tree Nuts CG 14 &
Pistachio 0.133 2 Turf grass Turf grass 0.133 2 Vegetables: Brassica (cole) leafy CG 5 0.090 3

Vegetables: Bulb SG 3

- 07 0.090 3

Vegetables: Cucurbit CG 9 0.090 3 Vegetables: Fruiting & Okra CG 8 & Okra 0.090 3 Vegetables: Leafy except
Brassica CG 4 0.090 3 Vegetables: Root & tuber
/Leaves CG 1 & 2 0.090 3 Watercress (commercial production) Watercress 0.090 3 Exceptions: (1) Only to commercial sod farms and grass grown for seed applied only by gr ound; and (2) May be applied aerially only to commercially grown ornamentals * Application rates entered into PRZM/EXAMS modeling are in Kg/ha= lbs/A multiplied by 1.121. For example: the maximum single application rate for beans= 0.09 x 1.121= 0.101 kg/ha and the yearly rate= 0.266 x 1.121= 0.298 kg/ha
** * Expected application date: This date is the date giving the highest EEC among multiple dates within the labeled application windows: from pre

- bloom to mature fruits for trees and fr om seeding to harvest for all others. Starting and ending dates for windows were taken from the scenarios. Multiple runs were executed for each scenario with dates of application The number of runs executed for each scenario. Actual application dates chose n for various scenarios are
included in Appendix A

.

The second set of input parameters needed for modeling involves choosing crop scenarios to represent the proposed use patterns. All available standard scenarios were used for modeling to49 represent label ed crop use patterns. A list of these scenarios along with the required application parameters is presented in Table 15

.

Table 15

. List of scenarios and application parameters used in mode ling

Crop/Crop Group Crop(s) Scenario Application Parameters (No.= Number of Applications)

Rate (lb a.i/A) X No. 1 Intervals (Days)

Beans Beans (dry & Lima, snab) MIbeansSTD 0.090 x 3 7

Beans Beans (dry & Lima, snab) ORsnbeansSTD 0.090 x 3 7

Berrie s Berries & Strawberry FLstrawberrySTD* 0.090 x 3 7
Canola (Rapeseed) Rape seed NDcanolaSTD 0.043 x 2 14

Canola mustard greens FLcabbageSTD 0.043 x 2 14

Canola Sesame CAcottonSTD* 0.043 x 2 14

Canola Sesame MScottonSTD 0.043 x 2 14

Canola Sesame MSsoy beanSTD 0.043 x 2 14

Canola Sesame NCcottonSTD 0.043 x 2 14

Citrus Citrus FLcitrusSTD 0.133 x 2 7

Citrus Citrus CAcitrusSTD* 0.133 x 2 7

Cotton Cotton NCcottonSTD 0.090 x 3 5

Cotton Cotton MScottonSTD 0.090 x 3 5

Cotton Cotton CAcottonSTD* 0.090 x 3 5

Fruits: Pome & Stone Apples, Peaches & Cherries CAfruitSTD* 0.133 x 2 7

Fruits: Pome Apples, pears & Quince NCappleSTD 0.133 x 2 7

Fruits: Pome Apples, pears & Quince ORappleSTD 0.133 x 2 7

Fruits: Pome Apples, pears & Quince PAappleSTD_V2 0.133 x 2 7

Fruits: Stone Peaches &/Or Cherries GAPeachesSTD 0.133 x 2 7

Fruits: Stone Peaches &/Or Cherries MICherriesSTD 0.133 x 2 7
Grains (small grains) Barley, Triticale & Wheat NDwheatSTD 0.043 x 2 14

Ornamentals X

- mass Trees ORXmasTreeSTD 0.133 x 2 7

Ornamentals Ornamentals CAnurserySTD_V2 0.133 x 2 7

Ornamentals Ornamentals MInurserySTD_V2 0.133 x 2 7

Ornamentals Ornamentals NJnurserySTD_V2 0.133 x 2 7

Ornamentals Ornamentals FLnurserySTD_V2 0.133 x 2 7

Ornamentals Ornamentals TNnurserySTD_V2 0. 133 x 2 7
Soybean Soybean MSsoybeanSTD 0.090 x 3 7

Tree Nuts Almonds CAalmondSTD* 0.133 x 2 7

Tree Nuts Filberts ORfilbertsSTD 0.133 x 2 7

Tree Nuts Pecans GAPecansSTD 0.133 x 2 7
Turf grass Turf FLturfSTD 0.133 x 2 7
Turf grass Turf PAturfSTD 0.133 x 2 750 Crop/Crop Group Crop(s) Scenario Application Parameters (No.= Number of Applications)

Rate (lb a.i/A) X No. 1 Intervals (Days) Vegetables: Brassica (cole) Leafy Several ** FLcabbageSTD 0.090 x 3 7
Vegetables: Bulb Onion (dry/green) & Pearl CAonionSTD* 0.090 x 3 7
Vegetables: Bulb Onion (dry/green) & Pearl GAOnionSTD* 0.090 x 3 7
Vegetables: Cucurbit Cucumber, Melons N JmelonSTD 0.090 x 3 7
Vegetables: Cucurbit Cucumber, Melons MOmelonSTD 0.090 x 3 7
Vegetables: Cucurbit Cucumber, Melons MImelonSTD 0.090 x 3 7
Vegetables: Cucurbit Cucumber, Melons FLcucumberSTD 0.090 x 3 7 Vegetables: Fruiting &
Okra Pepper FLpe ppersSTD 0.090 x 3 7 Vegetables: Fruiting &
Okra Tomato, Eggplant & Okra PAtomatoSTD 0.090 x 3 7 Vegetables: Fruiting &
Okra Tomato, Eggplant & Okra FLtomatoSTD 0.090 x 3 7 Vegetables: Fruiting &
Okra Tomato, Eggplant & Okra CAtomatoSTD* 0.090 x 3 7
Vegetables: Leafy Parsley ORmintSTD 0.090 x 3 7 Vegetables: Leafy except
Brassica Lettuce/Celery/ Spinach CAlettuceSTD 0.090 x 3 7
Vegetables: Root & tuber Carrot & Burdock (edible) FLcarrotSTD 0.090 x 3 7
Vegetables: Root & tuber Potatoes, Turnip& Ru tabaga MEpotatoSTD 0.090 x 3 7
Vegetables: Root & tuber Potatoes, Turnip& Rutabaga IDNpotatoSTD* 0.090 x 3 7

Vegetables: Root & tuber Sweet Potatoes NCSweetPotatoSTD 0.090 x 3 7
Vegetables: Root & tuber Beet & Ginseng MNsugarbeetSTD 0.090 x 3 7

1 Appli cation rates entered into PRZM/EXAMS modeling are in Kg/ha= lbs/A multiplied by 1.121. For example: the maximum single application rate for beans= 0.09 x 1.121= 0.101 kg/ha and the yearly rate= 0.266 x 1.121= 0.298 kg/ha * Scenarios with irrigation
** incl uding: Broccoli, Brussels sprouts, Cabbage, Cauliflower, Kale

The third set of input parameters needed for modeling is the fate and transport characteristics of
the chemical s being modeled. These parameters are summarized in Table 16 for the residues of
interest and parent runs.

Table 16

. Summary of PRZM/EXAMS input parameters for modeling Sulfoxaflor parent
and residues of interest

Input Parameter (Unit) Value for Residues of
Interest * (Parent) Reference (MRID No) and Notes

Molecular Weight g/mole 277.27 (for both) Product chemistry Henry’s constant (atm

- m 3

mol - 1 @ 2 5 o C) 1.2 x 10 - 11 (for both) Calculated51 Input Parameter (Unit) Value for Residues of
Interest * (Parent) Reference (MRID No) and Notes

Solubility in Water(mg/L) 570 (for both) Product chemistry Photolysis in Wate r (t1⁄2 in days @ pH 7) Stable (for both) Because the only photolysis degradate is included (MRID 478322

- 83)
Aerobic Soil Metabolism (90 th % t1⁄2 in days) 1,502 (0.4 ) (MRIDs 478655

- 78 and 478320

- 13) Hydrolysis (90 th % t1⁄2 in days) Stable (for both) (MRID 478 321

- 49)
All degradates are considered stable Aerobic Aquatic Metabolism (90 th % Whole system t1⁄2 in days) 1,577 (141) (MRID 478320

- 14) Anaerobic Aquatic Metabolism (90 th % Whole system t1⁄2 in days) 873 (672) (MRID 478322

- 77)

K
oc (Average in L/Kg) 14 (35) (MRID 478320

- 14)
Use Koc for X

- 540 Chemical Application Method (CAM) 2

Parameter Guidance 10 Application Efficiency 95% for aerial 99% for ground

Spray Drift Fraction Aerial (0.05) Ground: Airblast (0.01) and others (0.03)

* Half

- life values for the residues of interest are calculated from data for parent + X

- 474 + X

- 540 . Note that half

- life values reported earlier in the fate section are as specified either for parent or X

- 474 or X

- 540

.

b. Model Residues of Interest for Ground & Aerial Applications U sing EXPRESS Model runs were executed to determine if ground application gives higher EECs than aerial application. As expected, aerial application gave higher EEC s compared to ground application, therefore modeling concentrated on aerial application and t he results for ground application are
not included in this assessment

.

The resu lts for these multiple runs gave total

, drift and run

- off surface water associated EECs for parent (from parent runs), X

- 474 (estimated to be 88% of “ Residues of interest minu s parent”),
X

- 540 (estimated to be 12% of “ Residues of interest minus parent”) 11 , and EECs for the total of parent+ X

- 540+ X

- 474. Figure 10 shows an example graphical representation for some of these
results.

10 Guidance for Selecting Input Parameters in Modeling the Environmental Fate and Transport of Pesticides. URL: http://www.epa.gov/oppefed1/models/water/input_parameter_guidance.htm

11 Based on the maximum residues of 12% X

- 540 found in aerobic soil where it is expected to form.52 Peak

21

- day

60

- day Figure 10 . Surface water peak/21

- day/60

- day for the residues of interest EECs (μg/L) from
cotton and others

RQs were calculated for the EECs of the residues of interest ( total of parent+ X

- 540+X

- 474 ) and
based on the results o nly scenarios predicting risk were used to arrive at EECs for the TTR (parent+ X

- 540). The latter were calculated from parent alone runs as follows:

(1) Parent EECs from parent runs ; 0 10 20 30 40 50 60ParentX-474X-540TTRParentX-474X-540TTRParentX-474X-540TTR

Cotton (NC) Citrus (FL) Fruits (All

- CA)EECs (ppb)

Crop Drift

Run

- off

0 10 20 30 40 50 60ParentX-474X-540TTRParentX-474X-540TTRParentX-474X-540TTR

Cotton (NC) Citrus (FL) Fruits (All

- CA)EECs (ppb)

Crop Drift

Run

- off

0 10 20 30 40 50 60ParentX-474X-540TTRParentX-474X-540TTRParentX-474X-540TTR

Cotton (NC) Citrus (FL) Fruits (All

- CA)EECs (ppb)

Crop Drift

Run

- off53 (2) X

- 540 EECs from parent runs ( 12% of parent due to run

- off + 0% of parent due to drift).
This is based on the facts that the source of X

- 5 40 degradate is expected to be run

- off
from the soil only (X

- 540 did not form in laboratory aquatic systems) and that the maximum observed was 12%; and (3) EECs for the TTR by adding EECs from (1) and (2) above.

EECs for the TTR from the selected scenarios a re summarized in Table 17 for surface water and
in Table 18 for pore water.

Table 17

. Surface water EECs (μg/L) of the TTR for Sulfoxaflor use patt erns

Crop (State) Crop Group(s) Crop(s) Scenario DATE Peak 21

- day 60

- day

Beans (MI) CG

- 6 Beans (dry & Lima, snab) MIbeansSTD 29m07 5.5 5.31 5.05
Citrus (FL) CG

- 10 Citrus FLcitrusSTD 08m04 4.9 4.61 4.16

Cotton (NC) Cotton Cotton NCcottonSTD 23m09 4.6 4.4 6 4.26

Cotton (MS) Cotton Cotton MScottonSTD 26m08 4.6 4.35 4.02 Vegetables:
Brassica (cole) Leafy CG

- 5 Broccoli, Brussels sprouts, Cabbage, Cauliflower, Kale FLcabbageSTD 06m05 1.1 1.01 0.91 Vegetables: Bulb (GA) CG

- 3

- 07 Onion (dry/green) &
Pearl GAOni on_WirrigSTD 26m08 3.1 2.93 2.76 Vegetables: Leafy except
Brassica CG

- 4 Lettuce/Celery/ Spinach CAlettuceSTD 22m04 1.7 1.62 1.55 Vegetables:
Root & tuber CG

- 1& 2 Potatoes, Turnip& Rutabaga MEpotatoSTD 26m08 2.5 2.48 2.43 Vegetables:
Root & tuber CG

- 1& 2 Sweet Potatoes NCs weetp otatoSTD 26m08 4.2 4.01 3.81

Table 18

. Pore water EECs (μg/L) of the TTR for Sulfoxaflor use patterns

Crop (State) Crop Group(s) Crop(s) Scenario DATE Peak 21

- day 60

- day

Beans (MI) CG

- 6 Beans (dry & Lima, snab) MIbeansSTD 29m07 4.06 4.06 4.04

Citrus (FL) CG

- 10 Citrus FLcitrusSTD 08m04 2.67 2.67 2.63

Cotton (NC) Cotton Cotton NCcottonSTD 23m09 3.37 3.32 3.13

Cotton (MS) Cotton Cotton MScottonSTD 26m08 3.40 3.35 3.26 Vegetables: Brassica (cole) Leafy CG

- 5 Broccoli, Brussels sprouts, Cabbage, Cauliflower, Kale FLcabbageSTD 06m05 0.65 0.65 0.64 Vegetables: Bulb (GA) CG

- 3

- 07 Onion (dry/green)
& Pearl GAOnion_WirrigSTD 26m08 2.02 2.02 1.9954 Vegetables: Leafy except
Brassica CG

- 4 Lettuce/Celery/ Spinach CAlett uceSTD 22m04 1.33 1.33 1.33 Vegetables:
Root & tuber CG

- 1& 2 Potatoes, Turnip& Rutabaga MEpotatoSTD 26m08 2.48 2.47 2.45 Vegetables:
Root & tuber CG

- 1& 2 Sweet Potatoes NC s weetpotatoSTD 26m08 3.21 3.21 3.20

a) Estimation of Sediment Concentrations

E xposu re EECs to benthic sediment in aquatic systems was obtained for the highest and lowest pore water EECs ( Table 19 ).

Table 19

. Sediment EECs (μg/kg) for scenarios giving the highest and lowest pore water
EECs

(2) Model Runs for Watercress)

a. Inputs Used for Modeling

Watercress is typically cultivated in shallow, flowing water 2

- 3 inches deep 12 . The Agency does

not cur rently have a methodology for exposure assessment for crops cultivated in flowing water.
In this assessment, conservative EEC s resulting from application of sulfoxaflor to watercress

w ere quantitatively obtained using Tier 1 Rice Model. It is noted however , that conservatism in the estimates comes from two assumptions:

(1) T he assumption that the pesticide is applied to water although commercial production appear to indicate that the pesticide is to be applied only to the plant foliage with no water present ; a nd (2) The assumption that surface water EECs is equal to that expected by direct application of the pesticide into a rice paddy. Therefore, modeling results were characterized to reflect
effects of application efficiency (fraction of amount applied which is i ntercepted by the crop), degradation of the pesticide in water after application, and effects of flow through and downstream from the area of cultivation.

Labeled application parameters for watercress calls for a single application of 0.09 lbs a.i/A with

a seasonal maximum of three applications totaling 0.266 lbs a.i/acre and a minimum of 7

- day

12 http://www.naturesherbal.com/Watercress.htm and

http://edis.ifas.ufl.edu/mv151 Crop (State) Crop Group(s) Crop(s) Scenario DATE Peak 21

- day 60

- day

Beans (MI) CG

- 6 Beans (dry & Lima, snab) MIbeansSTD 29m07 7.19 7.18 7.15 Vegetables:
Brassica (cole) Lea fy CG

- 5 Broccoli, Brussels sprouts, Cabbage, Cauliflower, Kale FLcabbageSTD 06m05 1.15 1.14 1.1355 reapplication interval. Other input parameters, for the T ier 1 R ice M odel include t he a verage K oc ( 30 L/Kg for parent).

In modeling, parent sulfoxaflor was consid ered to be the stressor of concern due to the fact that the degradate X

- 540 is not expected to form in aquatic systems.

b. Results for Modeling

The EECs resulting from the currently proposed three applications is 2 78 ppb of the T TR which
would be parent s ulfoxaflor alone because X

- 540 is not expected to form in aquatic systems. For a single application, the EEC is 9 3 ppb T T R while it is 18 6 ppb T T R following two applications. These initial concentrations estimated by the Tier 1 Rice model assume sulfoxaflo r application to watercress growing in a rice paddy containing static water. The only process simulated by the model is partitioning of the applied chemical between the 10

- centimeter deep water column and
the 1

- centimeter deep sediment layer of the paddy. The partitioning is based on the pesticide’s partitioning constant (K d = 0.3 L/Kg calculated by the mode from K oc of 30 L/kg). Other assumptions for the Tier 1 Rice model include:

• All applications are applied at time zero (no application intervals can be simulated);

• The application efficiency is 0.0 ( i.e

. , none of the pesticide remains on the watercress plants , which is not a realistic assumption );

• Peak concentrations of the parent occur simultaneously; and

• No degradation occurs in the paddy (the model ass umes the residues remain at the initial concentration in the water indefinitely).

Modeling results from Tier 1 Rice model gives concentrations expected in the rice paddy. However, E ECs in surface water outside the rice paddy are expected to be affected b y many factors. These factors and their impact on modeled E ECs are discussed below :

(1) Impact of application efficiency

As stated above, the initial concentrations, in the rice paddy for the TTR of sulfoxaflor are : 93 ppb for single application 186 ppb for two applications, and 278 ppb for three applications

. These EECs are based on the assumption that the fraction of amount applied which is intercepted by the crop ( i.e ., the application efficiency) is zero which is not a realistic assumption. Figure 11 shows the possible impact of application efficiency on the initial concentration in the rice paddy water. Any interception of the applied pesticide (increase in efficiency), by the watercress plant, is expected to red uce EECs on the assumption that the pesticide is reduced by plant intake through leaves before it is washed

- off into the soil. In case of sulfoxaflor, the systemic nature of the pesticide increases the chance of this process to occur causing reduction of t he EEC values.56 Figure 11

. Impact of application efficiency on determined EECS for Surface Water

(2) Impact of pesticide degradation

Under field conditions, the initial concentration estimated by the T ier 1 R ice M odel ( i.e ., EECs in the rice paddy) is expected to be reduced by degradation. The impact of degradation on the
T TR of sulfoxaflor is only significant only after 100 days and repeated application increased the EECs after 1 year about 10 fold. This is due to observed persis tence of parent in water/sediment system (90 th % t 1⁄2 = 141 days). The effect of d egradation on EECs is depicted in Figure 12

. 93

65 46 185

130

93

0 278

222

167

111

56

0 0 50 100 150 200 250 300

0 0.2 0.4 0.6 0.8 1 One Application

Two Applications

0 50 100 150 200 250 300

0 100 200 300 400 Aqueo us Co ncentratio n (μg/L)

Days After Application Rice Paddy EECs vs Time

EEC after the 3 rd application

EEC after the 1 st application EEC after the 2 nd a pplication57 Figure 12

. Impact of pesticid e degradation on determined EECs in the rice paddy following one (blue line), two (red line) and three (green line) application

In Figure 12 , the initial EEC value for one application ( 93 ppb of the T TR ) may be re duced by degradation to 15 ppb within a one

- year period

. The in itial EEC v alue after two applications (184 ppb of the T T R ) may be reduced by degradation to 162.6 ppb within a one

- year period

. Similarly, the initial EEC value f ollowing three applications (2 7 5 ppb of the T T R ) may be reduced by degradation to 149 ppb within a one

- year period

.

(3) Impact of downstream movement from site in flowing water through watercress
cultivated areas

Under actual conditions of watercress cultivation, the amount of pesticide which reaches the stream water will be removed continuously downstream from the site at which it is applied by advection in the flowing water. The rate of removal depends on the rate of flow through the site. River velocity varies from day to day based on the volume of flow and changing cross

- sectional area. Typical ranges of velocity vary from zero (at the time of tidal flow direction change) to 7 miles per hour

. 13 The Mississippi River ranges from 1.2 to 3 miles per hour depending on the
amount of flow an d the reach in which it is measured. The pesticide in the flowing water will also spread from the center of mass during the flow. Figure 13 presents the distance downstream of the center of mass of the applied sulf oxaflor depending on the flow rate of the stream (in miles/hour and in feet/second).

13 http://hypertextbook.com/facts/2006/Nerva naGaballa.shtml58 S

t

r

e

a

m

F
l

o

w

R

a t

e

Figure 13

. Expected downstream movement, from site of application of sulfoxaflor, in flowing water in one Day

The above presentation sugg ests that a combination of application efficiency, pesticide degradation and stream flow are expected to produce surface water concentration values lower
than the conservative value s of 93 to 264 pp b

.

(4) Impact of Agronomic Practices

Two important factors c an impact EECs arrived at by rice modeling, namely:

(a) Expected usage or acreage that may be treated with the chemical. The EEC s from Tier 1
R ice M odel are not adjusted for percent crop area (PCA ). Lower EEC s are expected as a
result of such an adjustment du e to the fact that reported watercress acreage is limited

. In 2007, watercress production totaled nearly 700 acres nationwide

, mainly distributed
between three states Florida ( 426 acres ) , California ( 151 acres ) and Hawaii ( 15 acres) 14

. Other states where watercress is grown on only few acres include: Alabama, Maryland, Michigan, Pennsylvania, Tennessee and West Virginia. Additionally, the label will further reduce acreage that could potentially be treated with sulfoxaflor as it will limit application of th e chemical to “Commercially grown watercress”; and

14 http://www.agcensus.usda.gov/Publications/2007/Full_Report/usv1.pdf 

### 0 0.5 1 1.5

2 2.5

3 3.5

4 4.5 5

0 20 40 60 80 100 120 Flow Rate (miles/hour)

Flow Rate (feet/second)

Downstream Distance from Center of Mass (Miles)

Downstream Distance in One Day (One day movement, in miles, from center of mass of applied59 (b) Known agronomic practices in “ c ommercially grown watercress” are different from those assumed for rice. These practices include 15 :

• Use of flow

- through irrigation: water flows through from the top of the c rop beds over the surface of beds (having an established gradient) to be collected and pumped back to the top of the beds

, i.e ., same water is circulated.

