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. 20460
ii

Table of Contents

1. Executive Summary.............................................................................................................. 8

1.1. Nature of Chemical Stressor................................................................................................ 8

1.2 Potential Risks 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 Regulatory 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 ........................................................................................ 66
iii

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 Terrestrial 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 Risk 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 Effects Assessment for All Taxa..................................................................... 110

6. Literature Cited ................................................................................................................. 111

6.1 Environmental Fate Studies Submitted to EPA............................................................. 111

6.2 Ecological Effects 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..................................................................... 119
iv

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

Figure 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 the 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 downstream 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 cotton 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 48755606).......................................................................................................... 95
v

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 measurement 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 abiotic systems 32

Table 7. Fate properties of sulfoxaflor parent and major degradate X-474 in biotic systems..... 33

Table 8. Parent degradation products for systems described in Table 7, above ........................... 34

Table 9. Selected environmental degradates of sulfoxaflor.......................................................... 36

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”).................................................................................................. 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

Table 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 permitted 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 Sulfoxaflor 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 EECs54

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 saltwater 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 ....................................................................................................................... 74
vi

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 

plants............................................................................................................................................. 76

Table 34. Maximum acute dose-based risk quotients for mammals............................................. 77

Table 35. Maximum chronic diet-based risk quotients for mammals .......................................... 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 plant 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 

concentrations in pollen and nectar............................................................................................... 87

Table 45. Summary of aquatic animal risk profile for sulfoxaflor ............................................... 89

Table 46. Summary of the avian and mammalian risk profile for sulfoxaflor ............................. 90

Table 47. Summary of Tier 2 colony-level studies conducted with sulfoxaflor......................... 101
vii

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 Results
8

1. EXECUTIVE SUMMARY

1.1. Nature of Chemical Stressor 

Sulfoxaflor (N-[methyloxido[1-[6-(trifluoromethyl)-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 of the nicotinic acetylcholine receptor 

(nAChR) and exhibits excitatory responses including tremors, followed by paralysis and 

mortality in target insects. In laboratory experiments, sulfoxaflor has been highly efficacious 

against target insects that display resistance to neonicotinoids such as imidacloprid, which is 

classified by the Insect Resistance Action Committee (IRAC) as subclass 4A. Sulfoxaflor 

consists of two diastereomers in a ratio of approximately 50:50 with each diastereomer 

consisting 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/stone), 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 contact 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 environment include: X11719474 (X-474; “major

to dominant”), X11579540 (X-540; “minor to major”), and X11579457 (X-457; “minor”). 

Following consideration of exposure and toxicity for the residues of interest (that is parent, X474 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 

consistent 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 is 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 provides a summary of the environmental risk conclusions for aquatic and terrestrial 

organisms, based on risk quotient (RQ) values and whether they exceed 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

Invertebrates (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 listed 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 identified. Specifically, acute, dose-based RQ 

values calculated using a refined dissipation half-life (DT50) 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 because 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 dosebased RQ values up to 3.8 were determined using a refined DT50 and exceed the 

risk to listed species LOC of 0.1 for at least one mammalian dietary category and 

size class across 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 expected 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 acute 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 single 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 their design and conduct.

* includes: Citrus, Fruits-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 surrogate for terrestrial phase amphibians and reptiles.
10

1.3 Conclusions - Exposure Characterization 

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 m3 mole-1

, respectively at 25 °C). The 

chemical is characterized by a water solubility ranging from 550 to 1,380 ppm. Partitioning 

coefficient of sulfoxaflor from octanol to water (Kow= 6) suggests low potential for 

bioaccumulation in aquatic organisms such as fish. 