• Beds are completely drained prior to, during and after pesticide application

• Depth of flowing water i s kept at a maximum depth of one inch.

It is noted that none of these factors were taken in consideration in modeling EECs for sulfoxaflor. However, the most important aspect of the above practices are water reuse (reduce possible contamination for surfa ce waters) and draining of the beds prior to, during and after pesticide application. This limits direct application of the pesticide to water and gives time for its degradation of the parent sulfoxaflor into X

- 474 reducing the contribution of parent sulfo xaflor
to the EEC s (i.e., reducing surface water c ontamination with the stressor “ parent sulfoxaflor ” a s the only expected contaminant would be from parent drift and from X

- 474 (not considered as part of the stressor in this assessment) . In this case, surf ace water EECs for watercress could be represented by the CA lettuce scenario ( Table 20 ).

Table 20

. EECs for watercress use when watercress beds are drained prior to, during and after pesti cide application sulfoxaflor

Crop (State) Crop

Group(s) Crop(s) Scenario DATE Peak 21

- day 60

- day

(1) EECs for surface water (ppb)

Leafy vegetables CG

- 4 Lettuce/Celery/ Spinach CAlettuceSTD 22m04 1.7 1.62 1.55

(2) EECs for pore water (ppb)

Leafy vegetables CG

- 4 Lettuce/Celery/ Spinach CAlettuceSTD 22m04 1.33 1.33 1.33

b) Aquatic Exposure Monitoring (Field Data)

This is a new pesticide and therefore n o data were identified to provide information on aquati c monitoring.

3.2.3 Terrestrial Exposure Assessment

Terrestrial wildlife exposure estimates are typically calculated for bird and mammals, emphasizing a dietary exposure route for uptake of pesticide ac tive ingredients. These exposures

15 Information is taken from a presentation to EPA by B&W of Florida, a commercial wate rcress
grower.60 are considered as surrogates for terrestrial

- phase amphibians as well as reptiles. For exposure to terrestrial organisms, such as birds and small mammals, pesticide residues on food items are estimated, based on the assu mption that organisms are exposed to a single pesticide residue in a given exposure scenario.

3.2.3.1

. Terrestrial Vertebrate Exposure Modeling

F or sulfoxaflor spray applications, estimation of pesticide concentrations in wildlife food items
focuses o n quantifying possible dietary ingestion of residues on vegetative matter and insects. As described earlier, t he EFED terrestrial exposure model T

- REX ( version 1.5 .1 ) is used to estimate exposures and risks to avian and mammalian species. Input values use d for estimating avian and mammalian exposure risks to sulfoxaflor are summarized in Table 21

.

Table 21

. Input parameters used in T

- REX v1.5 to determine terrestrial EECs for the
maximum sulfoxaflor spray application scenarios. Input Variable Parameter Value Source Maximum application rate and frequency * 0. 133 lb a.i./A x 2

0.090 a.i /A x 3 Product Label

Minimum Application
Interval 5

- 14 days Product Label

Foliar half

- life 12.3 days Sul foxaflor residue

- decline
data ( MRID 48755703 ) * Crop uses applicable to these use patterns are shown in Table 4

.

For deriving a sulfoxaflor

- specific foliar dissipation rate , a n abundance of residue

- decline data

w as available from registrant

- submitted field residue trials (MRID 48755703). In selecting data sets for calculating the foliar dissipation half life values, guidelines provided in the T

- REX
User’s Guide was followed. 16 Specifically, residue

- decline data s ets needed to meet the following criteria in order to be considered for half life calculation:
1. Day 0 measurement of residues available
2. At least 3 measurement times with residues above the limit of detection
3. R 2 values (ln concentration vs. time) of 0.7 or h igher
4. Statistical significance of regression coefficient of 0.1 or lower

Base d on these criteria, a total of 44 foliar DT 50 values were available for sulfoxaflor ( Appendix
B ) . These DT 50 values consisted of measu rements on a variety of crops and plant matrices ( e.g ., foliage, fruit, seeds, grains and roots. In situations were multiple trials were available within a crop and crop matrix ( e.g ., multiple values for head lettuce), the DT 50 values were averaged. The

r esulting 25 DT 50 values averaged within a crop matrix are shown in Figure 14 . These foliar
DT 50 values ranged from 1.8 to 29, with a calculated 90 th percentile DT 50 of 12.3 days based on log transformed values.

16 http://www.epa.gov/oppefed1/models/terrestrial/trex/t_rex_user_guide.htm61 Figure 14

. Summary of foliar dissipation half life (DT50) values for sulfoxaflor

It appears from examination Figure 14 that the crop matrix exerts some influence on the DT 50 values , with residues measured in fruits and seeds/grains generally having the longest DT 50 values . With one exception, average crop matrix DT 50 values measured in plant foliate (leaves, whole plant, straw, hay) are about 4 days or less.

3.2.3. 2

. Terrestrial Exposure Monitoring (Field Data)

Sulfoxaflor is a new pesticide and therefore

, no monitoring data were identified to provide
information on chemical concentrations in terrestrial ecosystems

. Exp erimental data documenting residues in plant tissues relevant to exposure of bees to sulfoxaflor are described in
Section 5.1.

3.2.3. 3

. Non

- Target Plant Exposure Assessment

Tier I seedling emergence and vegetative vigor toxicity tests did not establish EC 25 estimates

, i.e ., the EC 25 values were higher than the highest treatment rate tested, for sulfoxaflor. Specifically, no detrimental effects ≥25% were observed for any test species at rates up to 0.357
lb a.i /A (MRID 47832425 and 47832427 ) which is approximately 2.5X the maximum single application rate of 0.133 lb a.i /A). Furthermore, NOAEC values for terrestrial plants also
exceeded t he maximum single application rate of sulfoxaflor tested . Therefore, no exposure modeling was conducted for terrestrial plants since non

- listed and listed species LOC of 1.0
could not be exceeded. 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

1 10 100Cumulative Frequency (%)



### DT50 (days) foliage

fruit

heads

roots

seeds/grain Min=1.8

Max = 29
90th=12.362 

### 4. **E COLOGICAL**  

### E **FFECTS** 

### C **HARACTERIZATION**

In screening

- level ecological risk assessments, effects characterization describes the types of effects a pesticide can produce in an aquatic or terrestrial organism. This characterization is based on registrant

- submitte d studies that describe acute and chronic effects toxicity information for various aquatic and terrestrial animals and plants. A summar y of the results of the registrant

submitted toxicity studies used to characterize effects for this risk assessment is p rovided in Appendix C (all taxa except bees) and Appendix D (for bees)

. Toxicity testing reported in this section does not represent all species of birds, mammals, or aqua tic organisms. Only a few surrogate species for both freshwater fish and birds are used to represent all freshwater fish (2000+) and bird (680+) species in the United States. For mammals, acute studies are usually limited to Norway rat or the house mouse . Estuarine/marine testing is usually limited to a crustacean, a mollusc, and a fish. Also, neither reptiles nor amphibians are tested. The risk assessment assumes that avian serve as a surrogate for the terrestrial

- phase amphibians and reptiles. This assessment also assumes that freshwater fish serve as a surrogate for aquatic

- phase amphibians.

4.1 Aquatic Effects

A summary of toxicity data for the most sensitive species within each taxonomic group of aquatic organis ms is provided in Table 22 ; the most sensitive tested species in each of the taxonomic groups is shown in bold

. All submitted data for sulfoxaflor w ere with TGAI ; no technical end product ( TEP ) data were submitted with aquatic organisms

.

Table 22

. Summary of sulfoxaflor toxic ological endpoints for aquatic organisms

Taxa Species Tested Toxicity Exposure (1) Toxicological Endpoint (mg a.i./L) MRID (Classification)

Freshwater Fish Rainbow t rout ( Oncorhynchus mykiss) Common carp

( Cyprinus carpio) Bluegill sunfish

( Lepomis macrochirus ) Acute LC 50 (96

- hr): >387

LC 50 (96

- hr): >402

LC 50 (96

- hr): >363 47832111 (Acceptable)

47832113 (Acceptable)

4783212 (Supplemental)

Rainbow trout

( Oncorhynchus mykiss) Acute ( X11719474) LC 50 (96

- hr): > 478 47832105 (Acceptable)

Fathead minnow

( Pimephales promelas) Chronic 30

- d NOAEC (ELS): 0.66 (reduced dry wt.) 47832126 (Supplemental)

Freshwater
Invertebrate Water flea ( Daphni a magna) Acute EC 50 (48

- hr): >400 47832114 (Acceptable)

Acute ( X11719474) EC 50 (48

- hr): >205 47832106 (Acceptable)

Chronic NOAEC (21

- day): 50.5 (reduced reproduction) 47832127 (Acceptable) Marine/Estuarine

Fish Sheepshead minnow ( Cyprinodon variegatus ) Acute LC 50 (96

- hr): 266 47832110 (Acceptable)63 Taxa Species Tested Toxicity Exposure (1) Toxicological Endpoint (mg a.i./L) MRID (Classification)

Chronic NOAEC(30

- d): 1.2 (reduced length) 47832129 (Acceptable)

Marine/Estuarine

Invertebrate Mysid shrimp ( Americamysis bahia ) Acute LC 50 (96

- hr): 0.64 47832117 (Acceptable)

Chronic NOAEC: 0.11 (time to first brood) 47832128 (Acceptable)
Eastern oyster

( Crassostrea virginica) Acute EC 50 (96

- hr): 86.5 47832115 (Acceptable)

Freshwater

Benthic
Invertebrates Midge ( Chironomus dilutus ) Subchronic NOAEC (10

- d): 0.0 99 mg a.i /L pore water (dry wt.)

NOAEC (10

- d): 0.049 mg a.i /kg dry sediment (dry wt.) 47832109 (Acceptable)

Midge

( Chironomus riparius) C hronic NOAEC (28

- d): 0.0 37 mg a.i /L pore water (emergence)

NOAEC (28

- d): 0.05 mg

a.i /kg dry sediment (emergence) Gerke A (2009) (Sup plemental)

Aquatic Non

vascular Plants Freshwater diatom ( Navicula pelliculosa) EC 50 (96

- h): 81.2 (B iomass )

NOAEC (96

- h): 3.54 (R,Y,B) ( 2 ) 47832123 (Acceptable)

Green alga

(Pseudokirchneriella subcapitata) EC 50 (96

- h): >101 (R,Y,B)

NOAEC (96

- h) : 101 (R,Y,B) 47832121 (Acceptable)

Bluegreen alga

( Anabaena flos

- aquae) EC 50 (72

- h): 83.8 (Y ) NOAEC (72

- h): 12.0 (G,Y,B) 47832124 (Supplemental)

Marine diatom ( Skeletonema costatum ) EC 50 (96

- h): >103 (R,Y,B) NOAEC (96

- h): 103 (R,Y,B) 47832122 (Supplemental)

Aquatic Vascular Duckweed (Lemna gibba) EC 50 (7

- d): >99 NOAEC (7

- d): 99 (dry wt, frond count) 47832125 (Acceptable)

(1) Test substance is TGAI with purities > 95%

. ( 2 ) R= growth rate; Y= yield; B= biomass integral; Toxicity values show n in bold are used for risk estimation The most sensitive endpoints shown in bold were used for risk estimation.

4.1.1 Acute Toxicity to Fish

Sulfoxaflor is classified as practically non

- toxic on an acute exposure basis, with 96

- h LC 50 values of >400 m g a.i./L for all three freshwater fish species tested (bluegill, Lepomis macrochirus ; rainbow trout, Oncorhynchus mykiss ; and common carp, Cyprinus carpio ; MRID 47832112, 47832111, and 47832113, respectively). Mortality was 5% or less at the highest test64 treatments in each of these studies. Treatment

- related sublethal effects included discoloration at the highest treatment concentration (100% of fish at 400 mg a.i./L for bluegill) and fish swimming on the bottom (1 fish at 400 mg a.i./L for rainbow trout) . No other treatment

- related sublethal effects were reported. For a n estuarine/marine sheepshead minnow ( Cyprinodon variegatus ; MRID 47832110), sulfoxaflor was also practically non

- toxic with an LC 50 of 288 mg
a.i./L . Sublethal effects included loss of equilibrium or lying on the bottom of aquaria at 200 and 400 mg a.i./L . The primary degradate of sulfoxaflor (X474) is also classified as practically non

toxic to rainbow trout on an acute exposure basis ( 96

- h LC 50 >500 mg a.i./L ; MRID 47832105).

4.1.2 Ch ronic Toxicity to Fish

Adverse effects from chronic exposure to sulfoxaflor were examined with two fish species (fathead minnow, Pimephales promelas, MRID 47832126; and sheepshead minnow; MRID 47832129) during early life stage toxicity tests. For fathead minnow, the 30

- d NOAEC is 5 mg
a.i./L based on a 30% reduction in mean fish weight relative to controls at the next highest concentration ( LOAEC= 10 mg a.i./L ). No statistically significant and /or treatment

- related effects were reported for hatching succe ss, fry survival and length. For sheepshead minnow, the
30

- d NOAEC is 1.3 mg a.i./L based on a statistically significant reduction in mean length (3% relative to controls) at 2.5 mg a.i./L . No statistically significant and /or treatment

- related effects

we re reported for hatching success, fry survival and mean weight.

4.1.3 Acute Toxicity to Aquatic Invertebrates

The acute (water column) toxicity of sulfoxaflor was evaluated for one freshwater species (waterflea, Daphnia magna ; MRID 47832114 ) and two sal twater species (mysid shrimp, A

. bahia ; MRID 47832117 and E astern oyster, Crassostrea virginica ; MRID 47832115 ). For D.

magna , the 48

- h EC 50 is >400 mg a.i./L , the highest concentration tested

. For E astern oyster, new shell growth was significantly redu ced at 120 mg a.i./L (75% reduction relative to control).
The 96

- h EC 50 for shell growth is 93 mg a.i./L

. No mortality occurred at any test concentration. Mysid shrimp are the most acutely sensitive invertebrate species tested with sulfoxaflor based on

w ater column only exposures , with a 96

- h LC 50 of 0.67 mg a.i./L

. The primary degradate of sulfoxaflor (X474) is also classified as practically non

- toxic to D. magna (EC 50 >240 mg a.i./L ; MRID 47832106).

4.1.4 Chronic Toxicity to Aquatic Invertebrates

The chronic effects of sulfoxaflor to D

. magna were determined in a semi

- static system over a period of 21 days to nominal concentrations of 6.25, 12.5, 25, 50 and 100 mg a.i./L (MRID
47832127 ) . Adult mortality, reproduction rate (number of young), length of the surviving adults, and days to first brood were used to determine the toxicity endpoints. In this flow through study,

t he test substance was stable and the mean

- measured concentrations approximated the nominal concentrations (100

- 101% of nominal); there fore, the biological endpoints are reported as
nominal concentrations. No treatment

- related effects on adult mortality or adult length were observed. The reproduction rate and days to first brood were significantly (p<0.05) different in65 the 100 mg a.i./L t est group ( 40% reduction in mean number of offspring; 35% increase in time to first brood). No significant effects were observed on survival, growth or reproduction at the
lower test concentrations. The 21

- day NOAEC and LOAEC were determined to be 50 and 1 00 mg a.i./L , respectively.

The chronic effects of sulfoxaflor to mysid shrimp were determined in a flow

- through system over a period of 28 days to nominal concentrations of 0.063, 0.13, 0.25, 0.50 and 1.0 mg a.i./L (MRID 47832128 ). Mortality of parent ( F 0 ) and first generation ( F 1 ) , reproduction rate of F 0 (number of young), length of the surviving F 0 and F 1 , and days to first brood by F 0 were used to
determine the toxicity endpoints. Complete F 0 mortality (100%) was observed at the highest test

concentr ation of 1.0 mg a.i./L within 7 days; no treatment

- related effects on F 0 /F 1 mortality, F 0 reproduction rate, or F 0 /F 1 length were observed at the lower test concentrations , which is somewhat unexpected given the reported acute LC 50 0f 0.67 mg a.i./L descri bed previously . The days to first brood by F 0 were significantly (p<0.05) different in the 0. 25 and 0.50 mg a.i./L test groups (both means: 17.0 days to first brood) relative to the controls (mean: 17.8 days to first brood) , although this represents just a 4.5% increase relative to controls. N o significant effects on days to first brood by F 0 were observed at the lower test concentrations. T he 28

- day NO A EC
and LOAEC were determined to be 0.1 1 mg and 0.25 mg a.i./L , respectively

.

Although the chemical prope rties of sulfoxaflor ( i.e ., low K ow , low partitioning to solids) would not result in a requirement for submitting sediment toxicity testing, t he subchronic toxicity of sulfoxaflor to benthic invertebrates via sediment exposure was investigated for larvae o f the freshwater chironomid, Chironomus dilutus (MRID 47832109). For risk estimation, toxicity endpoints based on concentrations in pore water and sediment are used. Following a 10

- day sub

acute exposure to C 14

- labeled sulfoxaflor administered in spiked s ediments, 43% and 0% survival was observed at mean sediment concentrations of 0.17 and 0.36 mg a.i

. /kg dry sediment, respectively

. Analysis of overlying water samples taken from the 1.0 mg a.i./L treatment via
HPLC/MS/MS indicate that nearly all of the TR R was parent compound over the 10

- day study duration (only 3% was detected as X

- 474 by day 10). Survival in all other treatments (0.025 to 0.09 mg a

. i

. /kg dry sediment and controls) was 93% or greater. The NOAEC based on dry weight is 0.0 49 mg TRR/kg dry sediment with a 31% reduction in mean dry weight occurring in the next highest treatment (0.09 mg TRR/kg dry sediment). This NOAEC is equivalent to 0.099 mg a.i./L (mean

- measured) in pore water.

The chronic toxicity of sulfoxaflor to midge larvae ( C

. rip arius ) in whole sediment was
determined using spiked water dosing

. Midge s were exposed to sulfoxaflor applied to the overlying water in a static system over a period of 28 days to nominal concentrations of 0.065, 0.13, 0.25, 0.50 and 1.0 mg a.i./L

. Emergen ce, development rate and survival were used to
determine the toxicity endpoints. T he TRR in the overlying water decreased to about 72

- 81% of nominal after 28 days which was attributed to the test substance being incorporated into the pore
water and sedimen t based on analytical results from the study. Approximately two

- thirds of the residues in the overlying water of the 0.100 mg a.i./L treatment were determined to be sulfoxaflor, while X474 comprised the remaining third; therefore, the biological endpoints are reported as mean

- measured TRR concentrations (0.00142, 0.00286, 0.00604, 0.0112, 0.0225, 0.0455 and 0.0949 mg TRR/L overlying water). Emergence was significantly lower at 0.094966 mg TRR/L (mean: 70%) relative to controls (mean: 91%). No treatment

- relate d effects on development rate were observed. The 28

- day NO A EC was determined to be 0.04 6 mg TRR/L for overlying water, 0.037 mg TRR/L for pore water, and 0.05 mg/kg for dry sediment

. Since
effects on midge reproduction were not quantified per USEPA Agency

- wide guidelines for chronic sediment toxicity testing (USEPA

, 2000), this test is classified as supplemental.

4.1.5 Toxicity to Aquatic Plants

Sulfoxaflor exhibited relatively low toxicity to aquatic non

- vascular plants . The most sensitive aquatic nonv ascular plant is the freshwater diatom, Navicula pelliculosa

, with a 96

- h EC 50 of 81.2 mg a

. i

. /L ( MRID 47832123) Similarly, sulfoxaflor was not toxic to the freshwater vascular aquatic plant, Lemna gibba , up to the limit amount, as indicated by a 7

- d EC 50 for frond count, dry weight and growth rate of >100 mg a.i./L (MRID 47832125) with n o significant adverse effects on these endpoints observed at any treatment concentration

.

4.2 Terrestrial Effects

A summary of toxicological endpoints for terrestr ial organisms exposed to sulfoxaflor is provided in Table 23

.

Table 23

. Summary of sulfoxaflor t oxicological e ndpoints for terrestrial organisms.