Sulfoxaflor reaching the soil system is subjected to rapid aerobic bio-degradation (t1⁄2 <1 day) 

while that reaching foliage may enter the plant tissue and persist much longer. Sulfoxaflor has

shown to be stable to hydrolysis/ photolysis on soil and in aquatic environments. In field studies, 

sulfoxaflor has 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 chemical can be characterized by very high to high mobility (Kfoc ranged from 11-72 mL g1

). 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 applications 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 systems. Adsorption data 

for these degradates indicate that they can be characterized by very high to high mobility for X474 (Kfoc ranged from 7-68 mL g-1

) and very high mobility for X-457 and X-540 (Kfoc ranged 

from 2-44 mL g-1 for X-457 and Kfoc ranged from 1-25 mL g-1 for X-540). Both surface and 

ground water contamination is expected from these three degradates following leaching drift/runoff 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, sulfoxaflor 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 sulfoxaflor 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 

profile 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 toxicity (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 LD50 values of 

0.05 and 0.13 μg a.i./bee, respectively, for adult honey bees (Apis mellifera). For larvae, a 7-d 

oral LD50 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 neonicotinoids where similar cleavage of 

the cyanide group appears to eliminate their insecticidal activity. The acute 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 bees 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 assessment on honey bees. Five of the six 

semi-field studies used application rates ranging from 3 to 67% of the single maximum rate of 

0.133 lb a.i./A proposed for the US. The one semi-field study that used maximum US 

application rates was intended for quantifying 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 abnormalities. 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 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-application 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, 

sulfoxaflor applied to cotton foliage up to the maximum rate proposed in the US resulted 
12

in no discernible decline in mean colony strength by 17days after the first application. 

Longer-term results were not available from this study nor were concurrent controls

included. 

1.5 Data Gaps and Uncertainties 

1.5.1 Environmental Fate 

Submitted 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 sulfoxaflor 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 cotton 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 pollinatorattractive 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. PROBLEM FORMULATION

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 focuses 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 (USEPA 1998) and 

is consistent with procedures and methodology outlined in the Overview Document (USEPA 

2004). 

2.1 Nature of the Regulatory action 

The purpose of this assessment is to evaluate the environmental fate and ecological risks for the 

proposed new 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 environment. 

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 jeopardize 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 application as a liquid 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 okra, 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 target pests for watercress. Given the fact that 

watercress 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 subclasses of neonicotinoid insecticides include the cyanosubstituted (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. 2011). Sulfoxaflor has also not demonstrated crossresistance 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. 2011); this lack of cross resistance is believed to be partially 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 sulfoxaflor 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 

nitroguanidine-substituted neonicotinoids such as imidacloprid, acetamiprid and thiamethoxam 

are in subclass A.

2.2.3 Overview of Physicochemical, Fate, and Transport Properties 

Sulfoxaflor is characterized by a water solubility ranging from 550 to 1,380 ppm with low 

potential for volatilization from dry and wet surfaces. Partitioning coefficient of sulfoxaflor from 

octanol to water (Kow) suggests low potential for bioaccumulation in aquatic organisms 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 phosphor images for cotton 

from this study are shown in Figure 1. From zero to 72 hours, Panel A and B of Figure 1

indicate little movement of 14C-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 

localised (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/eClassification/
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 from 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 enters into plant tissue and is metabolized into X-474 and X061. Furthermore, sulfoxaflor reaching aquatic systems by drift is expected to degrade rather 

slowly.

2.2.4 Stressor Source, Intensity and Identity

Sulfoxaflor is formulated as a suspension concentrate (SC) and water dispersible granules 

(WDG) and is 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 maximum single 

rate of application for sulfoxaflor formulations ranges from 0.043 to 0.133 lb a.i/A with a

maximum yearly rates of 0.090 to 0.266 lb a.i/A/year applied in two or three applications at

intervals ranging from 5 to 14 days. 
16

In characterizing the 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 intensity 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 source 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 chemicals are expected to reach. These processes include run-off, 

leaching and spray drift. Partitioning of sulfoxaflor to air is not expected to be important 

due to the low vapor pressure and Henry’s Law constant for sulfoxaflor. Exposure in 

surface water results from drifted parent as only minor amounts is expected to run-off 

only when rainfall and/or irrigation immediately follow application. For the degradate XPlant Foliage: Parent (major)

Application of Sulfoxaflor Parent

Drift

Direct 

Aquatic Systems: Parent (major) Application

Wash-off

Slow Aerobic/Anaerobic Aquatic 

Degradation Soil System: Parent (major)

Expected soil concentration following: Fast 

degradation of parent and slow degradation 

of X-474 in the soil system

Parent (major)

(The major undegraded amounts + 

Minor amounts from 

run-off

X-474 (major)

(The minor 

amounts from 

parent degradation) 

+ Major amounts 

from Run-off

Run-off Parent (minor)

X-474 (major) Run-off

X-540 (minor)

(From run-off 

only)

X-540 (minor)

Surface Water Ground Water

Leaching

Run-off
17

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.

In terrestrial 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.

Sulfoxaflor 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, organisms are expected to be exposed to 

parent sulfoxaflor and the degradation products X-474 and X-540 (Figure 2). 

Comparative 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 (LC50 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 

degradates to aquatic organisms. Toxicity data for mammals and birds indicate that X474 is less acutely toxic compared to parent sulfoxaflor, while the minor degradate, X540, is about 2X more acutely toxic than parent based on mammalian acute LD50 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 details). 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 as 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 lower 
18

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 values 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 proposed 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, worms, 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 species, 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 pesticide 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 of 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 pesticides 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 Sulfoxaflor to Non-target Organisms

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

Birds1

Mallard duck (Anas platyrhynchos)

Bobwhite quail (Colinus virginianus)

Zebra finch (Poephila guttata)

Practically non-toxic

Slightly toxic

Moderately toxic

Mammals Laboratory rat (Rattus norvegicus) Slightly toxic
19

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

Insects Honey bee (Apis mellifera L.)

Bumble bee (Bombus terrestris)

Very highly toxic

Moderately toxic

Freshwater fish2

Bluegill sunfish (Lepomis macrochirus)

Rainbow trout (Oncorhynchus mykiss)

Carp (Cyprinus carpio)

Practically non-toxic

Freshwater invertebrates Water flea (Daphnia magna) Practically non-toxic

Estuarine/marine fish Sheepshead minnow (Cyprinodon 

variegatus) Practically non-toxic

Estuarine/marine 

invertebrates

Mysid shrimp (Americamysis bahia)

Eastern oyster (Crassostrea virginica)

Highly toxic

Practically-non toxic 1 In absence of data, 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 bodies 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 marine 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 source, 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 

process 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 the 

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 

consumption 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 determine 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 concern 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 via 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

Figure 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 2
22

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

Ingestion
23

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 foliar 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, (including 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 queens rely 

solely on royal jelly. 

** interception of spray droplets is also a potential route of exposure during mating and orientation flights

Wax, Propolis
24

2.7 Analysis Plan 

2.7.1 Methods for Conducting Ecological 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 (USEPA, 2004). 

The RQ is the risk value for the screening-level assessment 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 (LD50), medial lethal 

concentration to 50% of tested organisms (LC50), the no observed adverse effect level 

(NOAEL)3, and the no observed adverse effect concentration (NOAEC). The resulting ratio of 

the point estimate of exposure 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 corresponding 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 

following 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 estimates 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 (USEPA, 2004). Generally, 

aquatic exposure estimates are generated from EPA models and incorporate maximum proposed 

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 agricultural fields. Aquatic exposure 

concentrations, for all crops except watercress, in this assessment were based on EECs calculated 

using Tier II-linked Pesticide Root Zone Model (version 3.12.2 Carousel 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; Fletcher 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 Terrestrial Exposure (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 (upper-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.htm 

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 Assessment4. Tier 1 of this draft 

framework involves estimating pesticide doses to honey bees from direct contact using an upperbound estimate of 2.7 μg 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 laboratory conditions. Measures of effect are based on deleterious 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 adverse 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 tenuous at best. Commonly used 

laboratory-derived toxicity values include estimates of acute mortality (e.g., LD50, LC50) 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 level 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.html
27

Table 3. Summary of assessment and measurement endpoints for Sulfoxaflor

Assessment Endpoint Measures of Exposure Measures of Effect

1. Abundance (i.e., survival, 

reproduction, and growth) of 

individuals and populations of 

birds2

.