Taxa Species Type of Toxicity (Purity) (1 ) Toxicological Endpoint MRID

Birds Bobwhite Quail (Colinus virginianus) Acute (oral) (95.6%; TGAI) LD 50 : 676 mg/kg bw 47832101 (Acceptable)

Zebra finch ( Poephila guttata) LD 50 : >80 mg/kg bw 47832072 (Supplemental)

Bobwhite Quail (Colinus virginia nus) Acute (oral)

X11719474 (99.5%) LD 50 : > 2,250 mg/kg bw 47832073 (Acceptable)
Bobwhite Quail (Colinus virginianus) Suba cute (dietary) (95.6%; TGAI) LC 50 (5

- d): > 5,620 ppm 47832074 (Acceptable)

Mallard duck ( Anas platyrhynchus) LC 50 (5

- d): >5,6 20 ppm 47832104 (Acceptable)

Bobwhite Quail (Colinus virginianus) Chronic (95.6%; TGAI) NOAEL (20 wk): 1,000

ppm (81 mg ai/kg bw/d) 47832119 (Acceptable)

Mallard duck ( Anas platyrhynchus) NOAEL (20 wk): 200 ppm (26 mg ai/kg bw/d) 47832120 (Accepta ble)

Mammals Rat ( Rattus norvegicus) Acute (oral) (95.6%; TGAI) LD 50 1000 mg ai/kg bw (female) 47832144 (Acceptable)

Mouse (Mus musculus) LD 50 750 mg ai/kg bw 47832040 (Acceptable)67 Taxa Species Type of Toxicity (Purity) (1 ) Toxicological Endpoint MRID

Rat ( Rattus norvegicus)

Rat ( Rattus norvegicus) Acute (oral) GF

- 2372 TEP (40%) LD 50 >2 000 mg ai/kg bw 47832505 (Acceptable)

Acute (oral) GF

- 2032 TEP (22%) LD 50 >5 000 mg ai/kg bw 47832407 (Acceptable)

Chronic dietary (95.6%; TGAI) NOAEL (two generation): 100 ppm (6.07 mg ai/kg bw) (decreased neonatal survival) 47832 142 (Acceptable)

Terrestrial
Invertebrates Honey bee, adult ( Apis mellifera) Acute (contact) TGAI LD 50 (72

- h): 0.379 ug a.i./bee 47832102 (Acceptable) Acute (contact) TEP:

GF

- 2032

- SC LD 50 (48

- h): 0.130 ug a.i./bee 47832419 (Acceptable) Acute (cont act) TEP:

GF

- 2372

- WG LD 50 (48

- h): 0.224 ug a.i./bee 47832511 (Acceptable)

Acute (oral) TGAI LD 50 (48

- h): 0.146 ug a.i./bee 47832103 (Acceptable) Acute (oral) TEP: GF

2032

- SC LD 50 (48

- h): 0.052 ug a.i./bee 47832417 (Acceptable) Acute (oral)

X117194 74 LD 50 (96

- h): >100 ug a.i./bee 47832107 (Acceptable) Acute (oral)

X11721061 LD 50 (48

- h): >104 ug a.i./bee 48445809

Acute foliar residue ( TEP: GF

- 2372

- WG) 24

- h aged residue mortality: 14% ( 0.089 lb ai/A or 100 g ai/ha) 15% ( 0.178 lb ai/A or 200 g ai/ha) 47832512 (Acceptable)

Acute foliar residue ( TEP: GF

- 2032

- SC) 3

- h aged residue mortality: 4% (200 g ai/ha) 47832420 (Acceptable)

Honey bee, larvae

( Apis mellifera) Chronic, single dose (TGAI) NOAEC (7

- d): 0.2 μg a.i./bee larvae 48755602 (Supp lemental) Chronic, repeated dose (TGAI) NOAEC (7

- d): 0.02 μg a.i./bee larvae 48755603 (Supplemental)

Bumble bee, adult ( Bombus terrestris) Acute (contact) (TEP:

GF

- 2032

- SC ) LD 50 (72

- h): 7.55 μg a.i./bee 47832418 (Supplemental) Acute (oral) (TEP: G F

2032

- SC ) LD 50 (72

- h): 0.027 μg a.i./bee 47832418 (Supplemental)

Terrestrial

plants Multiple species Tier 1

– Seedling Emergence (TEP: GF

2032

- SC ) EC 25 (21

- d): > 0.357 lb ai/A (>400 g ai/ha)

NOAEC = 0.357 lb ai/A ( 400 g ai/ha ) 47832427 (Acceptable)68 Taxa Species Type of Toxicity (Purity) (1 ) Toxicological Endpoint MRID

Terr estrial

plants Multiple species Tier 1/ 2

– Vegetative Vigor (TEP: GF

- 2032

- SC ) EC 25 (21

- d): > 0.178 l b ai/A (>200 g ai/ha)

NOAEC = 0.178 l b ai/A ( 200 g ai/ha ) 47832425 (Supplemental)

The most sensitive endpoints shown in bold were used for risk estimation.

4.2.1 Toxicity to Birds

Based on an acute oral LD 50 of 676 mg a

. i

. /kg bw for bobwhite quail ( Colinus virginianus )

, sulfoxaflor is considered slightly toxic to birds on an acute oral exposure basis (MRID 47832101) . The acute oral LD 50 could not be deter mined for the passerine zebra finch ( Taeniopygia guttata ; MRID 47832072) due to regurgitation at treatments above 29 mg a.i./kg
bw ). In this study, 40% mortality was observed at the highest dose (200 mg a.i./kg bw) with no mortality occurring at lower dose s. In the controls and lowest dose (29 mg a.i./kg bw), no birds regurgitated. A dose

- dependent increase in the rate of regurgitation was observed at higher treatments (1/10 at 49 mg a.i./kg bw; 2/10 at 80 mg a.i./kg bw; 7/10 at 132 mg a.i./kg bw; 10/10

a t 200 mg a.i./kg bw). Sublethal effects at 49 mg a.i./kg bw and above included ruffled appearance, loss of coordination, lower limb weakness, prostrate posture, loss of righting reflex, convulsions and lethargy)

. The LD 50 to estimated to be >80 mg a.i./k g bw based on the lowest level at which ≤20% birds regurgitated and no mortality occurred. Thus, even one assumes all the birds that regurgitated their dose would have died, the LD 50 would be somewhere between 80 and 132 mg a.i./kg bw (20% and 70% regurgit ation)

.

On a subacute, dietary exposure basis, sulfoxaflor is classified as practically nontoxic to birds,
with 5

- d LC 50 values of >5620 mg/kg

- diet for mallard ducks ( Anas platyrhynchus ) and bobwhite quail (MRID 47832104 and 47832074, respectively). The NOAEL from these studies is 5620 mg/kg

- diet as no treatment related mortality of sublethal effects were observed at any treatment. Similarly, the primary degradate (

- 474) is classified as practically nontoxic to birds on an acute
oral exposure basis with a LD 50 of >2250 mg a.i./kg bw (MRID 47832073).

In two chronic, avian reproductive toxicity studies, the 20

- week NOAELs ranged from 200 mg/kg

- diet (mallard, MRID 47832120, highest concentration tested) to 1000 mg/kg

- diet (bobwhite quail, highest concentrati on tested). No treatment

- related adverse effects were observed at any test treatment in these studies.

4.2.2 Toxicity to Mammals

In an acute oral ‘ up

- down ’ toxicity study conducted according to Organization for Economic Cooperation and Dev e lopment ( OECD ) protocol (MRID 47832144 ) , a series of fasted, young adult rats (6/sex) were given a single oral dose of sulfoxaflor XDE

- 208 in 0.5% aqueous methylcellulose at either 630 mg/kg bw (2 males, 2 females), 1000 mg/kg bw (2 males, 3 females), 1580 mg/kg bw (1 male, 1 female) or 2000 mg/kg bw (1 male). Based on an estimated
LD 50 of 1000 mg/kg bw, and an assumed standard deviation of 0.2, a starting dose level of 630 mg/kg bw of sulfoxaflor was administered to one male and one female rat. Since both animals69 su rvived, the second animals received a higher dose at 1000 mg/kg bw. Clinical signs included muscle tremors, twitches, tonoclonic convulsions, decreased activity, decreased reactivity

, decrease fec al output , eyelids partially closed (ptosis) , hair standi ng up (piloerection) , labored respiration, soiling, increased salivation, increased lacrimation, lack of coordination

, hypersensitivity to stimuli, , and decreased responsiv eness to touch. Mortality was observed at ≥1000 mg/kg bw. The male and female acute LD 50 values were estimated to be 1405 and 1000 mg/kg bw, respectively.

In an acute oral up

- down toxicity study conducted according to OECD guidelines (MRID 47832040), a se ries of fasted, young adult male mice were given a single oral dose of sulfoxaflor
95.6% TGAI n 0.5% aqueous methylcellulose at either 560 mg/kg bw (1 animal), 750 mg/kg bw (3 animals) or 1000 mg/kg bw (1 animal ). Clinical signs noted prior to death includ ed muscle twitches, tremors, and convulsions, increased reactivity to stimuli, and increased responsiveness to touch. No gross internal findings were observed at necropsy. The o ral LD 50 was determined to be 750 mg a.i./kg bw.

The acute, oral toxicity o f formulated products GF

- 2372 and GF

- 2032 was also evaluated with the rat at limit doses of 2000 and 5000 mg a.i./kg bw (MRID 47832505 and 47832407, respectively) . In both studies, no mortality or deleterious effects on body weight occurred at the
limit d oses. Rats exposed to GF

- 2372 showed sublethal effects including facial staining, ano

genital staining and/or reduced fecal volume ; all animals recovered with normal behavior at 8 days. No sublethal signs of toxicity were observed with rats administered 5000 mg a.i./kg bw
GF

- 2032.

In a chronic two

- generation dietary reproduction toxicity study, sulfoxaflor (95.6% purity) was
administered to Sprague Dawley rats (27/sex/dose group) at concentrations of 0, 25, 100 or 400 ppm in the diet for approximately ten weeks prior to breeding, and continuing through breeding, gestation and lactation for two generations. In

- life parameters included clinical observations, feed consumption, body weights, estrous cyclicity, reproductive performance, pup survival, pup
b ody weights, puberty onset and anogenital distance. In addition, post

- mortem evaluations included gross pathology and organ weights in weanlings, toxicokinetic analyses, gross pathology, organ weights, oocyte quantitation and sperm count, motility and morp hology, and histopathology, in adults. Systemic effects in parents consisted of only increased absolute and relative liver weights; these effects are not considered to be ecologically relevant and are not considered for the wild mammal risk assessment. Rep roductive effects were limited to 400 ppm and comprised slightly decreased neonatal survival in both generations (81.2 vs. 95.4% in controls) ; this in turn led to a lower percentage of live pups up to culling on post

- natal day 4 ( PND 4 ) . In addition, there was an apparent treatment

- related delay in preputial separation (PPS) for 400 ppm F 1 males. This external marker of male puberty onset is androgen dependent, but the underlying reason for how sulfoxaflor induced this finding is not known. There were no e ffects

on the onset of puberty or any other parameter of reproductive performance or offspring growth and survival at 25 or 100 ppm. Toxicokinetic data from lactation day 4 ( LD 4 ) dams and culled PND 4 pups in the second generation show dose

- proportional s ystemic exposure to sulfoxaflor in dams and their offspring. The LOAEL for reduced neonatal survival is 400 ppm (24.6 mg/kg/day) and the NOAEL is 1 00 ppm (6.07 mg/kg/day).70 4.2.3 Toxicity to Bees

Sulfoxaflor is considered highly toxic to the honeybee, Api s mellifera, with an acute contact
LD 50 value of 0.379 μ g ai/bee (TGAI; MRID 47832102) and 0.130 μ g ai/bee (formulated product GF

- 2032

- SC; MRID 47832419). Sulfoxaflor was also highly toxic on an acute oral basis ( LD 50 value of 0.146 μ g ai/bee (TGAI, MRID 47832103) and 0.052 μ g ai/bee (formulated product GF

- 2032

- SC, MRID 47832417). Conversely, the primary degradate (X474) is classified as practically nontoxic to bees on an acute contact basis with an acute contact LD 50 of >100 ug/bee (MRID 47832107). Base d on aged residues of GF

- 2032

- SC on alfalfa at 200 g/ha, <5% mortality occurred following exposure to alfalfa aged from 3 to 24 hours (MRID 47832420).
With the GF

- 2372

- WG formulation, up to 15% mortality occurred following exposure to alfalfa aged from 3

- 24 hours (MRID 47832512).

For the bumble bee, Bombus terrestris , sulfoxaflor (formulated product, GF

- 2032

- SC) was much less toxic compared to honeybee on an acute contact basis (LD 50 of 7.55 μ g ai/bee, MRID 47832418) compared to 0.130 μ g ai/bee for the ho neybee). However, based on acute oral exposure, the toxicity of sulfoxaflor formulated product (GF

- 2032

- SC) was similar among the bumble bee and honeybee ( 72

- h LD 50 of 0.027 μ g ai/bee; MRID 47832511 and 48

- h LD 50 of
0.052 μ g ai/bee, respectively).

4.2. 4 Toxicity to Terrestrial Plants

Sulfoxaflor did not exhibit treatment

- related signs of toxicity to terrestrial plants at or above the proposed maximum seasonal application rate on cotton (200 g/ha) based on vegetative vigor and seedling emergence tests ( MRID 47832425 and 47832427, respectively).71 

### 5. **R ISK**  

### C **HARACTERIZATION**

Risk characterization provides the final step in the risk assessment process. In this step, exposure and effects cha racterization are integrated to provide an estimate of risk relative to established levels of concern (LOCs; Section 5.1 ). The results are then interpreted for the risk manager through a risk description and synthesized into an overall conclusion ( Section 5.2 ). In addition, the risk description also contains a discussion of relevant sources of uncertainty in the risk assessment and sensitivity of the risk assessment findings to important methodological assumptions.

5.1 Risk Estimation

- Integration of E xposure and Effects Data

As discussed in the problem formulation, r isk characterization integrates EECs and toxicity estimates and evaluates the likelihood of adverse ecologica l effects to non

- target species. For

su l foxaflor , a deterministic approach is used to evaluate the likelihood of adverse ecological
effects to non

- target species. In this approach, RQs are calculated by dividing EECs by acute and chronic ecotoxicity valu es for non

- target species.

Risk Quotient (RQ) = Exposure Estimate/Toxicity Estimate

RQs are then compared to LOCs. These LOCs are criteria used to indicate potential risk to non

target organisms and the need to consider regulatory action. LOC exceede nce is interpreted to mean that the labeled use (or proposed use) of the pesticide has the potential to cause adverse
effects on non

- target organisms. LOCs currently address the following risk presumption categories:

Animals :

• acute risk

- potential for acute risk to non

- target organisms which may warrant regulatory action in addition to restricted use classification,

• acute risk, restricted use

– potential for acute risk to non

- target organisms, but may be mitigated through restricted use classification,

• acute risk, listed species

– listed species may be potentially affected by use,

• chronic risk

– potential for chronic risk may warrant regulatory action, listed species may potentially be affected through chronic exposure,
Plants

• non - listed plant risk

- po tential for effects in non

- target (non

- endangered) plants, and

• listed plant risk

– potential for effects in endangered plants.

Risk presumptions, along with the calculation of the corresponding RQs and LOCs, are tabulated
below:72 Table 24

. Risk Presumptions for Aquatic Animals

Risk Presumption RQ LOC

Acute Risk EEC/LC 50 or EC 50 0.5

Acute Restricted Use EEC/LC 50 or EC 50 0.1

Acute Endangered Species EEC/LC 50 or EC 50 0.05

Chronic Risk EEC/NOAEC 1

Table 25

. Risk Presumptions for Terrestrial Vertebrate Animals

Risk Presumption RQ LOC

Acute Risk Diet

- based EEC/LC 50 or Dose

- based EEC/LD 50 0.5

Acute Restricted Use Diet

- based EEC/LC 50 or Dose

- based EEC/LD 50 (or LD 50 < 50 mg/kg) 0.2

Acute Endangered S pecies Diet

- based EEC/LC 50 or Dose

- based EEC/LD 50 0.1

Chronic Risk Diet or Dose

- based EEC/Diet or Dose

- based NOAEC 1

Table 26

. Risk Presumptions for Terrestrial Invertebrate Animals

Risk Presumption RQ LOC

Acute Risk to Bees (1) EEC (adult contact) / LD 50 (adult contact)
EEC (adult or larvae oral) / LD 50 (adult or larvae oral) 0.4

Chronic Risk to Bees (1) EEC (adult or larvae oral) / NOAEC or LD10 (adult or larvae) 1

(1) RQ and LOC values for bees are proposed values (USEPA 20 12)

.

Table 27

. Risk Presumptions for Plants

Risk Presumption RQ LOC

Terrestrial Plants in Terrestrial and Semi

- Aquatic Areas:

Non

- Endangered Species EEC (1) /EC 25 1

Endangered Species EEC/EC 05 or NOAEC 1

Aquatic Plants:

Non

- End angered Species EEC (2) /EC 50 1

Endangered Species EEC/EC 05 or NOAEC 1

5.1.1. Risks to Non

- Target Aquatic Animals

Acute and chronic risks to aquatic animals are first estimated based on the maximum aquatic
EEC s determined from all 51 crop exposure scen arios modeled combined with the most sensitive endpoint within each taxonomic group, as identified in Table 22

. For screening purposes, this initial comparison is based on the total residues of interest (parent +X

- 474+X

- 540). If the maximum RQ value did not exceed the applicable LOC, then no further risk estimation was
conducted and a low potential for risk was presumed . If maximum RQ value exceeded the acute73 or chronic risk LOC, then RQ values re

- calculated usin g the refined EECs with parent and X

- 540 constituents, which are considered the residues of toxicological concern.

5.1.1. 1. Fish and Invertebrates: Water Column Exposure

Sulfoxaflor is classified as practically non

- toxic to freshwater and saltwater fis h on an acute exposure basis. As a result, maximum acute and chronic RQ values for freshwater and saltwater
fish determined with the crop exposure scenario producing the highest aquatic EECs ( NC
Cotton ) are one to three orders of magnitude below the liste d and non

- listed species LOC values
of 0.5 and 0.05

, respectively ( Table 28 ).

Table 28

. Maximum acute and chronic risk quotients for freshwater and saltwater fish
based on total residues of interest

Use Category Crop
Scenario Peak EEC 1 (mg/L) 60

- day

EEC 1 (mg/L) Acute RQ 2 Chronic RQ 3

FW SW FW SW

Cotton NC Cotton 0.0530 0.0527 <0.0001 0.0002 0.08 0.04

1 For screening purposes, these EECs are based on total residues of interest (parent + X

- 474 + X

- 540 )

. 2 Acute RQ values for freshwater and saltwater fish are based on the peak EEC / LC 50 values of >363 mg a.i./L ( bluegill sunfish ) and 266 mg a.i./L (sheepshead minnow), respectively (see Table 22 )

3 Chronic RQ values for freshwater and saltwater fish are based on the 60

- d average EEC / NOAEC values of 0.66

mg a.i./L (fathead minnow) and 1.2 mg a.i./L (sheepshead minnow), respectively (see Table 22 )

Maximu m acute RQ values for freshwater invertebrates are three orders of magnitude below the
acute risk to listed species LOC while that for saltwater invertebrates marginally exceeds (RQ=0.08) the acute risk to listed species LOC of 0.05 ( Table 29 ). Maximum chronic RQ values do not exceed the chronic risk LOC (1.0) for either freshwater or saltwater invertebrates.

Table 29

. Maximum acute and chronic risk quotients for freshwater and saltwater
I nvertebrates based on total residues of interest

Use Category Crop
Scenario Peak EEC (mg/L) 21

- day

EEC (mg/L) Acute RQ 2 Chronic RQ 3

FW SW FW SW

Cotton NC Cotton 0.053 0.0529 <0.0001 0.08 4 0.001 0.5

1 For screening purposes, these EECs are based o n total residues of interest (parent + X

- 474 + X

- 540 )

. 2 Acute RQ values for freshwater and saltwater invertebrates are based on the peak EEC / LC 50 values of >400 mg a.i./L ( Daphnia magna ) and 0.64 mg a.i./L (mysid shrimp), respectively (see Table 22 )

3 Chronic RQ values for freshwater and saltwater invertebrates are based on the 21

- d average EEC / NOAEC
values of 50.5 mg a.i./L ( D

. magna ) and 0.11 mg a.i./L ( mysid shrimp ), respectively (see Table 22

. )

4 Bolded value exceeds acute risk to listed species LOC of 0.05.

Since the maximum acute RQ for saltwater invertebrates exceeds the acute risk to listed species
LOC based on total re sidues of interest , acute RQ values were re

- calculated with refined EECs that include only the toxicological residues of concern (parent + X

- 540) for those exposure scenarios with RQs that exceed the LOC. These refined RQ values are shown in Table 30 and
are well below LOCs for non

- listed and listed species

.74 Table 30

. Acut e risk quotients for saltwater i nvertebrates using refined EECs based on
total toxic residues of concern

Crop (State) Crop(s) Scenario EEC Total (ug ai/L) 1 Acute RQ 2
,

Beans (MI) Beans (dry & Lima, snab) MIbeansSTD 5.5 0.009
Citrus (FL) Citrus FLcitrusSTD 4.9 0.008

Cotton (NC) Cotton NCcottonSTD 4.6 0.007

Cotton (MS) Cotton MScottonSTD 4.6 0.007

Vegetables: Brassic a (cole) Leafy Broccoli, Brussels sprouts, Cabbage, Cauliflower, Kale FLcabbageSTD 1.1 0.002

Vegetables: Bulb (GA) Onion (dry/green) &
Pearl GAOnion_WirrigSTD 3.1 0.005 Vegetables: Leafy except Brassica Lettuce/Celery/ Spinach CAlettuceSTD 1.7 0.003 Veg etables: Root &
tuber Potatoes, Turnip& Rutabaga MEpotatoSTD 2.5 0.004 Vegetables: Root &
tuber Sweet Potatoes NCs weetpotatoSTD 4.2 0.007

1 EECs are based on total toxic residues of concern (parent + X

- 540; see Ta ble 17 )

. 2 Acute RQ values for saltwater invertebrates are based on the peak EEC / LC 50 values of 0.64 mg a.i./L (mysid shrimp ; see Table 22 )

.

5.1. 1. 2

. Aquatic Invertebrates: Sediment Exposure

Risk quotients for freshwater and saltwater benthic invertebrates using the crop exposure scenario with the highest acute and chronic EEC in sediment porewater (NC cotton) are provided
in Table 31 . For estimating acute risks to benthic invertebrates, risk quotients were determined using peak porewater EECs (reported in Table 18 ) divided by the lowest acute toxicity endpoi nt for fresh and saltwater water column invertebrates, since acute toxicity data were not available from sediment toxicity studies. For estimating chronic risks to benthic invertebrates, risk quotients were determined by dividing the highest 21

- d average EEC in pore water by the lowest pore water NOAEC obtained for the midge (freshwater) and water column exposure NOAEC for mysid shrimp. As the pore water EECs were nearly identical to the water column EECs, RQ
values based on water column toxicity data (ac ute FW & SW, chronic SW) are identical to those
described earlier in Table 29 . For fresh water benthic invertebrates, a slight exceed a nce (RQ=0.08 ) of the acute risk to listed species LOC and the chronic risk (RQ= 1.4) LOC is
indicated

.75 Table 31

. Maximum acute and chronic risk quotients for fr eshwater and saltwater benthic
i nvertebrates based on total residues of interest

Use Category Crop
Scenario Peak Pore

Water EEC 1 (mg/L) 21

- day Pore

Water EEC 1 (mg/L) Acute RQ 2 , 3 Chronic RQ 3
, 4

FW SW FW SW

Cotton NC Cotton 0.051 0.050 <0. 00 01 0.08 1. 4 0.5

1 For screening purposes, these EECs are based on total residues of interest (parent + X

- 474 + X

- 540).

2 Acute RQ values for benthic fres hwater and saltwater invertebrates are based on the peak pore water EEC /

E C 50 values of >400 mg ai/L ( Daphnia magna ) and an LC 50 value of 0.64 mg ai/L (mysid shrimp), respectively (see Table 22 )

3 Chronic RQ value s for freshwater and saltwater benthic invertebrates are based on the 21

- d average pore

water EEC / 28

- d NOAEC values of 0.0 37 mg ai/L

- pore water ( Chironomus riparius) and 0.11 mg ai/L ( mysid shrimp ), respectively (see Table 22 )

3 Bolded value exceeds acute risk to listed species LOC of 0.05

4 Bolded value exceeds chronic risk to listed species LOC of 1.0

Since the maximum acute RQ for saltwater benthic invertebrates using the total residues of
interest exceeds th e acute risk to listed species LOC and the maximum chronic RQ for
freshwater benthic invertebrates the chronic risk LOC, acute and chronic RQ values were for those scenarios exceeding the LOCs were re

- calculated using just the residues of toxicological

con cern (parent and X

- 540). Those RQ values that exceeded the acute risk to listed species
LOC s and chronic risk LOC s are provided in Table 32

. These refined RQ values are well below
acute and chronic risk LOCs for n on

- listed and listed species

.

Table 32

. Risk quotients for benthic Invertebrates using refined EECs based on total toxic
residues of concern

Crop (State) Crop(s) Scenario Peak Pore

Water EEC (mg ai/L) SW

Acute
RQ 1 21

- d Avg. Pore

Water EEC (mg ai/L) FW
Chronic

RQ 2

Beans (MI) Beans (dry & Lima, snab) MIbeansSTD 4.06 0.006 4.06 0.11

Citrus (FL) Citrus FLcitrusSTD 2.67 0.004 2.67 0.07

Cotton (NC) Cotton NCcottonSTD 3.37 0.005 3.32 0.09

Cotton (MS) Cotton MScottonSTD 3.40 0.005 3 .35 0.09 Vegetables: Brassica (cole) Leafy Broccoli, Brussels sprouts, Cabbage, Cauliflower, Kale FLcabbageSTD 0.65 0.001 0.65 0.02 Vegetables: Bulb (GA) Onion (dry/green)
& Pearl GAOnion_Wirr igSTD 2.02 0.003 2.02 0.05 Vegetables: Leafy except
Brassica Lettuce/Celery/ Spinach CAlettuceSTD 1.33 0.002 1.33 0.04 Vegetables: Root
& tuber Potatoes, Turnip& Rutabaga MEpotatoSTD 2.48 0.004 2.47 0.07 Vegetables: Root
& tuber Sweet Potatoes NC s weetpotato STD 3.21 0.005 3.21 0.0976 Crop (State) Crop(s) Scenario Peak Pore

Water EEC (mg ai/L) SW

Acute
RQ 1 21

- d Avg. Pore

Water EEC (mg ai/L) FW
Chronic

RQ 2

1 Acute RQ values for benthic sa ltwater invertebrates are based on the peak pore water EEC / LC 50 value 0.64 mg ai/L (mysid shrimp; see Table 22 )

2 Chronic RQ values for freshwater benthic invertebrates are based on the 21

- d average pore water EE C / 28

- d
NOAEC values of 0.0 37 mg ai/L

- pore water ( Chironomus riparius ; see Table 22 )

5.1. 2 Risks to Aquatic Plants

Risk quotients calculated for vascular and non

- vascular aquatic plants using the crop exposure scenario with the highest acute and chronic EEC s in surface water (NC cotton) are provided
Table 33

. None of the risk quotients exceed the LOC for listed or non

- listed aquatic plant species.

Table 33

. Maximum acute and chronic risk quotients for non

- vascular and vascular aquatic plants

Use Category Crop
Scenario Peak EEC (mg/L) 1 Non

- Vascular Plant RQ 2 Vascular Plant RQ 3

Non

- Listed Listed Non

- Listed Lis ted

Cotton NC Cotton 0.0530 < 0.0007 0.02 <0.0005 0.0005

1 For screening purposes, these EECs are based on total residues of interest (parent + X

- 474 + X

- 540).

2 R Q values for non

- listed and listed non

- vascular aquatic plants are based on the peak surface water EEC /

EC 50 value of >95.6 mg ai/L and a 96

- h NOAEC of 3.54 mg ai/L, respectively ( f reshwater diatom, Navicula pelliculosa ; see Table 22 )

3 RQ values for non

- listed and listed vascular aquatic plants are base d on the peak surface water EEC / 7

- d EC 50 value of >99 mg ai/L and a 7

- d NOAEC of 99 mg ai/L, respectively ( Duckweed (Lemna gibba; see Table 22 )

5.1. 3 Risks to Terres trial Animals

Potential risks to mammals and birds are derived using T

- REX (version 1.5) with biological inputs including: 1) acute and chronic toxicity data for the rat and mallard, 2) weights of three

mam malian and avian size classes, and 3) various dietary categories being consumed. Chemical

specific inputs include: 1) application rate, 2) application interval, 3) frequency of applications,
and a chemical

- specific foliar dissipation rate of 12.3 days.

For sulfoxaflor, the proposed use pattern encompasses four different modeling scenarios for T

REX:

• 2 x 0.133 lb ai/A @ 7 d interval ( citrus, fruits

- pome, fruits

- stone, ornamentals, tree nuts, turf grass )

• 3 x 0.090 lb ai/A @ 7 d interval ( beans, berries, s oybeans, veg.

- brassica, veg.

- bulb,

veg.

- leafy, veg.

- root/tuber, veg.

- fruiting, veg.

- cucurbit, watercress )

• 3 x 0.090 lb ai/A @ 5 d interval ( cotton ) , and

• 2 x 0.043 lb ai/A @ 14

- d intervals ( canola and grains )77 Of these exposure scenarios, the first (2 x 0.1 33 lb ai/A @ 7 d interval) yields the highest residues on terrestrial forage items. Therefore, it is used here as an initial screen for evaluating whether the proposed uses of sulfoxaflor have potential risks to avian and mammalian wildlife.

5.1. 3 .1

. Ac ute Risk to Mammals

Acute mammalian RQ values are calculated using the rat acute oral toxicity data (LD 50 =1000 mg/kg b

. w

. ) adjusted for differences in body weight for a small (15g), me dium (35g) and large (1000g) mammal by T

- REX (adjusted LD 50 =2198, 1778, and 769 mg/kg b.w., respectively) and
the modeled acute dose

- based EECs for various use scenarios and diet categories. Results f rom the application scenario providing the highest res idues on forage items (Citrus, Fruits

- Pome,
Fruits

- Stone, Ornamentals, Tree nuts, Turf grass) are provided in Table 34

. These results are
based on the 90 th percentile foliar dissipation half life of 12.3 days for sulfoxaflor. Maximum acute mammalian RQ values are all below 0.1 which indicates a low acute risk potential to listed
and non

- listed mammals consuming the modeled forage items.

Table 34

. Maximum acute dose

- based risk quotients fo r mammals

Size
Class (g) Adjusted

LD 50 (mg/kg

bw) EECs (mg a.i./kg bw) and RQs 1 ,2

Short Grass Tall Grass Broadleaf Plants Fruits/Pods/

Seeds Arthropods Granivore

EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ 2 x 0.133 lb ai/A, 7 d Interval (Citrus, Fru its

- Pome, Fruits

- Stone, Ornamentals, Tree nuts, Turf grass

15 2198 5 1.0 0.02 23. 2 0.01 28. 7 0.01 3. 2 0.00 20.0 < 0.0 1 0.7 1 <0.01

35 1778 35.2 0.02 16.1 0.01 19.8 0.01 2.2 0.00 13.8 <0.01 0.4 9 <0.01

1000 769 8. 2 0.01 3.7 < 0.00 4. 6 0.01 0.5 0.00 3. 2 <0.01 0.11 <0.01

1 EECs calculated using T

- REX based on sulfoxaflor

- specific foliar dissipation half life of 12.3 days.

2 Acute RQ values calculated as EEC/ size class

- adjusted LD50 based on unadjusted LD50 of 1000 mg a.i./kg bw for the rat (MRID

47832144 ).

5. 1. 3 .2

. Chronic Risks to Mammals

Potential chronic risks to mammals are derived using a dietary

- based NOAEL of 100 ppm from a
2

- generation reproduction study with the rat (MRID 47832142 ) and EECs for the crop exposure scenario yielding the maximum residues on forage items (2 x 0.133 lb ai/A ). The chronic dietary

based RQ values range from 0.03 (Fruits, po ds, seeds, large insects) to 0.5 (short grass). Since
these chronic RQ values are al l below the chronic risk LOC of 1.0, the potential for chronic risks to mammals is based on a dietary approach is considered low ( Table 35 ).78 Table 35

. Maximum chronic diet

- based risk quotie nts for mammals

NOAEC (ppm in
diet ) EECs (ppm diet) and RQs 1,2

Short Grass Tall Grass Broadleaf
Plants Fruits/Pods/Seeds /Large Insects Arthropods

EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ 2 x 0.133 lb ai/A, 7 d Interval (Citrus, Fruits

- Pome, Fruits

- Stone, Ornamentals, Tree nuts, Turf grass )

100 53.4 0.53 24.5 0.24 30.1 0.30 3.3 0.03 20.9 0.21

1 EECs calculated using T

- REX based on sulfoxaflor

- specific foliar dissipation half life of 12.3 days.

2 Chronic RQ values calculated based on the dietary EEC / NOA EC of 100 ppm in the diet (MRID 47832142

Potential chronic risks to mammals are also evaluated using a dose

- based approach which relies

on a NOAEL of 6.07 mg a.i./kg bw/d from the same 2

- generation toxicity rat study (MRID
47832142 ). This dose

- based NOA EL is adjusted in the T

- REX model to account for different
size classes of mammals . Specifically, body

- weight adjusted NOAELs of 13.3, 10.8, and 4.7

mg a.i./kg b w /d were calculated 15g, 35g and 1000g mammals, respectively. These adjusted
values are used to interpret the dose

- based EECs calculated for the same mammalian size
classes

. The overall range in chronic RQ values is from 0.01 to 3.8 , and t he potential for chronic risks to mammals is identified for all crop scenarios for at least one dietary cate gory ( Table 36 )

.

Table 36

. Chronic dose

- based RQ values for mammals

Size
Class (g) Adjusted NOAEL (mg a.i./kg bw/d) EECs (mg a.i./kg bw/d) and RQs 1,2

Short Grass Tall Grass Broadleaf P lants Fruits/Pods/

Seeds Arthropods Granivore

EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ 2 x 0.133 lb ai/A, 7 d Interval (Citrus, Fruits

- Pome, Fruits

- Stone, Ornamentals, Tree nuts, Turf grass

15 13.3 50.9 3.8 23.4 1.8 28.7 2.1 3.2 0.24 20.0 1.5 0.71 0 .05

35 10.8 35.2 3.3 16.1 1.5 19.8 1.8 2.2 0.20 13.8 1.3 0.49 0.05

1000 4.7 8.2 1.7 3.7 0.80 4.6 0.98 0.51 0.11 3.2 0.68 0.11 0.02 3 x 0.090 lb ai/A, 7 d Interval (Beans, Berries, Soybeans, Veg.

- Brassica, Veg.

- Bulb, Veg.

- Leafy, Veg.

- Root/Tuber, Veg.

- Fr uiting, Veg.

- Cucurbit, Watercress)

15 13.3 47.9 3.6 21.9 1.6 26.9 2.0 3.0 0.22 18.7 1.4 0.66 0.05

35 10.8 33.1 3.1 15.2 1.4 18.6 1.7 2.1 0.19 13.0 1.2 0.46 0.04

1000 4.7 7.7 1.6 3.5 0.75 4.31 0.92 0.48 0.10 3.0 0.64 0.11 0.02 3 x 0.090 lb ai/A, 5 d Int erval (Cotton)

15 13.3 53.4 4.0 24.5 1.8 30.0 2.3 3.3 0.25 20.9 1.6 0.74 0.06

35 10.8 36.9 3.4 16.9 1.6 20.8 1.9 2.3 0.21 14.5 1.3 0.51 0.05

1000 4.7 8.6 1.8 3.9 0.84 4.8 1.0 0.53 0.11 3.4 0.72 0.12 0.03 2 x 0.043 lb ai/A, 14

- d Intervals (Canola, Gr ains)

15 13.3 14.3 1.1 6.6 0.49 8.0 0.60 0.89 0.07 5.6 0.42 0.20 0.01

35 10.8 9.9 0.92 4.5 0.42 5.6 0.52 0.62 0.06 3.9 0.36 0.14 0.01

1000 4.7 2.3 0.49 1.1 0.23 1.3 0.28 0.14 0.03 0.90 0.19 0.03 0.0179 Size
Class (g) Adjusted NOAEL (mg a.i./kg bw/d) EECs (mg a.i./kg bw/d) and RQs 1,2

Short Grass Tall Grass Broadleaf P lants Fruits/Pods/

Seeds Arthropods Granivore

EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ

1 EECs calculated using T

- REX based on sulfoxaflor

- s pecific foliar dissipation half life of 12.3 days.

2 Chronic dose

- based RQ values calculated as dietary EEC / size class

- adjusted NOAEC based on an unadjusted NOAEC of 6.7 mg/kg bw/d (MRID 47832142 ) RQ values shown in bold exceed the chronic risk LOC of 1. 0

5.1. 3 .3

. Acute Risk to Birds

For sulfoxaflor, avian dose

- based acute RQs are based on the zebra finch acute oral toxicity data (LD 50 > 80 mg a.i./kg bw ; MRID 47832072 ) which ref lects the concentration above which dose

dependent effects of regurgitation were observed. Thus, a value of 80 mg a.i./kg bw is used as a
conservative screen for acute risks to birds. Acute dose

- based RQ values are based on LD 50 values adjusted differenc es in body weight for birds (20, 100, 1000g) (adjusted LD 50 =86.4, 110 and 155 mg a.i./kg bw, respectively) and modeled acute dose

- based EECs for various use scenarios and diet categories and a sulfoxaflor

- specific foliar DT 50 of 12.3 days.

Avian acut e RQs for sulfoxaflor are shown in Table 37

. The overall range in acute RQ values is
from < 0.01 to 0.7 0 , and the potential for acute risks to birds (including reptiles and terrestrial

phase amphibians) is identifie d for all crop scenarios for at least one dietary category

Table 37

. Acute dose

- based risk quotients for birds

Size
Class (g) Adjusted

LD 50 (mg a.i./kg

bw) EECs (mg a.i./kg

- bw) and RQs*

Short Grass Tall Grass Broadleaf
Plants Fr uits/Pods/Seeds Arthropods Granivore

EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ 2 x 0.133 lb ai/A, 7 d Interval (Citrus, Fruits

- Pome, Fruits

- Stone, Ornamentals, Tree nuts, Turf grass

20 86.4 60.9 < 0.70 27.9 < 0.32 34.2 < 0.40 3.8 < 0.04 23.8 < 0.28 0.85 < 0.01

100 110 34.7 < 0.32 15.9 < 0.14 19.5 < 0.18 2.2 < 0.02 13.6 < 0.12 0.48 < 0.00

1000 155 15.5 < 0.10 7.1 < 0.05 8.7 < 0.06 0.97 < 0.01 6.1 < 0.04 0.22 < 0.00 3 x 0.090 lb ai/A, 7 d Interval (Beans, Berries, Soybeans, Veg.

- Brassica, Veg.

- Bulb, Veg.

- Leafy, Veg.

- Root/Tuber, Veg.

- Fruiting, Veg.

- Cucurbit, Watercress)

20 86.4 57.2 < 0.66 26.2 < 0.30 32.2 < 0.37 3.6 < 0.04 22.4 < 0.26 0.79 < 0.01

100 110 32.6 < 0.30 14.9 < 0.14 18.3 < 0.17 2.0 < 0.02 12.8 < 0.12 0.45 <0.01

1000 155 14.6 < 0.09 6.7 < 0.04 8.2 < 0.05 0.91 < 0.01 5. 7 < 0.04 0.20 <0.01
3 x 0.090 lb ai/A, 5 d Interval (Cotton)

20 86.4 63.8 < 0.74 29.2 < 0.34 35.9 < 0.42 4.0 < 0.05 25.0 < 0.29 0.89 < 0.01

100 110 36.4 < 0.33 16.7 < 0.15 20.5 < 0.19 2.3 < 0.02 14.2 < 0.13 0.51 <0.01

1000 155 16.3 < 0.10 7.5 < 0.05 9.2 < 0.06 1.0 < 0.01 6.4 < 0.04 0.23 <0.01
2 x 0.043 lb ai/A, 14

- d Intervals (Canola, Grains)80 Size
Class (g) Adjusted

LD 50 (mg a.i./kg

bw) EECs (mg a.i./kg

- bw) and RQs*

Short Grass Tall Grass Broadleaf
Plants Fr uits/Pods/Seeds Arthropods Granivore

EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ

20 86.4 17.1 < 0.20 7.8 < 0.09 9.6 < 0.11 1.1 < 0.01 6.7 < 0.08 0.24 < 0.0 1

100 110 9.7 < 0.09 4.5 < 0.04 5.5 < 0.05 0.61 < 0.01 3.8 < 0.03 0.14 < 0.0 1

1000 155 4.4 < 0.03 2.0 < 0.01 2.5 < 0.02 0.27 < 0.00 1.7 < 0.01 0.06 < 0.0 1

1 EECs calculated using T

- REX based on sulfoxaflor

- specific foliar dissipation half life of 12.3 days.

2 Acute RQ values calculated as EEC/size class

- adjusted LD50 based on unadjusted LD50 of 80 mg a.i./kg bw for the z ebra finch (MRID

47832072 ) RQ values shown in bold exceed the acute risk to listed species LOC of 0.1

Avian subacute diet ary

- based acute risk quotients for the crop scenario resulting in the maximum residues on forage items are provided in Table 38

. These RQ values are based on the dietary
LC 50 of 5,620 ppm diet for the mallard duck (MRID 47832104 ) and a sulfoxaflor

- specific foliar dissipation half life of 12. 3 days

. No subacute acute risk is identified with the dietary

- based approach, as RQ values are all well below the acute risk to listed species LOC of 0.1.

Table 38

. Maximum acute diet

- based risk quotients for birds

LC 50 (ppm diet) EECs (ppm in diet) and RQs 1,2

Short Grass Tall Gras s Broadleaf
Plants Fruits/Pods/Seeds Arthropods

EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ 2 x 0.133 lb ai/A, 7 d Interval (Citrus, Fruits

- Pome, Fruits

- Stone, Ornamentals, Tree nuts, Turf grass

5620 53.44 0.01 24.49 < 0.0 1 30.06 0.01 3.34 < 0.0 1 20.93 < 0.0 1

1 EECs calculated using T

- REX based on sulfoxaflor

- specific foliar dissipation half life of 12.3 days.

2 Acute RQ values calculated as EEC/subacute LC50 of 5,620 ppm diet for mallard (MRID 47832104 )

Potential chronic effects to terrestrial birds (includin g reptiles and terrestrial

- phase amphibians) are derived by considering highest dietary

- based EECs modeled in T

- REX for a bird consuming a variety of dietary items. Chronic effects are estimated using the lowest available chronic dietary toxicity data for birds (NOAEC= 200 mg/kg

- diet for mallard duck) and a sulfoxaflor

specific foliar dissipation half life of 12.3 days . Chronic dietary

- based RQs range from 0.02 to
0. 27 ( Table 39 ) , thus indicating a low potential for chronic risks to birds

.

Table 39

. Maximum chronic diet

- based risk quotients for birds

NOAEC (ppm) EECs and RQs 1 , 2

Short Grass Tall Grass Broadleaf
Plants Fruits/Pods/Seeds Arthropods

EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ

2 x 0 .133 lb ai/A, 7 d Interval (Citrus, Fruits

- Pome, Fruits

- Stone, Ornamentals, Tree nuts, Turf grass

200 53.44 0.27 24.49 0.12 30.06 0.15 3.34 0.02 20.93 0.10

1 EECs calculated using T

- REX based on sulfoxaflor

- specific foliar dissipation half life of 12.3 days.

2 Chronic RQ values calculated as EEC/ dietary NOAEC of 100 ppm diet for the rat (MRID 47832142 )81 5.1. 3 .4

. Non

- target Terrestrial and Semi

- Aquatic Plants

For sulfoxaflor, the NOAEC values from seedling emergence and vegetative vigor toxicity tests of terrestrial plants are above the maximum single application rate of 0.133 lb ai/A (MRID
47832425 and 47832427 ) . Therefore, a low potential for risk to listed and non

- listed terrestri al plants is expected based on the proposed use profile for sulfoxaflor.

5.1.3

. 5

. Risk Estimation for Bees

Figure 15 illustrates the proposed decision

- making process for assessing risks to honey bees
associate d with foliar spray applications of pesticides ( e.g ., via ground and aerial methods) including systemic pesticides such as sulfoxaflor. Th is decision

- making framework was recently presented and reviewed by a FIFRA Scientific Advisory Panel

. 17 The overall p roposed approach is a tiered process whereby risks are first assessed using simple and conservative exposure screening models to generate estimated environmental concentrations (EECs) ( Boxes 3a

, 3b and
3c of Figure 15 ) coupled with toxicity estimates derived from laboratory studies (Tier I) to calculate risk quotients (RQs) ( Boxes 4a

, 4b and 4c ). Results from the Tier I risk assessment process are expected to be reasonably c onservative such that the likelihood of a false negative is low ( i.e ., the chance that no risk is indicated but risks actually occur), while at the same time ensuring that the likelihood of a false positive ( i.e ., the chance that risk is indicated when non e actually exists) is not unacceptably high. For example, the initial exposure estimates used in Tier I are generally not chemical

- specific, but rather reflect upper

- bound estimates that would encompass exposures across all relevant pesticide uses. If ris ks are identified in Tier I ( i.e

., where risk estimates exceed levels of concern 18 ; Box 5 ), additional data may be used to refine the results, such as using estimates of exposure derived from available magnitude of residue or other commonly submitted studie s ( Box 6 )

.

If risks are still identified after refinement with available data ( Box 7 ), then appropriate risk mitigation options would be identified and further evaluated for their impact on risk estimates ( Box 8 ). Alternatively (or in addition), a higher t ier assessment may be necessary (Tier II) and studies providing refined estimates of exposure ( e.g ., field studies quantifying residues in pollen and nectar; Box 9a ) and effects at the colony level ( e.g ., semi

- field tunnel studies or field

- level feeding st udies; Box 9b ) may be requested. Measured residues in pollen and nectar ( Box 9a ) from these studies may be used to refine risk estimates from Tier I ( Box 6 ) and/or for qualitatively evaluating risk at the colony level associated with pesticide applications ( Box 10 ). They may also be used to identify more targeted risk mitigation options than those that could be
identified based on Tier I risk estimates.

Although not specifically depicted in Figure 15 for foliar appl ications, data from the toxicity of residues on foliage study are used qualitatively to characterize the length of time that residues

17 http://www.epa.gov/scipoly/sap/meetings/2012/091112meeting.html )

. 18 As described in USEPA (2012), an acute risk level of concern of 0.4 is proposed for the honey bee.82 remain toxic to bees. The results of the guideline study may result in precautionary label
statements similar to those dis cussed in the EPA Label Review Manual (USEPA 2012) or in guidance documents intended to reduce the potential effects of pesticides on bees ( e.g ., Riedl et al . 2006).

If available risk mitigation options ( Box 11 ) do not provide for an acceptable reduction i n risk, proceeding to Tier III ( Box 12 ) may be necessary to resolve specific uncertainties identified from Tiers I and II for the proposed uses of the pesticide. For example, effects on the ability of colonies to successfully emerge in the spring ( e

. g ., pr oduce sufficient brood and adult bees after

over

- wintering) may be a concern for some pesticides/uses which are not typically addressed in
earlier tiers.

The risk assessment process depicted in Figure 15 is inten ded to be iterative and to rely on multiple lines of evidence to further refine and characterize potential risk. At a screening level, risk to individual bees is quantified through the use of RQ values. Where RQ values exceed the LOC, more refined estimate s of exposure may be used to re

- evaluate RQ values for individual bees based on laboratory toxicity estimates. Where RQs still exceed LOCs, higher tier semi

- field
and full

- field studies may be required to determine whether effects observed under highly

con trolled conditions extend to the whole colony under increasingly realistic exposure
conditions.

As depicted in Figure 15 , if the multiple lines of evidence indicate that unacceptable effects on survival, growth o r reproduction of the colony are not likely, then a presumption of minimal risk can be supported. Alternatively, there may be situations where colony

- level effects may be likely, given the proposed use or known mode of action of a compound. In this case, a presumption of minimal risk cannot be supported, and risk assessors should attempt to characterize the nature and possible magnitude and duration of the effect. This characterization
should include a discussion of uncertainties which limit the extent to w hich the possible magnitude and duration can be estimated. Also, the risk characterization should include any potential mitigation options for minimizing risk to bees from the proposed use of a pesticide.83 Figure 15

. Proposed Tier ed Approach for Assessing Risk to Honey Bees from Foliar Spray Applications84 a) Tier 1 Risk Estimation for Honey Bees

For the initial Tier 1 screen, two exposure routes are considered : dietary and contact. Table 40 summarizes the initial residue values expressed in units of μ g a.i./bee per 1 lb a.i./A

. As discussed below, these values are adjusted to account for the application rate of the chemical. For generating RQs, dietary based exposure values are compared to or al toxicity data for larvae and adult worker bees while contact exposure values are compared to acute contact toxicity data for
adult worker bees.

As indicated in Table 40 , the initial screening

- level RQs exceed the proposed LOC of 0.4 for adults (oral and contact) exposures. Therefore, additional refinement of the Tier 1 exposure
estimates is warranted.

Table 40

. Tier I exposure values of honey bees to pesticides applied via foliar appl ications

Life Stage Exposure Type Dose ( μ g a.i./bee per 1 lb a.i./A) (1) Sulfoxaflor Dose for Max Application

Rate ( μ g a.i./bee per 0.133 lb a.i./A) Acute RQ) (2 ) ( 3 ) Chronic RQ) ( 3)

Adult Diet (nectar + pollen) 32 4.3 83 n.a.

Adult Direct contact 2.7 0.7 2 2.8 n.a. ( 1) Source: USEPA 2012. Draft Pollinator Risk Assessment Framework
(2) Based on a 48

- h acute oral LD 50 of 0.0515 ug ai/bee for GF

- 2032 ( MRID 47832417) and acute contact
LD 50 of 0.130 ug ai/bee for GF

- 2032 (MRID 47832419).
( 3 ) Bolded value excee ds the acute risk LOC of 0.4

b) Refined Tier 1 Risk Estimation for Honey Bees

Sulfoxaflor Residue Studies

As indicated in Box 6 of Figure 15

, refinements of Tier 1 risk estimation for oral exposure can be accomp lished by using chemical

- specific data on residues in pollen and nectar. For sulfoxaflor, such residue data are available from multiple studies including a field residue study with cotton (MRID 48755606), pumpkin (MRID 48755601) and Phacelia (MRID 4844660 1 and 48445806). Maximum reported residues in various plant and hive matrices are shown in Table
41

. Details of these studies are provided in Appendix D

.

Table 41

. Maximum reported residues (ppm) of sulfoxaflor in plant and hive mater ials
from various field studies

Application Rate (lb ai/A) Plant
Pollen * Plant

Nectar Plant

Tissue Forager

Nectar * Forager
Pollen Comb
Pollen Comb

Larvae MRID

Cott on
1 x 0.045 1.26 0.13 0.22 0.03 <0.01

48755606 2 x 0.045 2.54 0.05 0.83 0.04 0.01

2 x 0.089 6.66 0.07 2.78 1.19 0.03

2 x 0.134 2.61 1.01 2.23 0.04 0.0885 Application Rate (lb ai/A) Plant
Pollen * Plant

Nectar Plant

Tissue Forager

Nectar * Forager
Pollen Comb
Pollen Comb

Larvae MRID

Phacelia

1 x 0.021 0.52 b 0.05 0.29 48446601

1 x 0.043 1.48 b 0.09 0.81
Phacelia

1 x 0.006 0.06 a

48445806 1 x 0.012 0.04 a

1 x 0.021 1.76 b 0.61 a

1 x 0.045 0.23 a

1 x 0.088 1.01 a Pumpkin

1 x 0.022 0.08 0.03 0.20 b 48755601

1 x 0.089 0.38 0.03 1.27 b

a Samples taken 7 days after treatment rather than immediately after treatment

b Whole plant samples in 48446601 , flower samples in 48445806 , leaf tissue in 48755601 * Overall maximum reported residue in pollen and nectar used for Tier 1 risk assessment is shown in bold

Honey Bee Pollen and Nectar Consumption Rates

Estimation of honey bee consumption of pollen and nectar depends on the cast e and life stage of
the bee. Consumption rates for different cast e s, life stages and tasks of honey bees have been recently reviewed and summ arized in USEPA (2012). A summary of these consumption rate
estimates is found in Appendix D

. As indicated in Table 42 , the highest consumption rates for worker, drone, a nd queen larvae occur on the last days of their life stage. Therefore, for Tier 1 risk assessment purposes, the latter two days of the worker and dr o ne pollen and nectar consumption rates is used for calculating oral doses of sulfoxaflor. Feedback from t he FIFRA SAP on the draft pollinator risk assessment framework indicated that consumption rates should
be summed across the entire larval life stage. It is noted here that assessment of dos es of sulfoxaflor in royal jelly is not conducted because availabl e data indicate residues in royal jelly are reduced by 100X or greater presumably due to processing of material by nurse bees ( Davis
and Shuel 1988 and Kamel et al . (unpublished) )

. Estimated consumption rates for adult honey bees are provided in Table 43

.

Table 42

. Estimated consumption rates of pollen, nectar and royal jelly by larval honey
bees

Life Stage Caste Average age (in days) * Daily consumption rate (mg/day)

Brood food /

royal jelly Nectar ** Pollen *** Total food

Larval Worker 1 3.75 none none 3.75

2 7.50 none none 7.50

3 15 none none 15

4 none 37 2.7 40

5 none 77 2.7 8086 Life Stage Caste Average age (in days) * Daily consumption rate (mg/day)

Brood food /

royal jelly Nectar ** Pollen *** Total food

Days 4+5 none 114 5.4 119

Drone 5 none 52 unknown 52

6 none 100 unknown 100
Days 5+6 n one 152 Unknown 152

Queen 1 9.4 none none 9.4

2 19 none none 19

3 38.0 none none 38

4 100.0 none none 100

5 203 none none 203

Source : USEPA 2012 Draft Pollinator Risk Assessment Framework; highlighted row indicates consumption rate estimates used for the refined Tier 1 risk assessment; NA = not applicable

* From Winston 1987

** From Rortais et al. 2005. Assumes that average sugar content of nectar is 30%.

*** From Crailsheim et al. (1992, 1993).

Table 43

. Estimated con sumption rates of pollen, nectar and royal jelly by adult honey bees

Life Stage Caste Daily consumption rate (mg/day)

Average Age

(in days) Brood food / royal jelly Nectar ** Pollen *** Total food

Adult Worker (cell cleaning and capping) 0

- 10 none 60 5. 2 65

Worker (brood and queen tending, nurse bees) 6

- 17 none 140 8.85 149

Worker (comb building, cleaning and food handling) 11

- 18 none 60 1.7 62

Worker (foraging for pollen) >18 none 43.5 0.041 44

Worker (foraging for nectar) >18 none 292 0.041 29 2

Worker (maintenance of hive in

winter 0

- 90 none 29 2 31

Drone >10 none 235 0.0002 235

Queen 0+ Unknown unknown None unknown

Source : USEPA 2012 Draft Pollinator Risk Assessment Framework; NA = not applicable

* From Winston 1987

** From Rortais et al

. 2005. Assumes that average sugar content of nectar is 30%.

*** From Crailsheim et al. (1992, 1993).87 Honey Bee Oral Dose Estimation

By combining the maximum reported residues of sulfoxaflor in pollen and nectar with the estimated consumption rates sh own in Table 42 and Table 43

, a total oral dose is estimated.
This oral dose is then divided by the applicable acute oral LD 50 (0.0515 μ g ai/bee for adult
workers and > 0. 2 μ g ai/bee for larvae, respectively ) to derive the acute RQ values ( Table 44 ). Chronic toxicity data of sulfoxaflor to honey bees are not available nor have standardized test protocols for chronic toxicity testing of individual bees been developed. As indicated in Table
44

, RQ s range from <0.8 to 5.7 and exceed the LOC for acute risk (0.4 ) . This indicates that risk to honey bee colonies cannot be precluded and analysis of effects at the whole hive level is warranted (Tier 2). Unlike Tier 1, where risks are expressed quantitatively in the form of RQ values, risk in Tier 2 is described qualitatively and is characterized in Section 5.2, Risk Description.

Table 44

. Refined Tier 1 oral risk quotients for honey bees using maximum reported concentrations in pollen and nectar

Life Stage Cast/Task Average Age (d) Total food Consumption (mg/d) Estimated Oral

Dose (ug ai/bee /d ) 1 Acute RQ 2
, 3

Larvae Worker days 4+5 119 0.151 < 0.8

Drone Days 5+6 152 0.153 < 0.8
Adult Worker (cell cleaning and capping) 0

- 10 65 0.095 1.8 Worker (brood and queen tending, nurse bees) 6

- 17 149 0.200 3.9 Worker (comb building, cleaning and food handling) 11

- 18 62 0.072 1.4 Worker (foraging for pollen) >18 43.5 0.044 0.9 Worker (foraging for nectar) >18 292 0.294 5.7

Worker (maintenance of hive

in winter 0

- 90 31 0.042 0.8

Drone >10 235 0.236 4.6

Queen 0+ unknown unknown unknown

1 Oral dose determined using maximum concentrations of sulfoxaflor in pollen (6.6 mg/kg) and nectar (1.0 mg /kg) reported in Table 41 multiplied by the estimated cast

- specific consumption

rate.

2 Acute RQs determined as the ratio of oral dose to the a cute LD 50 for adult (0.0515 μ g ai/bee) and larval (>0.2 μ g ai/bee) honey bees

3 RQ values in bold exceed the proposed acute risk LOC of 0.4.

Based on the estimate median consumption rates of pollen and nectar shown in Table 42 and
Table 43 , it is clear that the oral exposure of adult and larval honey bees is dominated by the88 consumption of nectar , with more than 90% of the total consumed food source represented by

nectar

. Given the importance of nectar as a source of food and potential contaminant exposure, the concentration in nectar necessary to meet or exceed the proposed acute risk LOC of 0.4 was
determined. Based on the acute LD 50 of 0.05 15 μg a

. i

. /bee and a consumpt ion rate of 292 mg/d
f

or adult nectar foragers, a concentration of > 0.07 ppm in nectar would result in an acute oral RQ that meets or exceeds the proposed LOC of 0.4. The adult nectar forager caste was chosen because it has the highest estimated nectar c onsumption rate among the various castes assessed. A comparison of each of the 8 8 reported residues of sulfoxaflor in cotton nectar reveals that only
4 values (5%) exceeded the 0.07 ppm LOC

- based threshold ( Figure 16 )

. Three of these values are within a factor of two, but one value (1.0 ppm, day 8, 2 x 0.134 lb a.i./A, hive 1) is about 14X above the residue equivalent to the LOC. The vast majority of sulfoxaflor residues in nectar (88%) are less than half the 0.0 7 ppm LOC

- based threshold in nectar. While the concentration of sulfoxaflor in pollen would add to the total dose estimated for nectar foragers, bees, the contribution is very minor and does not affect this interpretation of the results.

Figure 16 . Ratio of sulfoxaflor concentration in cotton nectar to residue associated with the proposed acute LOC of 0.4 0 4 10 13 50

7
3 0 0 1

0 10 20 30 40 50 60

0 0.01 0.05 0.1 0.5 1 2 5 10 15Frequency

Ratio of Nectar Concentration to 0.07 ppm Threshold89 5.2 Risk Description

- Interpretation of Direct Effects

In risk description, the results from the risk estimation are interpreted and synthesized into overall risk conclusions. This description considers other lines of evidence ( e.g ., monitoring data, field data, refined exposure and effects modeling) for ch aracterizing ecological risk. In addition, the risk description also contains a discussion of relevant sources of uncertainty in the risk assessment and sensitivity of the risk assessment findings to important methodological assumptions. The risk descrip ti on also address es other concerns including risks to threatened and endangered species, a discussion of uncertainty, and the sensitivity of risk conclusions to assumptions made in the assessment.

5.2.1 Risks to Aquatic Animals

A summary of the maximum sulfoxaflor acute and chronic RQ values derived for aquatic
animals is shown in Table 45

. N one of these RQ values exceed the applicable acute or chronic
risk LOC . Specifi cally, the acute RQ values are one to two orders of magnitude below the acute risk to listed species LOC of 0.05. The chronic RQ values are one to three orders of magnitude below the LOC, with the exception of saltwater invertebrates, which are within a f actor of two of the LOC of 1.0. As discussed in Section 4, chronic RQ for saltwater invertebrates (benthic and
water column

- dwelling) is based on a NOAEC value for mysid shrimp (0.11 mg a.i./L) that reflects just a 4.5% increase in time to first brood rel ative to controls at the LOAEC of 0.25 mg a.i./L. No other adverse effects were reported at this concentration for mysid shrimp. Thus, there is some uncertainty regarding the biological significance of this endpoint and consequently, in the RQ values, wh ich are just a factor of two below the chronic LOC.

Because sulfoxaflor is a new chemical, no information is available from monitoring data or ecological incident reports. Based on the results of risk estimation, the potential risk to aquatic
animals fr om the proposed uses of sulfoxaflor is presumed low.

Table 45

. Summary of aquatic animal risk profile for sulfoxaflor

Exposure FW Fish
RQ SW Fish
RQ FW Invert. RQ (water

column) SW Invert. RQ (water column) FW Invert. RQ (benthic) S W Invert. RQ (benthic)

Acute <0. 00 01 0.0 002 <0. 00 01 0.009 <0. 0001 0.006
Chronic 0. 08 0.04 0. 0 01 0.5 0.11 0.5 RQ values based on the maximum aquatic EECs derived from the NC Cotton exposure scenario; see Risk

Estimation Section 5.1 for derivation of t hese RQ values

5.2. 2 Risks to Aquatic Plants

Risk quotient values calculated using the maximum peek aquatic EEC and the lowest toxicity endpoint for aquatic vascular and non

- vascular plants are two to three orders of magnitude below
levels of concer n ( Table 33 )

. This finding, combined with knowledge of the mode of action of90 sulfoxaflor ( new class of nicotinic acetylcholine receptor agonist), support a conclusion of low potential risk to aquatic plants.

5.2

. 3 Risks to Terrestrial Organisms

5.2. 3 .1

. Acute and Chronic Risk to Birds and Mammals

A summary of the overall acute and chronic risk profile for sulfoxaflor based on the exposure scenario producing the highest terrestrial EECs and the most sensitive species within each taxonomic group is shown in Table 46

.

Table 46

. Summary of the avian and mammalian risk profile for sulfoxaflor

Exposur e Avian Dose
RQ Avian Dietary
RQ Mammalian
Dose RQ Mammalian Dietary RQ

Acute <0. 7 4 0.01 0.0 2 n/a

Chronic n/a 0. 27 3.8 0. 5 3 RQ values based on the maximum terrestrial EECs derived from 2 x 0.133 lb ai/A, 7 d

interval exposure scenario; see Risk Estimat ion Section 5.1 for derivation of these RQ
values * Refined RQ estimate using a foliar dissipation half life of 12.3 days
Bolded value exceeds chronic risk LOC

For birds (also used as a surrogate for terrestrial

- phase amphibians and reptiles), a potentia l for acute risks is identified using the acute dose

- based RQ approach. Specifically, a maximum RQ of <0.74 was determined using a sulfoxaflor

- specific foliar dissipation half life of 12.3 days. Although a risk potential is indicated by this acute RQ, it is considered uncertain because the acute toxicity study upon which it is based ( i.e

., zebra finch) failed to reach a definitive oral LD 50 because birds regurgitated the dose. Because this regurgitation followed a dose

- dependent response (with 20%

- 100% o f the birds regurgitating at 80 mg a.i./kg bw and higher), regurgitation was judged to be a treatment

- related response. Should such repellency be demonstrated in the wild with contaminated diet, ecologically relevant adverse effects could
occur in absence of suitable (non

- contaminated) forage items. Notably, 0% mortality occurred at
doses of 132 mg a.i./kg

- bw and lower

, but 40% mortality occurred at 200 mg a.i./kg

- bw, the highest dose tested. Since 100% of the birds regurgitated at this dose level, the a ctual exposure may be substantially lower and thus, the LD 50 in absence of regurgitation may be lower than the highest dose tested. The conduct of another acute, dose

- based study (or as an alternative, a dietary study) with passerines in which regurgitati on was avoided would address this source of uncertainty in the avian acute risk estimation. In such a study, the acute oral LD 50 would have to be greater than 560 mg a.i./kg bw in order for acute risks concerns to listed species not to be triggered ( i.e

. , RQ < 0.1).

For mammals, chronic risk concerns were identified based on reproductive effects identified at 24.6 mg/kg/d from a 2

- generation reproductive toxicity study with the rat and modeled EECs for mammalian forage items. Based on the refined chroni c dose

- based RQ values presented in
Table 36 , chronic risk concerns were identified for all of the proposed sulfoxaflor uses for at91 least one diet ary category which comprises four separate pesticide application sce narios. Chronic risk concerns were also identified for at least one dietary item with all size classes modeled (15, 35 and 1000g). However, it should be noted that a significant uncertainty associated with these chronic, dose

- based RQ values pertains to t he duration over which chronic effects to mammals are likely to be manifest. Specifically, these RQ values are derived using the maximum peak concentration of sulfoxaflor that is predicted to occur on dietary items. With a foliar half life of 12.3 days, predicted residues of sulfoxaflor on short grass would decline from a peak of 53.4 ppm (associated with an RQ of 3.8 for 15g mammal) to 14 ppm (associated with an
chronic dose

- based RQ of 1 for 15g mammal) in about 23 days. Over the 365 days in the T

- REX simulation, predicted residues of sulfoxaflor remain above the 14 ppm level (> RQ of 1) for 30 days.

5.2. 3

. 2. Risks to Terrestrial Plants

Risks to terrestrial plants from the proposed uses of sulfoxaflor are not expected based on available toxicity data w hich indicates that at or above the maximum application rate, no deleterious effects on plants was observed. This risk conclusion is also supported by the mode of action of sulfoxaflor, which would not be expected to affect plants at levels that would aff ect target insects.

5.2. 3

. 3. Risks to Bees

a) Tier 1 Risk Assessment

As indicated in Section 5.1.3.5 (Risk Estimation for Bees) , the Tier 1 risk estimation indicates a potential risk to bees at the i ndividual (organism) level through the acute, oral route of exposure using the maximum residues reported from available residue studies. Specifically, risks above
the proposed acute risk LOC value were identified for all cast e s of bees modeled with the or al route of exposure ( Table 44 ). Acute oral RQ values range from 0.8 to 5.7 across all cast e s of
adult worker and larval bees examined.

A number of u ncertainties associated with the Tier 1 risk estimation for s ulfoxaflor are noted and further described in this section, with attention to how they may affect the tier 1 risk conclusion.
These include :

• use of maximum residue reported in pollen and nectar to represent exposure to all bee casts and all crops

• lack of chronic toxicity data for adult and larval bees (and longer

- term exposure to pupae)

• selection of the toxicity endpoint from the larval toxicity test ( e.g ., NOAEC vs. LD 50 )

• accuracy of consumption rate estimates used for various bee cast e s

• variation in pes ticide residues in pollen and nectar

• conservation of pesticide dose from plant tissue to the hive

Use of Maximum Reported Residues. As described in Section 5.1.3.5 , the Tier 1 risk assessment for bees is based on the maximum reported residue of sulfoxaflo r in pollen and nectar (6.6 and 1.0 ppm, respectively) . These values were obtained from the cotton residue study using92 application rates ranging from 0.045 to 0.134 lb a.i./A

. Plots of this residue data are shown in Figure 17 for sulfoxaflor residues in plant pollen ( P anel A ), forager

- collected pollen ( P anel B ),
and forager

- collected nectar (P anel C) over the 10

- d residue collection period. For plant pollen, applications were made on Day 0 (all treatments) and D ay 5 (three treatments).
Residue data shown in P anel A of Figure 17 indicate a rapid decline in sulfoxaflor concentrations in cotton pollen immediately following pesticide applications. This steep decline may be r elated to cotton flowers remain ing open for pollination for approximately 1 day followed by withering, closure and drying on subsequent days (Ritchie et al ., 2004; Smith, 2012). Therefore, samples taken from flowers between application days would represen t flowers that were closed prior to pesticide applications. It is also worthy to note that an expected

treatment

- dependent trend in residue concentrations in plant pollen was not consistently seen in this study. This suggests that these data are subject to sources of variation that mask the expected trend of higher residues in plant pollen with higher pesticide application rate. Although
selection of the maximum residue in plant pollen for Tier 1 risk assessment may reflect a level of
conservatism in the assessment, the high variability in residue concentrations suggest that even the maximum observed concentration in pollen may not reflect the overall maximum residue in cotton plant pollen. Furthermore, results from sulfoxaflor residues measured in forag er

- collected pollen ( P anel B ) demonstrate that bees were repeatedly collecting pollen with 1

- 2 ppm. Use of these values instead of the 6.6 ppm maximum for pollen consumption would not alter the Tier 1
risk conclusions.

Regarding the selection of the ma ximum residue reported in nectar (1.0 ppm from hive 1 at2 x
0.134 lb a

. i

. /A; Appendix D ), results from Figure 17 (Panel C) indicate that this value is about
an order of ma gnitude greater than the next highest concentration measured in nectar. Results
shown in P anel C of Figure 17 reflect mean values across two hives. Unexpectedly, this
maximum concentration in nectar occurred in b etween application days (day 8), which likely reflects systemic translocation of sulfoxaflor from the prior applications on days 0 and 5. If the next greatest concentration of sulfoxaflor in nectar were used instead of the overall maximum (e.g., 0.1 vs. 1 .0 ppm), risks to larvae would be below LOCs but those for adult foragers would
still exceed the LOC of 0.4.

Lack of Chronic Toxicity Data . Another uncertainty in the Tier 1 risk assessment is lack of chronic toxicity endpoints for adult and larval bees . Although the submitted toxicity tests for honey bee larvae were intended to provide such information, limitations in the study design precluded use of results from beyond day 7 of these studies. Therefore, to the extent that adults
and larvae are more sensitive to sulfoxaflor over greater exposure durations, results from this
Tier 1 risk assessment will underestimate chronic risk to bees.93 Figure 17 . Sulfoxaflor residues in cotton plant pollen (A), forager

- collected pollen (B) and forager collected nectar (C). Forager

- collected pollen and nectar residues are a mean from
bees at two hives in each tunnel ( MRID 48755606 ). 0.00 0.20 0.40 0.60 0.80 1.00 1.20 1.40 1.60 1.80

0 1 2 3 4 5 6 7 8 9 10 11`Mean Sulfoxaflor in Forager Pollen (ppm)

Days After 1st Application 1 x 0.045 lb ai/A

2 x 0.045 lb ai/A

2 x 0.089 lb ai/A

2 x 0.134 lb ai/A 

### B 0.001 0.01 0.1

1 10

0 1 2 3 4 5 6 7 8 9 10 11Sulfoxaflor in Plant Pollen (ppm)

Days After 1st Application 1 x 0.045 lb ai/A

2 x 0.045 lb ai/A

2 x 0.089 lb ai/A

2 x 0.134 lb ai/A 

### A

0.0001 0.001 0.01 0.1

1

0 1 2 3 4 5 6 7 8 9 10 11Mean Sulfoxaflor in Forager Nectar (ppm)

Days After 1st Application 1 x 0.045 lb ai/A

2 x 0.045 lb ai/A

2 x 0.089 lb ai/A

2 x 0.134 lb ai/A 

### C94 Selection of Larval Toxicity Endpoint. As noted in Section 4, the larval toxicity endpoint
selected for this analysis is >0.2 ug ai/bee. This value is a “non

- definitive” LD 50 because mortality at the highest test concentration (45%) did not exceed 50%. Although use of this non

definitive LD 50 value introduces some uncertainty in the Tier 1 risk assessment, the close proximity of the mortality response (45%) to 50% suggests that the actual LD 50 value would likely be relatively close to the 0.2 ug ai/bee value used in the assessment. The 7

- d LD 50 value
would have to be more than a factor of 2 lower than 0.2 in order to change the risk conclusions
for larval bees.

Consumption Rates of Pollen and Nectar. The consumption rate estimates of pollen and nectar used for Tier 1 risk assessment are subject to considerable variability and uncertainty, as
described in USEPA (2012). However, values represent median estimates (rather than high

- end) in order to avoid compounding multiple conservative assumptions on the risk assessment results. Since nectar consumption rates drive the Tier 1 risk estimates for adult nect ar foragers, the consumption rate would have to be more than 14 times lower than the 292 mg/day used in this risk assessment (less than 20 mg/day) in order for RQ values to be below the proposed LOC of
0.4.

Variability in Residue Concentrations. One sou rce of uncertainty in the Tier 1 risk assessment for honey bees relates to the variability in reported sulfoxaflor concentrations in pollen and nectar following foliar applications. Besides the overall high variability is observed in residue
concentration s over time, reported concentrations in pollen and nectar do not consistently exhibit an expected proportional increase with pesticide application rate ( Figure 17 ). With plant collected pollen, the maximum concent ration on Day 0 occurred in the second highest treatment (2 x 0.089 lb a.i./A) while that for Day 5 occurred for the third highest treatment (2 x 0.045 lb a.i./A). In terms of average concentrations of pesticide, similar inconsistencies in proportionally of residues with pesticide application rate are apparent ( Figure 18 ). For example, mean residues in plant pollen associated with the highest application rate (2 x 0.134 lb a.i./A) are about one third of correspondi ng mean residues from the next lower application rate (2 x 0.089 lb a.i./A). The reason for this lack of expected proportionality of pesticide concentrations in pollen is not
understood and introduce s uncertainty in that reliability of scaling pesticide r esidues according to application rate.

Conservation of Pesticide Dose. Another uncertainty associated with the Tier 1 risk assessment (particularly for larval bees) is the assumption that storage and processing of pollen and nectar by bees does not reduc e pesticide exposure to brood. In the cotton study, residues in pollen collected from the comb were generally lower than that from plants or foragers. However, the maximum overall residue reported was 1.2 ppm from day 5 of the second highest treatment (2 x 0.089 lb ai//A) which is similar to the overall maximum reported in plant pollen (6.6 ppm). This suggests that at least in terms of overall maximum concentrations, the assumption that residues in pollen collected outside the comb are similar to pollen stored inside the comb does not appear to be unreasonably conservative.95 Figure 18 . Mean sulfoxaflor residues in plant

- collected cotton pollen over different application intervals ( MRID 48755606 )

b) Tier 2 Risk Assessment

A t otal of six Tier 2 semi

- field (tunnel) studies were submitted by the registrant examining the effects of sulfoxaflor on the honey bee at the colony

- level. These studies are relevant to this
assessment because results of the Tier 1 risk assessment indicate a potential risk to individual adult and larval honey bees ( Section 5.1.3.5 ). As noted previously, there are uncertainties
associated with the results of Tier 1 assessment because effects are assessed at the
level of the individual bee under controlled laboratory conditions. By quantifying effects at the whole colony level, Tier 2 studies incorporate the combined impact of a chemical stressor ( e.g ., sulfoxaflor) on honey bee castes and their numerous inter

- dependent and potentially compensatory functio ns within the hive. Furthermore, semi

- field exposure of bees to the pesticide is controlled to a significant extent in that bees are forced to forage on treated crop due to confinement in the mesh tunnel. Although semi

- field tunnel studies are advantageou s in these and other aspects relative to laboratory toxicity studies on individual bees, they also have significant limitations. One limitation includes the relatively short time span that bees can be exposed within the tunnels due to stress associated wi th confinement (generally no more than 7

- 14 days). The adequacy of the forage base (nectar, pollen) is considered suboptimal compared to the diverse array of pollen and nectar sources available in natural settings where bees can forage freely. Despite the se limitations, semi

- field tunnel studies are considered an important line of evidence for evaluating the effects of pesticides on bees at the whole colony level.

The salient features and primary risk conclusions associated with each of the six semi

- field
studies are summarized in ( Table 47 ). A discussion of measured effects of sulfoxaflor on various individual and colony

- level endpoints is provided below. Additional details of each study are provided in Appendix D

. 0.26 0.28 1.35

0.55

0.003 0.53

0.14 0.05

0.00 0.20 0.40 0.60 0.80 1.00 1.20 1.40 1.60

1 x 0.045 lb ai/A 2 x 0.045 lb ai/A 2 x 0.089 lb ai/A 2 x 0.134 lb ai/AMean Sulfoxaflor Concentration(ppm)

Application Frequency and Rate Mean (day 0

- 4) Mean (day 5

- 10)96 Study Design Summary. All six tunnel studies differed substantially in their overall design. For example, Hecht

- Rost (2009) used a regression

- type design which included five different application rates rangi ng from 0.006 to 0.088 lb ai/A with one replicate (tunnel) per treatment. Similarly, Ythier (2012) evaluated four different application rates ranging from 0.045 to 0.134 lb ai/A) with one replicate tunnel per treatment. The studies by Schmitzer (2010; 20 11a,b,c) used a hypothesis

- based test design with fewer treatments but three replicate tunnels per treatment with application rates ranging from 0.004 to 0.043 lb a.i./A. Although this design permitted statistical analysis via hypothesis testing, the high variability in response endpoints combined with the small number of replicates (3) resulted in low statistical power for detecting potential treatment

related effects in the vast majority of comparisons. Therefore, observed differences in mean

responses across treatments are also emphasized in addition to statistical differences to determine whether any trends were apparent across treatments/controls.

Regarding the timing of pesticide applications, Schmitzer (2010) evaluated sulfoxaflor applications duri ng and after bee flight, while Schmitzer (2011a,b) evaluated applications prior to bloom in addition to during and after bee flight. Schmitzer (2011c), Ythier (2012), and Hecht

Rost (2009) evaluated applications only during bee flight.

The duration of the observation period post

- application also differed widely across studies.
Hecht

- Rost (2009) and Schmitzer (2010) included no observations after hives were removed from the exposure tunnels. Schmitzer (2011a,b,c) included a 10

- d, 17

- d and 90

- d post tun nel (post

- exposure) observation period, respectively. Ythier (2012) evaluated effects after 7 days post exposure.

It is also important to note that the time of year when each study was initiated also differed among the studies. Tests were started in Jun e (for Schmitzer 2011a), July (for Schmitzer 2011b), August (for Hecht

- Rost 2009, Schmitzer 2010, and Ythier 2012) and October (for Schmitzer 2011c). Since honey bee colonies typically show strong seasonal increases and declines over the course of spring, summer and fall, the timing of the study can be an important factor to consider when interpreting the results.

Lastly

, in terms of the relevance of the foliar applications to the proposed registration of
sulfoxaflor in the U S , it is noted that a ll but t he Ythier (2012) study used application rates that were substantially below the maximum proposed application rate in the US ( i.e., below single rate of 0.133 lb ai/A and the yearly maximum rate of 0.266 lb ai/A).

Forager Mortality. Five of the semi

- field studies summarized in Table 47 and Appendix D included measures of forager bee mortality determined from observations of dead bees collected away the hive and from dead be e traps at the hive entrances during the period of confinement in the tunnels. In general, the mortality pattern of adult forager bees was similar across the five tunnel studies. A spike in mortality up to 20 times that of control hives was observed on t he day of pesticide application (0 day after application; 0DAA). Subsequent to 0DAA, forager bee mortality declined sharply and recovered to levels similar to control hives within 3 days, sometimes less. For studies that included identical application rat es during and after bee flight (Schmitzer 2010; 2011a,b), the magnitude of forager bee mortality was generally greater when97 pesticide was applied during bee flight compared to after bee flight, likely reflecting the combined effect of exposure via direct c ontact and via contact and/or ingestion residues on plants. The lack of sustained mortality of adult foragers following pesticide applications at rates
from 3

- 67% of the maximum single rate proposed in the US suggests that the direct effects of
sulfoxaflo r on foraging bees ( i.e ., those effects resulting from exposure from direct contact with spray droplets and residues on plants) are relatively short

- lived. However, the potential for
indirect effects of short

- term loss of foragers on brood development and colony strength over the longer

- term (e.g., through pre

- mature recruitment of hive bees into the forager work force) at maximum US application rates has not been quantified. Although Ythier (2012) used the maximum single and seasonal application rates, t hey did not quantify the effects of sulfoxaflor on forager bee mortality since this study was intended to measure sulfoxaflor residues in plant tissues, not biological effects.

In the context of toxicity from dried residues on plants, the lack of sustaine d mortality to forager bees from residues applied after bee flight is consistent with the results from the foliar residue toxicity study ( MRID

- 47832512 ) which showed < 15% mortality after exposure to aged foliar
residues from 4 hr to 24 hours.

Forager Fl ight Activity. The effect of sulfoxaflor on forager bee flight activity generally reduced the activity immediately following pesticide application. Hecht

- Rost (2009), Schmitzer (2010) and Schmitzer (2011a, b) all reported reductions in flight activity up to 5 times lower than controls on 0DAA. By 3DAA, however, flight activity was similar to control levels in these
studies. No obvious treatment

- related effects on flight activity were reported by Schmitzer (2011c); however, the application rates used wer e very low relative to the proposed maximum US rate (3

- 16% of the maximum proposed rate). Overall, these results suggest that at rates from
3

- 67% of the maximum single rate proposed in the US, the direct effects of sulfoxaflor on flight activity of foragi ng bees ( i.e ., those effects resulting from exposure from direct contact with spray droplets and residues on plants) are relatively short

- lived. The effects of sulfoxaflor on the flight activity of foraging bees at maximum application rates proposed in th e US have not been quantified.

Behavior Abnormalities. Similar to adult forager mortality and flight activity, the occurrence
of behavior abnormalities ( e.g. uncoordinated movement, spasms or an intensive cleaning behavior) was short

- lived at the studied application rates (3

- 67% of US maximum). The frequency of these behavioral abnormalities was relatively low and they were not sustained beyond 2 days after pesticide application.

Brood Development. The suitability of the submitted semi

- field studies fo r quantifying the effects of sulfoxaflor on developing honey bee brood is very limited, even when they are considered apart from limitations associated with the use of low application rates. Hecht

- Rost (2009) and Schmitzer (2010) evaluated brood after onl y 7 and 9 days exposure, which is far short
of the recommended duration of semi

- field studies by OECD Guideline 75. A longer post

exposure evaluation time is necessary in order to evaluate the effects over an entire honey bee brood cycle (21 days for work ers). Furthermore, these two studies also held bees in tunnels for much longer than recommended prior to exposure (8

- 11 days vs. 2

- 3 days recommended by98 OECD Guideline 75), which may have confounded interpretation of brood development results as colony be es may have experienc ed undue stress from prolonged confinement of hives in the tunnel. Schmitzer (2011c) included a long post

- exposure observation period (3 months); however, the study was initiated in late October and brood development and colony

- streng th were already in a state of significant decline due to the late season in which the study was conducted. This uncertainty is supported by the lack of discernible effects on brood at 14DAA by either reference toxicant (dimethoate or fenoxycarb) used in t he study. Ythier (2012) evaluated brood pattern at 10DAA and 17DAA (close to an entire brood cycle), but did not include a control treatment in order to make appropriate comparisons. It is noted, however, that this study was not designed to provide a com prehensive evaluation of biological effects; rather it was designed to quantify sulfoxaflor residues in various plant matrices. Although pre

- and post

application assessments of brood can be compared ( Table 47 ), i t is not possible to distinguish the effects of tunnel confinement from those of sulfoxaflor on brood development based on pre

- and post

- exposure comparisons alone. Adverse effects resulting from tunnel confinement in the cotton study by Ythier (2012) is considered possible (if not likely) because cotton pollen is
known to be a sub

- optimal source of pollen to honey bees ( Vaissiere et al. , 1994 ) and bees were not able to maintain sufficient pollen stores over the course of the tunnel exposure.

Apart from their low applications rates (16

- 32% of the proposed US maximum), the two studies with the most suitable design for evaluating the effects of sulfoxaflor on honey bee brood are Schmitzer (2011a,b). Both studies included adequate post

- application observat ion periods (20

- 53 days), used three replicates/treatment, and tracked the development of a defined cohort of marked brood over time (rather than overall brood pattern on the comb). By following the development of individual brood, two indices of brood d evelopment were derived ( i.e ., brood termination index and brood compensation index) according to OECD Guideline 75. The brood termination index is simply the proportion of brood that fails to develop fully through emergence. The brood compensation inde x is a reflection of the average of the five development stages achieved by the brood cohort (with 1 = egg, 2 = young larvae, 3 = old larvae, 4 = pupae, 5= empty cell [emerged] or cell re

- filled with egg/larva).

In both studies, Schmitzer (2011a,b) rep orted a high average brood termination rate in control hives of 56% and 65%, respectively. This means that over half the brood in control hives failed to emerge and transition to adult bees. Although no specific acceptability criteria have been
defined b y OECD for this index in controls, these values exceed brood termination rates of controls reported by an inter

- laboratory study supporting the development of OECD Guideline 75 (Schur et al ., 2003). Notably, Schur et al. reported that brood termination rat e in control hives varied from 8% to 43% in a ring

- test of five trials of the OECD 75 tunnel study design. The
authors attributed the high brood termination rates (32

- 43%) in three trials to poor weather conditions that occurred during the studies. In a recent review of historical control data for
brood term ination rate, Pistorius et al ., (2011) correlated increases in control brood termination
rate with lateness in the season of test initiation and smaller available forage area in the tunnels. Regardles s of the source of the high brood termination ra te in the control treatments from Schmitzer (2011a,b), it likely reflects stress on the bees caused by the study design and creates substantial uncertainty as to the ability to detect the potential effects of sulfoxaflor on developing
brood. A large increase in brood termination rate (98

- 100%) was observed for the reference99 toxicant (fenoxycarb) for these two studies , which indicates that despite the high larval mortality in control hives, a major catastrophi c impact on brood could be detected

. Importantly, t he application rates of fenoxycarb (300 g ai/ha or about 2X the maximum single application rate identified in the US) are specifically intended to cause catastrophic impacts on developing brood
in order t o demonstrate that the study design was sufficie nt to detect effects on brood. Although the effects of sulfoxaflor applications on brood development are uncertain due to high mortality of larvae in controls, these results suggest that the overall effects were less than the catastrophic losses experienced by the colonies exposed to the reference toxicant.

The results from the brood compensation index indicated no obvious or statistical differences in treatments compared to controls by 22DAA and 21DAA for S chmitzer (2011a,b), respectively. The average brood compensation rate in control and sulfoxaflor

- treated hives ranged from 3.0 to 4.2. This indicates that on average, honey bee broods were able to reach an older larval or pupal stage. Therefore, these r esults suggest that the high brood termination rate discussed previously occurred principally at the latter stages of brood development. Since the brood compensation and termination indices are related, the uncertainty associated with high brood terminati on rate in controls also impacts the interpretation of the brood compensation index responses. In both studies, a large reduction in brood compensation index (1.7

- 1.9) indicates the effects of the reference toxicant (fenoxycarb) were discernible in this st udy.

Taken as a whole and in consideration of their respective limitations, the results from the six tunnel studies are unable to conclusively demonstrate whether sulfoxaflor applications adversely impact brood development, even at the lower application r ates used.

Colony Strength. Measures of colony strength (number of bees occupying the combs) were available from 5 of the 6 tunnel studies submitted ( Table 47 ). Assessment relative to concurrent
control hives wa s possible in 3 studies (one study had no concurrent control and the other had compromised controls). In general, effects of sulfoxaflor on colony strength were slight or not apparent with the three studies with controls (Schmitzer 2011a,b,c). A 15

- 28% r eduction in mean colony strength was apparent through most of the exposure period for the treatment with
the two highest application rates ( 0.043 lb ai/A pre

- bloom and after flight). However, a similar study conducted by the same authors (Schmitzer 2011b) found no obvious difference in colony strength with 0.043 lb ai/A applied pre

- bloom. Similarly, Schmitzer (2011c) found no obvious difference in colony strength of treatments compared to controls by 14DAA. However, it should be noted that application ra tes used in this study were very low (3

- 16% of US maximum) and it
was conducted late in the season as colonies were in a natural state of decline in terms of brood production.

When colony strength is evaluated by comparing pre

- and post

- application measu rements within a sulfoxaflor treatment, no treatment

- related difference is apparent in the study by Hecht

- Rost (2009) measured at 7DAA or Ythier (2012) measured at 10 days after first application (10DAFA and 17DAFA. The similarity in colony strength measu rements taken pre

- and post application within and among all treatments reported for the cotton study (Ythier 2012) implies that
conditions of the sulfoxaflor treatments did not result in an obvious decline in mean colony strength by 17DAFA, even at the ma ximum US application rate of 2 x 0.134 lb ai/A. Although100 lack of a current control and limited observation period precludes definitive conclusions regarding the effect of sulfoxaflor on colony strength in this study, these results suggest that major impac ts on honey bee colony strength are not apparent with sulfoxaflor applications at the maximum US application rate, at least over the short term ( e.g., 17DAFA).

Overall Conclusions from Tier 2 Assessment. Results from the Tier 2 semi

- field studies suggest that at the application rates used (3

- 67% of US maximum), the direct effects of sulfoxaflor on adult forager bee mortality, flight activity and the occurrence of behavioral abnormalities is relatively short

- lived, lasting 3 days or less. Direct effects a re considered those that result directly from interception of spray droplets or dermal contact with and ingestion of foliar residues. The direct effect of sulfoxaflor on these measures at the maximum application rate in the US is presently not known. The effect of sulfoxaflor on brood development is
considered inconclusive due to the aforementioned limitations associated with these studies. When compared to controls, the effect of sulfoxaflor on colony strength applied at 3

- 32% of the US maximum proposed rate was either not apparent or modest at most (based on one study). Sulfoxaflor applied to cotton foliage up to the maximum rate proposed in the US did not result in an observable decline in mean colony strength by 17DAFA when compared to colonies assess ed 3 days prior to application. Additional data would be needed to determine the potential effects of sulfoxaflor applications on brood development and long

- term colony health at the maximum application rates proposed in the US. Such data would include on e or more Tier 2 semi

- field
tunnel stud ies conducted according to OECD 75 guidance. It is further noted that the high variability in sulfoxaflor residues from the cotton residue study and the nature of the cotton flowering introduces uncertainty in the ex trapolation of these residue results to other crops

. Therefore, additional data on the nature and magnitude of sulfoxaflor residues in one or more pollinator

- attractive crops would be needed to address this source of uncertainty.101 Table 47

. Summary of Tier 2 colony

- level studies conducted with sulfoxaflor

Study Attribute Results Summary

1. Hecht

- Rost (2009)

MRID

- 48445806 2. Schmitzer (2010)

MRID 48445807 3. Schmitzer (2011a)

MRID 48755604 4. Schmitzer (2011b)

MRID 48755605 5. Schm itzer (2011c) (no MRID) 6. Ythier 2012

MRID 48755606 Application Timing & Rate During flight : 0.006

- 0.088 lb ai/A (6

- 99 g ai/ha) During flight : 0.021

- 0.043 lb ai/A (24 & 48 g ai/ha)

After flight : 0.043 lb ai/A (48 g ai/ha) Pre bloom : 0.043 lb ai/A (48 g ai/ha)

After flight : 0.021

- 0.043 lb ai/A (24 & 48 g ai/ha)

During flight : 0.021 lb ai/A (24 g ai/ha) Pre bloom : 0.043 lb ai/A (48 g ai/ha)

After flight : 0.021 lb ai/A (24 g ai/ha)

During flight : 0.021 lb ai/A (24 g ai/ha) During flight : 0.00 4, 0.007, 0.021 lb ai/A (4, 8, 24 g ai/ha) During flight : 0.045 lb ai/A x 1 (50 g ai/ha x 1) 0.045 lb ai/A x 2 (50 g ai/ha x 2) 0.089 lb ai/A x 2 (100 g ai/ha x 2) 0.134 lb ai/A x 2 (150 g ai/ha x 2) No. Reps. /

Treatment 1 3 3 3 3 1

% of US Max. Sing le Appl.

Rate 4

- 67% 16

- 32% 16

- 32% 16

- 32% 3

- 16% 34

- 100%

Crop Phacelia Phacelia Phacelia Phacelia Phacelia Cotton Exposure Pathways
Assessed Direct contact, dermal, oral Direct contact, dermal,
oral During flight: Direct contact, dermal, oral

Pre

- bloom, a fter flight: dermal, oral During flight: Direct contact, dermal, oral

Pre

- bloom, after flight: dermal, oral Direct contact, dermal,
oral Direct contact, dermal,
oral102 Study Attribute Results Summary

1. Hecht

- Rost (2009)

MRID

- 48445806 2. Schmitzer (2010)

MRID 48445807 3. Schmitzer (2011a)

MRID 48755604 4. Schmitzer (2011b)

MRID 48755605 5. Schm itzer (2011c) (no MRID) 6. Ythier 2012

MRID 48755606 Exposure Duration, Month of Study

Initiation In

- Tunnel Exposure : (pre

- application) 11 d

(post

- application) 7d

Post Tunnel Obs.:
0d

August In

- Tunnel Exposure : (pre

- application) 8d

(post

- application) 9d

Post Tunnel Obs. : 0d

August In

- Tunnel Exposure : (pre

- application, after & during flight) 3d (pre

- application, pre

bloom) 0 d

(post

- application, after & during flight) 7d (post

- application, pre

bloom) 10d

Post Tunnel Obs. : 20d

June In

- Tunnel Exposure : (pre

- application, after & during flight) 10d (pre

- application, pre

bloom) 0d

(post

- application, after & during flig ht) 7d (post

- application, pre

bloom) 17d

Post Tunnel Obs. : 53d

July In

- Tunnel Exposure : (pre

- application) 8d

(post

- application) 7d

Post Tunnel Obs. : 90d (colony survival)

October In

- Tunnel Exposure : (pre

- application) 3 d

(post

- application) 10d

Post Tunnel Obs.:
7d

August

- September

Forager Mortality Day 0 : up to 7X increase (treatment dependent) Day 3

- 7 : ≈ control levels; Day 0 : Up to 20X

increase Day 3

- 7 : ≈ control
levels Day 0

- 1 : up to 8X increase in mortality Days 2

- 7 : treat ≈
controls Days 8

- 27 (post tunnel): treat ≈ controls Day 0 : up to 3X ↑ Days1

- 7 : no consistent
difference vs.
controls** Da y 0 : up to 4X ↑; Day 1

- 7 : treatments ≈
controls Not assessed

Flight Intensity Day 0 : up to 5X decrease (dose

dependent) Day 3

- 7 : Dose

independent
decrease Day 0 : up to 2X
decrease Days 1

- 7 : treatment ≈
controls Some reduction seen (during and after bee flight), but recovery to control levels by D2

- 4 Day 0 : some (<50%)
reduction vs. controls Day 1

- 7 : treatment ≈
controls No obvious treatment
related effects on foraging activity, but late season may have
confounded results Not assessed

Forager
Behav ior Light intoxication symptoms (D0AA only ) Some behavioral
abnormalities < 2DAA Some behavior
abnormalities observed

on 0DAA in 1
treatment, none thereafter No behavioral
abnormalities observed
at any treatment Some behavior
abnormalities observed

on 0DAA in 24 g ai/ha,

none thereafter Not assessed103 Study Attribute Results Summary

1. Hecht

- Rost (2009)

MRID

- 48445806 2. Schmitzer (2010)

MRID 48445807 3. Schmitzer (2011a)

MRID 48755604 4. Schmitzer (2011b)

MRID 48755605 5. Schm itzer (2011c) (no MRID) 6. Ythier 2012

MRID 48755606
Brood Development Treat vs. Control:
Inconclusive Pre vs. Post Appl.:

- Dose

- dependent ↓in % Larvae

- Dose

- independ. ↓ in % capped brood Treat vs. Control:

- no statistical or obvious difference @
9DAA;

Pre vs. Post:

- no statistical or obvious differences;

- modest ↓% capped and ↑ % empty cells may reflect emergence Treat vs. Control: Brood compensation
index:

- no statistical or
obvious treatment related effects @

22DAA

- Brood termination

rate :

- inconclusive Treat vs. Control: Brood compensation
index:

- no statistical or
obvious treatment related effects @

21DAA

- Brood termination

rate:

- inconclusive Treat vs. Control: Brood pattern: treat ≈ controls through
14DAA, but late season may have confounded
results No control was
included Pre vs. Post Appl. Brood pattern:

- %larvae, %pupae, reduced ~ 2X @
10DAA;

- % pollen ~
0% @ 10DAA

- %nectar > pre

- appl.
levels

- % adult bees within

20 % of pre

- appl levels Colony Strength Treat vs. Control:
Inconclusive Pre vs. Post Appl.:

10

- 25% dose

independent ↓ Not assessed Treat vs. Control: Up to 15

- 28 % reduction in 48g ai/ha through 27DAA (pre bloom) and 15DAA (after flight) Treat vs. Co ntrol:

- treatments ≈ controls up through 60DAA Treat vs. Control:

- treatments > controls, but late season may
have confounded
results

- By D90AA, on ly 1/18 colonies failed (8 g/ ha) Pre vs. Post Appl. Hive strength similar

across treatments
before an d after application

Study
Limitations* 1. Varroa infestation
in controls 2. Long pre

- exposure period in tunnels (11d) 3. High variability among colonies prior
to exposure
4. Short observation period (7d) 5. 1 rep/treatment
6. Low % larvae in

contro ls (7DAA) 1. L ong pre

- exposure period in tunnels (8d)
2. Short observation period (9d) 3. High overall variability within treatments (n=3) 4. No colony strength

measurements 1. Poor control performance re: brood termination rate (56%) 2. High overall

varia bility within treatments (n=3) 1. Poor control performance re: brood termination rate (65%)

2. L ong pre

- exposure period in tunnels (10d) 3. high overall variability within treatments (n=3) 1. All colonies in steep
decline in brood
condition due to late season (Oct). rendering the ability to detect
treatment effects

uncertain 1. No concurrent
control was included for interpreting biological effects*** 2. one replicate /

treatment
3. short observation period (17d)104 Study Attribute Results Summary

1. Hecht

- Rost (2009)

MRID

- 48445806 2. Schmitzer (2010)

MRID 48445807 3. Schmitzer (2011a)

MRID 48755604 4. Schmitzer (2011b)

MRID 48755605 5. Schm itzer (2011c) (no MRID) 6. Ythier 2012

MRID 48755606
Reference
Toxicant Effects Dimethoate ( 400g/ha);

- similar brood pattern as controls (except % larvae)

- colony strength similar to treatments;

- sustained ↑in # dead bees;

- sustained ↓flight intensity Dimethoate (600g/ha);

- similar brood pattern
as controls

- sustained ↑in # dead bees;

- sustained ↓flight intensity Fenoxycarb (300g /ha)

- Brood compensation: sustained ↓ vs.

controls over 22DAA

- Brood termination: major impact (98%)

- c olony strength: generally sustained
reduction vs. controls Fenoxycarb (300g /ha

& Dimethoate 600g/ha:

- c olony strength: generally sustained ↓

- brood compensation: sustained ↓

- Brood termination:

major impact (98

- 100%) Dimethoate (600g/ha), Thiamethoxam (50g /ha) :

- Brood pattern: similar to controls through

14DAA Not assessed

* Except for Ythier (201 2), these limitations are in addition to the use of application rates below the proposed U.S. maximum single rate of 0.133 lb ai/A ** 1 of 3 tunnel replicates at 48 g ai/ha showed increased mortality over days 1

- 7AA, but it is uncertain if this is treatmen t related. *** this study was designed to assess residues of sulfoxaflor in plant and hive matrices, not biological effects.105 Overall Bee Risk Assessment Conclusions:

In considering multiple lines of evidence, including results of Tier 1 risk assessm ent, the mode of action of sulfoxaflor, the nature of its uptake and persistence in plant tissues, and results (and limitations) of the Tier 2 studies, the potential impact of the proposed uses of sulfoxaflor at maximum application rates on developing bee brood and colony strength cannot be precluded.

5.2. 4 Review of Incident Data

Incident reports submitted to EPA since approximately 1994 have been tracked by assignment of EIIS (Environmental Incident Information System) in an Incident Data System (IDS). Over the
2012 growing season, a Section 18 emergency use was granted for application of sulfoxaflor to cotton in four states (MS, LA, AR, TN). To date, no incident reports have been received in
association with the use of sulfoxaflor. However, due to the nature of ecological incident reporting, absence of incidents cannot be construed with absence of incidents.

5.2. 5 Endocrine Effects

Under the Federal Food, Drug and Cosmet ic Act (FFDCA), as amended by the Food Quality Protection Act (FQPA), EPA is required to develop a screening program to determine whether certain substances (including all pesticide active and other ingredients) “may have an effect in
humans that is simila r to an effect produced by a naturally

- occurring estrogen, or other such endocrine effects as the Administrator may designate.” Following the recommendations of its Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC), EPA determined
that there was scientific basis for including, as part of the program, the androgen

- and thyroid hormone systems, in addition to the estrogen hormone system. EPA also adopted EDSTAC’s recommendation that the Program include evaluations of potential effects in wildlife. For pesticide chemicals, EPA will use FIFRA, to the extent that effects in wildlife may help determine whether a substance may have an effect in humans, and the FFDCA authority to require the wildlife evaluations. As the science develops and t he resources allow, screening of additional hormone systems may be added to the Endocrine Disruptor Screening Program (EDSP). When the appropriate screening and or testing protocols being considered under the Agency’s Endocrine Disruptor Screening Program have been developed, s ulfoxaflor may be subjected to additional screening and or testing to better characterize effects related to endocrine disruption.

5.2. 6 Threatened and Endangered Species Concerns

For listed species assessment purposes, the action area is considered to be the area affected directly or indirectly by the Federal action and not merely the immediate area involved in the action. At the initial screening

- level, the risk assess ment considers broadly described taxonomic groups and so conservatively assumes that list species within those broad groups are collocated106 within the pesticide treatment area. This means that terrestrial plants and wildlife are assumed to
be located on or adjacent to the treated site and aquatic organisms are assumed to be located in a surface water body adjacent to the treated site. The assessment also assumes that the listed species are located within an assumed area which has the relatively highest poten tial exposure to the pesticide, and that exposures are likely to decrease with distance from the treated area.

If the assumptions associated with the screening

- level action area result in RQs that are below the listed species LOCs, “no effect,” determin ation conclusion may be made with respect to listed species in that taxa (for direct effects), and no further refinement of the action is necessary. Furthermore, RQs below the listed species LOCs for a given taxonomic group indicate no
concern for indirec t effects upon listed species that depend upon the taxonomic group as a resource. However, in situations where the screening assumptions lead to RQs in excess of the risk to listed species LOCs for a given taxonomic group, a potential “may affect,” conclu sion exists and may be associated with direct effects on listed species belonging to that taxonomic group or may extend to indirect effects upon listed species that depend on that taxonomic group as a resource. In such cases, additional information on the biology of the listed species, the locations of these species, and the locations of use sites could be considered along with available information on the fate and transport properties of the pesticide to determine the extent to which screening assumptions regarding an action area apply to a particular listed organism. These subsequent refinement steps could consider how this information would impact the action area for a particular listed organism and may potentially include areas of exposure that are dow nwind and downstream of the pesticide use site.

In conducting a screen for indirect effects, direct effects LOCs for each taxonomic group are used to make inferences concerning the potential for indirect effects upon listed species that rely

upon non

- lis ted organisms in these taxonomic groups as resources critical to their cycle. Pesticide use scenarios resulting in RQs that are below all direct effect listed species LOCs for all taxonomic groups assessed are considered of no concern for risks to listed species either by
direct or indirect effects.

For sulfoxaflor, the potential direct effects to listed species should they co

- occur with application sites are indicated for mammals (chronic toxicity) and birds (including terrestrial

- phased amphibians and r eptiles; acute toxicity), non

- target terrestrial insects ( using honey bee as a surrogate); freshwater benthic insects (chronic toxicity) and saltwater invertebrates (acute toxicity. Risk to listed species LOCs are not exceeded for plants. For the maximum proposed sulfoxaflor applica tion rates, there may be a potential concern for direct effects to the following groups of organisms:

• Birds

• Mammals

• Terrestrial

- phase reptiles

• Terrestrial

- phase amphibians

• Terrestrial insects

• Aquatic invertebrates107 A spatial co

- occurrence analysis would be necessary to delineate the action area. However, given the potential widespread use of sulfoxaflor based on the proposed labels, the action area would likely encompass wide portions of the United States.

5.2. 7 Description of Assumptio ns, Limitations, Uncertainties and Data Gaps

5.2. 7 .1 Exposure for All Taxa

There are a number of areas of uncertainty in the aquatic and terrestrial risk assessments. The toxicity assessment for terrestrial and aquatic plants and animals is lim ited by the number of species tested in the available toxicity studies. Use of toxicity data on representative species does not provide information on the potential variability in susceptibility among species to acute and chronic exposures.

For each pro posed use, the risk assessment is based on the maximum application rate on the proposed label. The frequency at which actual uses approach these maximum scenarios is dependent on the resistance to the pesticide, the timing of applications, and market force s. Exposure and risks could be overestimated if the actual application rates, frequency of application, or number of applications are lower than the input parameters used for the conservative exposure scenario that was modeled

5.2. 7 .2 Exposure for Aquatic Species

This Tier II risk assessment relies on best available estimates of environmental fate and physicochemical properties, maximu m application rate of sulfoxaflor

, application frequency and
interval. However, several uncertainties and model limitations are noted and should be considered in interpreting the results of this aquatic risk assessment.

• The frequency at which actual sulfoxaflor uses approach the use estimates modeled is dependent on resistance to the insecticide, timing of applications, and market forces. In general, model output values represent the upper

- bound estimates of concentrations that might be observed in s urface water due to the application of sulfoxaflor , given available
data and model limitations.

• Major uncertainties associated with the standard runoff scenario include the physical construct of the watershed and representation of vulnerable aquatic en vironments for different geographic regions. The physicochemical properties (pH, redox conditions,

etc .) of the standard farm pond are based on a Georgia farm pond. These properties are likely to be regionally specific because of local hydrogeological co nditions. Any alteration in water quality parameters may impact the environmental behavior of a pesticide. The farm pond represents a well mixed, static water body. Because the farm pond is a static water body (no flow through), it does not account for pesticide removal through flow through or water releases. The lack of flow through the farm pond provides an environmental condition for accumulation of persistent pesticides. The assumption of108 uniform mixing does not account for stratification due to th ermoclines ( e.g. , seasonal stratification in deep water bodies). Additionally, the dimensions of the standard runoff scenario assume a watershed area to water body volume ratio of 10 ha: 20,000m 3 . This
ratio is recommended to maintain a sustainable const ructed pond in the Southeastern United States. The use of higher watershed area to water body volume ratios (as recommended for sustainable ponds in drier regions of the United States) may lead to higher pesticide concentrations when compared to the stand ard watershed area to water body volume ratio.

• The standard runoff scenario assumes uniform soils and agronomic management practices across the standard 10

- hectare field. Soils can vary substantially across even small areas; this variation is not refle cted in the model simulations. Additionally, the impact of unique soil characteristics and soil management practices ( e.g. , tile drainage) are not considered in the standard runoff scenario. The assumption of uniform site and management conditions is not expected to represent some site

- specific conditions. Extrapolating the risk conclusions from the standard pond scenario to other aquatic habitats ( e.g. , marshes, streams, creeks, and shallow rivers, intermittent aquatic areas) may either underestimate or overestimate the potential risks in those habitats.

• For an acute risk assessment, there is only a one

- day averaging time for exposure. Use of such a “peak” concentration, with a 1

- in

- 10 year annual return frequency, implies that exposure is suf ficient to elicit acute effects comparable to those observed over more protracted exposure periods tested in the laboratory, typically 48 to 96 hours. In the absence of data regarding time

- to

- toxic event analyses and latent responses to peak exposure, the degree to which risk is overestimated cannot be quantified.

5.2. 7 .3 Exposure for Terrestrial Species

This risk assessment reli es on the best available estimates of environmental fate and physicochemical properties, maximum application rate of sulfoxaflor , maximum number of applications, and the shortest interval between applications. However, several uncertainties and
model limi tations are noted and should be considered in interpreting the results of this terrestrial
risk assessment.

a) Location of Wildlife Species

For screening terrestrial risk assessments, a generic bird or mammal is assumed to consume 100% of its diet as treated seeds from the application site. This assumption may lead to an overestimation of exposure to species that do not occupy the treated field. The actual habitat requirements of any particular terrestrial sp ecies are not considered, and it is assumed that species occupy, exclusively and permanently, the treated area being modeled. This assumption leads to a maximum level of exposure in the risk assessment.109 b) Routes of Exposure

Dietary Exposure

Screening

- level risk assessments for spray applications of pesticides assume that 100% of the diet is relegated to single food types foraged only from treated fields. These assumptions are likely to be conservative for many species and will tend to overestimate potential risks when species are foraging on multiple sources of food ( i.e ., not just treated seeds). Furthermore, while the assumption of 100% diet from a treated area may be reasonable worst case assumption for acute exposu res, this assumption is likely much less applicable to long

- term (chronic) exposures modeled as single food types composed entirely of treated seeds. Data on the amount of wildlife diet composed of seeds from treated fields would be needed to reduced this uncertainty.

Dermal Exposure

The screening assessment does not consider dermal exposure of terrestrial organisms to sulfoxaflor

. The Agency is actively pursuing modeling techniques to account for dermal exposure via direct application of spray and by in cidental contact with contaminated vegetation,
soil and water.

Drinking Water Exposure

Drinking water exposure to a pesticide active ingredient may be the result of consumption of surface water or consumption of the pesticide in dew or other water on th e surfaces of treated vegetation. For pesticide active ingredients with a potential to dissolve in runoff, puddles on the treated field may contain the chemical. The SIP tool (version 1.0) was used to assess the potential for exposure concerns to birds an d mammals via drinking water alone. Sulfoxaflor ’s solubility in water ( 1,380 mg/L) and toxicity to avian and mammalian species are inputs for the potential upper

- bound drinking water calculations . Because the test of most sensitive avian species (zebra fi nch) did not produce a definitive LD 50 value, the lowest concentration tested that resulted in no significant effects was used as an upper

- bound estimate of acute toxicity ( >80 mg a.i./kg bw ) was used as the toxicity endpoint for birds for SIP. For mammal s, an LD 50 of 1000 mg/kg bw was used ( rat )

. Chronic NOAE C /NOAE L toxicity values used for birds and mammals
are 2 00 ppm (mallard) and 6.07 mg/kg bw ( rat ). Based on this information, sulfoxaflor exposure through drinking water alone has the potential to be a relevant acute or chronic exposure route exposure route of concern for mammals or birds.110 c) Incidental Pesticide Releases Associated with Use

This risk assessment is based on the assump tion that the entire treatment area is subject to
sulfoxaflor application at the rates specified on the label. This translates to an even seeding rate across an entire field. In reality, there is the potential for uneven application of sulfoxaflor throug h such plausible incidents as changes in calibration of application equipment, spillage, and localized releases at specific areas of the treated field that are associated with specifics of the type of application equipment

d) Residues in Pollen and Nectar

Residue information is available for three plant species: pumpkin, cotton and Ph acelia

. As noted previously, there are limitations in these data which contribute to uncertainty in the Tier 1 risk
assessment fo r bees. Specifically, the pumpkin residue data reflect systemic transport only and were collected several days after pesticide application. The Ph acelia residue data are from application rate lower than the proposed U.S. maximum and are very limited for pollen and nectar. The cotton study contains the most extensive residue information available, However, the high variability in sulfoxaflor residues from the cotton residue study and the nature of the cotton flowering ( i.e., open for only one day) introdu ces uncertainty in the extrapolation of these residue results to other crops. Therefore, additional data on the nature and magnitude of sulfoxaflor residues in one or more pollinator

- attractive crops would be needed to address this source of uncertainty.

5.2. 7 .4 Effects Assessment for All Taxa

a) Age Class and Sensitivity of Effects Thresholds

It is generally recognized that test organism age may have a significant impact on the observed sensitivity to a toxicant. The screening risk assessment acute toxicity data for fish are collected on juvenile fish and aquatic invertebrate acut e testing is performed on recommended immature age classes. Similarly, acute dietary testing with birds is also performed on juveniles, with mallard being 5

- 10 days old and quail at 10

- 14 days of age.

Testing of juveniles may overestimate the toxicity o f direct acting pesticides in adults. As juvenile organisms do not have fully developed metabolic systems, they may not possess the ability to transform and detoxify xenobiotics equivalent to the older/adult organism. The screening risk assessment has no c urrent provisions for a generally applied method that accounts for this uncertainty. In so far as the available toxicity data may provide ranges of sensitivity information with respect to age class, the risk assessment uses the most sensitive life

- stage i nformation as the conservative screening endpoint.111 b) Lack of Effects Data for Amphibians and Reptiles

Currently, toxicity studies on amphibians and reptiles are not required for pesticide re gistration. Since these data are lacking, the Agency uses fish as surrogates for aquatic

- phase amphibians and birds as surrogates for terrestrial

- phase amphibians and reptiles. If other species are more or
less sensitive to sulfoxaflor than the surrogates , risks may be under

- or overestimated, respectively. The Agency is not limited to a base set of surrogate toxicity information in establishing risk assessment conclusions. The Agency also considers toxicity data on non

standard test species when available . Further research is needed to determine whether, in general, reptiles and terrestrial

- phase amphibians are suitably represented by bird species in assessing risks for sulfoxaflor and fish are an appropriate surrogate for aquatic

- phase amphibians.

c) Use of the Most Sensitive Species Tested

Although the screening

- level risk assessment relies on a selected toxicity endpoint from the most sensitive species tested, it does not necessarily mea n that the selected toxicity endpoints reflect sensitivity of the most sensitive species existing in a given environment. The relative position of the most sensitive species tested in the distribution of all possible species is a function of the
overall v ariability among species to a particular chemical. The relationship between the sensitivity of the most sensitive tested species versus wild species (including listed species) is unknown and a source of significant uncertainty. In addition, in the case of listed species, there is uncertainty regarding the relationship of the listed species' sensitivity and the most sensitive species tested.

d) Brood Development and Colony

- Level Effects

As described in Section 5.2.3.3

, the results from the available semi

- field tunnel studies are
insuffic ient for concluding whether sulfoxaflor applications adversely impact brood development, even at the lower application r ates used. Additional data would be needed to determine the potential effects of sulfoxaflor applications on brood development and long

- term colony health at the maximum application rates proposed in the US. Such data would include on e

or more Tier 2 semi

- field tunnel stud ies conducted according to OECD 75 guidance.



### 6. **L ITERATURE**  

### C **ITED**

6.1 Environment al Fate Studies Submitted to EPA

MRID 47832149 Laughlin, L. A., 2009, Hydrolysis of XDE

- 208 at pH 5, 7, and 9 , Dow AgroSciences LLC. Report Number: 070102, Report Date: 3

- Mar

- 2009; 38 pages.112 MRID 47832283 M. Ma, 2010, Aqueous Photolysis of XDE

- 208 and X11719474 in pH 7 Buffer Under Xenon Light, Dow AgroSciences LLC. Report Number: 090073, Report Date: 6

- May

- 2010; 86 pages.

MRID 47832284 R. N, Yoder, 2010, Natural Water Photolysis of XDE

- 208 a nd the X11719474 Metabolite under Xenon Light, Dow AgroSciences LLC. Report Number: 090088, Report Date: 1

- Apr

- 2010;69

pages.

MRID 47832014 Laughlin, L. A., Adelfinskaya, Y., Balcer, J. L., 2010, Aerobic Transformation of XDE

- 208 in Two European Aquatic S ediment Systems , Dow AgroSciences LLC. Report Number: 080138, Report Date: 18

- Mar

- 2010. 97 pages.

MRID 47832277 R. N. Yoder, A. G. Stephon., 2010, Anaerobic Aquatic Degradation of XDE

- 208 in Two US Sediment and Pond Water Systems , Dow AgroSciences LLC. Re port Number: 070105, Report
Date: 8

- Jun

- 2010. 83 pages.

MRID 47832018 R. N. Yoder., D. Liu, 2010, Adsorption/Desorption of XDE

- 208 and Adsorption of Three XDE

208 Soil Metabolites, Dow AgroSciences LLC. Report Number: 080161, Report Date: 4

- Jan

2010. 153 pages.

MRID 47865578 D. Liu, R. N. Yoder, Y. A. Adelfinskaya, 2010, Aerobic Degradation of XDE

- 208 in Four US Soils, Dow AgroSciences LLC. Report Number: 080130, Report Date: 11

- Jun

- 2010. 107 pages.

MRID 47832013 R. N. Yoder, A. G. Stephon, J. L. Balce r, 2009. Aerobic and Anaerobic Degradation of XDE

- 208 in Four European Soils, Dow AgroSciences LLC. Report Number: 080129, Report Date: 8

- Sep

2009. 177 pages.

MRID 47832279 M Simmonds, 2010, XDE

- 208: Degradation in One Soil under Anaerobic Conditions Fol lowing Incubation under Aerobic Conditions. Battelle UK Ltd, for Dow AgroSciences LLC. Report Number: YR/09/011 (DAS Number: 101398), Report Date: 13

- Jul

- 2010. 98 pages.

MRID 47832013 R. N. Yoder, A. G. Stephon, J. L. Balcer, 2009. Aerobic and Anaerobic D egradation of XDE

- 208 in Four European Soils, Dow AgroSciences LLC. Report Number: 080129, Report Date: 8

- Sep

2009. 177 pages.113 MRID 47832280 B. M. Wendelburg, 2010, Aerobic Soil Degradation Rate of X11579457 in 4 European Soils, Dow AgroSciences LLC. Rep ort Number: 080146, Report Date: 29

- Jun

- 2010. 109 pages.

MRID 47832281 B. M. Wendelburg, 2010, Aerobic Soil Degradation Rate of X11519540 in 4 European Soils, Dow AgroSciences LLC. Report Number: 080147, Report Date: 28

- Jun

- 2010. 105 pages.

MRID 478322 82 A. C. Newcombe,T. Negley, I. J. van Wesenbeeck, 2010, Dissipation of XDE

- 208 in Soil under Cropped
and Bare

- Soil Conditions at Multiple Sites Across North America, Dow AgroSciences LLC. Report
Number: 080008, Report Date: 23

- Jul

- 2010. 2

, 383 pages

.

MRID 47832269 Wendelburg BM (2010)Method validation study for the determination of residues of XDE

- 208 and its major metabolites in soil using offline solid

- phase extraction and liquid chromatography with tandem mass spectrometry detection. Dow AgroSciences In dianapolis Lab; Company Report Number 091185; GLP, Unpublished study submitted by Dow AgroSciences.

MRID 47832256 Gravelle W (2010) Independent laboratory validation of the analytical methodology used for the
determination of SCE

- 208 (X11422208) and its m etabolites (X11519540, X11579457, and X11719474) in sandy loam and clay loam soils. Eurofins Product Safety Labs; Company Report Number 101100, GLP, unpublished study submitted by Dow AgroSciences.

MRID 47832270 Robaugh DA (2010) Method validation for the determination of residues of XDE

- 208 and its major metabolites in soil by on

- line solid phase extraction and high performance liquid chromatography with tandem mass spectrometry. Pyxant Labs Inc; Company Report Number 081078; GLP, unpublished study submit ted by Dow AgroSciences.

MRID 47832268 Wendelburg BM (2010) Method validation study for the determination of residues of XDE

- 208 and its major metabolites in water using offline solid

- phase extraction and liquid chromatography with tandem mass spectrometr y detection; Dow AgroSciences Indianapolis Lab; Company Report Number 091186; GLP, unpublished study submitted by Dow AgroSciences.

MRID 47832267 Independent laboratory validation of Dow AgroSciences LLC method Determination of residues
of XDE

- 208 and it s major metabolites in water using offline solid

- phase extraction and liquid chromatography with tandem mass spectrometry detection; JRF America Study Number KP

2010

- 08; Company Report Number 101650; GLP, unpublished study submitted by Dow AgroSciences.114 M RID 47832266 Robaugh DA (2010) Method validation for the determination of residues of XDE

- 208 and its major metabolites in water by on

- line solid phase extraction and high performance liquid chromatography with tandem mass spectrometry; Pyxant Labs Inc. St udy Number 081078

- 1906B; Company Report Number 101078, GLP, unpublished study submitted by Dow AgroSciences.

MRID 47832265 Merdian H (2010) the development and validation of a method for the analysis of XDE

- 208 in air. PTRL Europe GmbH; Company Report Num ber 09113, GLP, unpublished study submitted by Dow AgroSciences.

Crop Residue

- Decline Studies

MRID 48755703 Olivier de Cirugeda Helle2012. Sulfoxaflor Crop Residue Decline Summary Report. Dow AgroSciences LLC Study ID: RSB

- 007.

6.2 Ecological Effe cts Studies Submitted to EPA

6.2.1 Aquatic Ecotoxicity Studies

MRID 47832105 Bergfield A (2008). X11719474: Acute toxicity to the rainbow trout, Oncorhynchus mykiss

, determined under static tes t conditions. ABC Laboratories Inc. Company Report Number 080054

MRID 47832106 Bergfield A (2008). X11719474: Acute toxicity to the water flea, Daphnia magna , determined
under static

- renewal test conditions. ABC Laboratories Inc. Company Report Number 080 055

MRID 47832109 Gerke A (2008). XDE

- 208: Whole sediment 10 day acute toxicity test with midge larvae ( Chironomus dilutus ). ABC Laboratories Inc. Company Report Number 080076

MRID 47832110 Gerke A (2008). XDE

- 208: Acute toxicity test to the sheepshead minnow, Cyprinodon variegatus , determined under static test conditions. ABC Laboratories Inc. Company Report
Number 080067

MRID 47832111 Gerke A (2008). XDE

- 208: Acute toxicity test to the rainbow trout, Oncorhynchus mykiss,
determined under static test conditions. ABC Laboratories Inc. Company Report Number 080064, USEPA, PMRA Document Number 1941488115 MRID 4783212 Gerke A (2008). XDE

- 208: Acute toxicity test to the bluegill sunfish, Lepomis macrochirus

, determined under static test conditions. ABC Labora tories Inc. Company Report Number 080065

MRID 47832113 Gerke A (2008). XDE

- 208: Acute toxicity test to the common carp, Cyprinus carpio , determined under static test conditions. ABC Laboratories Inc. Company Report Number 080066

MRID 47832114 Hicks SL ( 2008). XDE

- 208: Static acute toxicity test with the water flea, Daphnia magna ABC Laboratories Inc. Company Report Number 080068

MRID 47832115 Hicks SL (2008). XDE

- 208: Effect on new shell growth of the eastern oyster ( Crassostrea virginica ). ABC Laborat ories Inc. Company Report Number 080070

MRID 47832117 Hicks SL (2009). XDE

- 208: Static acute toxicity test with the mysid shrimp, Americamysis
bahia . ABC Laboratories Inc. Company Report Number 080069

MRID 47832121 Dengler D (2009). Testing of effects of XDE

- 208 on the single cell green alga, Pseudokirchneriella subcapitata in a static 96 h test. Eurofins GAB GmbH. Company Report
Number 080439

MRID 47832122 Denger D (2009). Testing of effects of XDE

- 208 on the marine diatom Skeletonema costatum in

a st atic 96 h test Eurofins GAB GmbH. Company Report Number 080440

MRID 47832123 Denger D (2009). Testing of effects of XDE

- 208 on the diatom Navicula pelliculosa in a 96 h static test. Eurofins GAB GmbH. Company Report Number 080441

MRID 47832124 Dengler D (2009). Testing of effects of XDE

- 208 on the blue

- green alga Anabaena flos

- aquae in a 96 h static test. Eurofins GAB GmbH. Company Report Number 080442

MRID 47832125 Kuhl R, Wydra V (2009). Toxicity of XDE

- 208 technical to the aquatic plant Lemna gibba in a
semi

- static growth inhibition test. Institut fur Biologische Analytik. Company Report Number
080443

MRID 47832126116 Bottcher M, Wydra V (2009). Toxicity of XDE

- 208 technical to fathead minnow ( Pimephales promelas ) in an early

- life stage test. Institut fur Biologische Analytik. Company Report Number
080444

MRID 47832127 Kuhl R, Wydra V (2009). Influence of XDE

- 208 technical to Daphnia magna in a reproduction test. Institut fur Biologische Analytik. Company Report Number 080445

MRID 47832128 Lehman C (2 010). XDE

- 208: Life

- cycle toxicity test of the saltwater mysid, Americamysis
bahia , conducted under flow

- through conditions. ABC Laboratories Inc. Company Report
Number 090534

MRID 47832129 Hicks SL (2010). XDE

- 208: Early life

- stage toxicity test with th e sheepshead minnow, Cyprinodon variegatus , under flow

- through conditions. ABC Laboratories Inc. Company Report
Number 101286

Gerke A (2009). XDE

- 208 chronic toxicity in whole sediment to freshwater midge, Chironomus riparius. ABC Laboratories Inc Compan y Report Number 080072

6.2.2 Avian Ecotoxicity Studies

MRID 47832072 Hubbard PM, Beavers JB (2009). XDE

- 208 Technical: An acute oral toxicity study with the
zebra finch Wildlife International Ltd. Company Report Number 080061

MRID 47832073 Hubbard PM, Beavers JB (2009). X11719474: An acute oral toxicity study with the northern
bobwhite. Wildlife International Ltd. Company Report Number 080053

MRID 47832074 Hubbard PM, Martin KH, Beavers JB (2008). XDE

- 208: A dietary LC 50 study with the northern
bobwhi te. Wildlife International Ltd. Company Report Number 070260

MRID 47832101 Hubbard PM, Beavers JB (2008). XDE

- 208: An acute oral toxicity study with the northern
bobwhite Wildlife International Ltd. Company Report Number 070261

. MRID 47832104117 Hubbard P M, Martin KH, Beavers JB (2008). XDE

- 208: A dietary LC 50 study with the mallard. Wildlife International Ltd. Company Report Number 070259

MRID 47832119 Temple DL, Martin KH, Beavers JB, Jaber M (2009). XDE

- 208 TGAI: A Reproduction Study
with the Northern Bobwhite. Wildlife International Ltd. Company Report Number 080437

MRID 47832120 Temple DL, Martin KH, Beavers JB, Jaber M (2009). XDE

- 208 TGAI: A reproduction study
with the mallard. Wildlife International Ltd. Company Report Number 080438

Mammalian Toxicity Studies

MRID 47832040 Brooks KJ, Wiescinski CM, Andrus AK, Golden RM (2008)

. XDE

- 208: Acute oral toxicity study in Crl:CD1(ICR) mice (up and down procedure)

. Stockbridge Technology Centre Company Report Number 081059

MRID 47832144 Brooks KJ, Wi escinski CM, Andrus AK, Golden RM (2008)

. XDE

- 208: Acute oral toxicity study in F344/DuCrl rats (up and down procedure)

. Toxicology & Environmental Research and Consulting, Dow Chemical Company

, Company Report Number 081058

.

MRID 47832142 Rasoupour RJ, A blotny CL, Crissman JW, Rick DL, Thomas J (2010)

. XDE

- 208: Two generation dietary reproductive toxicity study in CRL:CD(SD) rats Toxicology & Environmental Research and Consulting, Dow Chemical Company Company Report Number 091023

.

MRID 47832505 Durando, J. (2009) Acute Oral Toxicity Up and Down Procedure in Rats. Eurofins|Product Safety Laboratories, Dayton, New Jersey, US. EPSL Study Number: 27566. Issue date 18 August 2009. Unpublished. (Dow Study Number: 090348).

MRID 47832407 Durando, J. (2009) Acu te Oral Toxicity Study in Rats: Acute Toxic Class Method. Eurofins|Product Safety Laboratories, Dayton, New Jersey, US. EPSL Study Number: 26524. Issue date 25 February 2009. Unpublished. (DOW Study Number: 080049). PMRA #1941141..

6.2.3 Beneficial In sect Ecotoxicity Studies

MRID 48446601118 Liepold, K. (201 1 )

. GF

- 2626: A Semi

- field Study to Investigate Residues in Honeybee Products (Apis mellifera carnica L.; Hymenoptera, Apidae) in Phacelia tanacetifolia in Germany in 2010

. Dow Study ID 110414

MRID 48 445806
Hecht

- Rost, S. (2009)

. GF

- 2032: A Semi

- Field Study to Evaluate Effects on the Honeybee Apis mellifera carnica L.; (Hymenoptera, Apidae) in Phacelia tanacetifolia in France in 2008. Dow Study ID 080349

MRID 48445807 Schmitzer, S. (2010)

. Toxicity Testing of GF

- 2032 on Honey Bees ( Apis mellifera L.) under
Semi

- Field Conditions

- Tunnel Test. Dow Study ID 080083

Schmitzer, S. (201 1c )

. Toxicity Testing of GF

- 2626 on Honey Bees ( Apis mellifera L.) under Semi

Field Conditions

- Tunnel Test . Dow Stu dy ID 101602

MRID 48445809 Vinall S (2010)

. Laboratory bioassay to determine the acute oral toxicity of X11721061 to the honeybee, Apis mellifera Dow Company Report Number 120536

- A

MRID 47832102 Bergfield A (2007). XR

- 208: Acute contact toxicity test wit h the honeybee, Apis mellifera . ABC Laboratories Inc. Company Report Number 070171

MRID 47832103
XR

- 208: acute oral toxicity test with the honeybee, Apis mellifera. ABC Laboratories Inc. Company Report Number 070172

MRID 47832107 Vinall S (2009). Labor atory bioassay to determine the acute oral toxicity of X11719474 to the honeybee, Apis mellifera . Mambo

- Tox Ltd. Company Report Number 080056

MRID 47832417 Vinall S (2009). Laboratory bioassay to determine the acute oral toxicity of GF

- 2032 to the honeyb ee, Apis mellifera
Mambo

- Tox Ltd. Company Report Number 080080

MRID 47832418 Vinall S (2009). GF

- 2032: Laboratory bioassays to determine the acute oral and contact toxicity
of GF

- 2032 to the bumblebee, Bombus terrestris . Mambo

- Tox Ltd. Company Report Num ber
080084

MRID 47832419 Vinall S (2009). Laboratory bioassay to determine the acute contact toxicity of GF

- 2032 to the honeybee, Apis mellifera . Mambo

- Tox Ltd. Company Report Number 08008111 9 MRID 47832420 Lee B (2008). GF

- 2032: Toxicity of residues on foliage to the honeybee, Apis mellifera. ABC Laboratories Inc. Company Report Number 080082

MRID 47832511 Vinall S (2010). Laboratory bioassay to determine the acute contact toxicity of GF

- 2372 to the honeybee, Apis mellifera . Mambo

- Tox Ltd. Company Rep ort Number 090152

MRID 47832512 Bergfield A (2009). GF

- 2372: Toxicity of residues on foliage to the honeybee, Apis mellifera

. ABC Laboratories Inc Company Report Number 090151

MRID 48755601 Dively, G.P. (201 2 )

. Determination of sulfoxaflor residues in various plant tissues following foliar application of low and high rates of the insecticide. Dow Study ID RSB

- 006

MRID 48755602 Stempniewicz A (2012)

. XDE

- 208: Acute toxicity effects to honeybee larvae ( Apis mellifera L.) under laboratory conditions ( in vitro ). Dow Company Report Number 120536

- A

MRID 48755603 Stempniewicz A (2012)

. XDE

- 208: Chronic toxicity effects to honeybee larvae ( Apis mellifera L.) under laboratory conditions ( in vitro ). Dow Company Report Number 120536

- B

MRID 48755604
Schmitzer , S. (2011 a )

. Study on the Effect of GF

- 2626 on Honey Bees and their Brood ( Apis mellifera L.) under Semi

- Field Conditions

- Tunnel Test . Dow Study ID 101599

MRID 48755605 Schmitzer, S. (2011 b )

. Study on the Effect of GF

- 2626 on Honey Bees and their Brood ( Apis mellifera L.) under Semi

- Field Conditions

- Tunnel Test. Dow Study ID 80755

MRID 48755606 Ythier, E. (2012)

. Sulfoxaflor: a semi

- field study in cotton treated with GF

- 2372 (sulfoxaflor 50% WP) to determine residues in matrices relevant to exposure of honeybees and honey bee brood, to enable estimation of exposure of a typical honey bee colony. Dow Study ID 110603

6.3 Open Literature and Government Reports

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Brosch. 1993. Pollen utilization in non

- breeding honeybees in winter. J. Insect Physiol

. 39 (5): 369

- 373.

Crailsheim, K.,Schneider, L.H.W; Hrassnigg, N.; Bühlmann, G.; Brosch, U.; Gmeinbauer, R.;
and B. Schöffmann. 1992. Pollen consum ption and utilization in worker honeybees ( Apis mellifera carnica ): dependence on individual age and function. J. Insect Physiol ., 38 (6):
409

- 419.

Davis, A.R. and R.W. Shuel. 1988. Distribution of C(14)

- Labeled carbofuran and dimethoate in royal jelly, q ueen larvae and nurse honeybees. Api dologie , 19 (1): 37

- 50.

Fletcher, J.S., J.E. Nellesson and T. G. Pfleeger. 1994. Literature review and evaluation of the
EPA food

- chain (Kenaga) nomogram, an instrument for estimating pesticide residues on plants. Env iron. Tox. Chem . 13(9):1383

- 1391.

Hoerger, F. and E.E. Kenaga. 1972. Pesticide residues on plants: correlation of representative data as a basis for estimation of their magnitude in the environment. IN: F. Coulston and F. Corte, eds., Environmental Qual ity and Safety: Chemistry, Toxicology and Technology. Vol 1. George Theime Publishers, Stuttgart, Germany. pp. 9

- 28.

Kamel, A.; Dively, G.; Hawthorn, D. and J. Pettis. Unpublished research examining the fate of imidacloprid and its metabolites in honey bee hives.

Pistorius, J. et al. 2011. Effectiveness of method improvements to reduce variability of brood

t ermination rate in honeybee brood studies under semi

- field conditions. International
Commission For Plant

- Bee Relationships Bee Protection Group 11 th International Symposium Hazards Of Pesticides To Bees. Wageningen, The Netherlands, November 2

- 4, 2011.

Ritchie, G, Bednarz, C, Jost, P, Brown, S. 2004. Cotton growth and development. Bulletin 1252. University of Georgia , Cooperative Extension Service

.

Rortais, A., Arnold, G., Halm, M.P., F. Touffet

- Briens. 2005. Modes of honey bees exposure to systemic insecticides:estimated amounts of contaminated pollen and nectar consumed by different categories of bees. Apidologie, 36: 71

- 83

Schur, A., et al. 2 003. Honey bee brood ring

- test in 2002: method for the assessment of side effects of plant protection products on the honey bee brood under semi

- field conditions.
Bull. Insectol. 56(1):91

- 96.

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