Maximum (peak) 

residues on food items 

(foliar)

1a. Zebra finch and mallard duck acute 

oral LD50.

1b. Mallard duck subacute dietary LC50.

1c. Mallard duck and bobwhite quail 

chronic reproduction NOAEC and 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 

LD50.

2b. Laboratory rat 2-generation 

reproduction chronic NOAEL and LOAEL.

3. Survival and reproduction of 

individuals and communities of 

freshwater fish3 and 

invertebrates.

Peak EEC (acute), 21-d & 

60-d surface water EEC 

(chronic)1

3a. Rainbow trout, bluegill sunfish and 

carp acute LC50.

3b. Fathead minnow early life stage 

NOAEC and LOAEC.

3c. Daphnid acute EC50.

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 LC50.

4b. Saltwater mysid acute LC50.

5. Survival of individuals and 

communities of freshwater and 

estuarine/marine benthic 

organisms.

21-d pore water and 

sediment EEC1

5a. Freshwater midge subchronic NOAEC 

and LOAEC.

5b. Estuarine/marine mollusk acute EC50

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 seedling 

emergence and vegetative vigor EC25

values.

7. Maintenance and growth of 

individuals and populations of 

aquatic vascular and nonvascular 

plants.

Peak surface water EEC 7a. Lemna gibba acute EC50 values based 

on yield and growth rate.

7b. Algal acute EC50 values based on cell 

density, biomass and growth rate.

8. Population size and stability of 

managed bee colonies; Quality of 

hive products

Upper bound oral and 

contact dose to adult 

and larvae (laboratory 

studies)

8a. Honey bee adult acute contact LD50.

8b. Honey bee adult acute oral LC50.

8c. Honey bee larval chronic NOAEC or 

LD10

8d. Honey bee colony level effects
28

Assessment Endpoint Measures of Exposure Measures of Effect

LD50 = Lethal dose to 50% of the test population; NOAEC = No-observed-adverse-effect level; LOAEC = 

Lowest-observed-adverse-effect level; LC50 = Lethal concentration to 50% of the test population; EC50/EC25

= 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 surrogates 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. ANALYSIS

3.1 Use Characterization 

Sulfoxaflor is proposed 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 uses include 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 (herbaceous 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 is formulated as a 

suspension concentrate “SC” (Proposed label: GF-2032 SC containing 2 lb a.i/gal) and 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 liquid 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 acreages 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-commercial ornamentals (ground application)*

Crop/Crop Group**

Crop Group(CG) Or 

Subgroup (SG)

Max Single 

Rate (lb a.i./A)

Max No. of 

Applications

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 & Pistachio 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 7
30

Crop/Crop Group**

Crop Group(CG) Or 

Subgroup (SG)

Max Single 

Rate (lb a.i./A)

Max No. of 

Applications

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 for 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 Transport Characterization 

3.2.1.1 Physical and chemical properties

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

indicate that the chemical is characterized by a water solubility ranging from 550 to 1,380 ppm 

in alkaline to acidic conditions, respectively. 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 m3 mole-1, respectively at 25 °C). Partitioning coefficient of sulfoxaflor from octanol to 

water (Kow) suggests low potential for bioaccumulation in aquatic organisms such as fish. 

However, the logarithm of its portioning coefficient from octanol to air (Log Koa=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 half-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 Koc.

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 C10H10F3N3OS

CAS number 946578-00-3

PC code 005210

Molecular Weight 277.27 g/mol
31

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 10-11atm

25°C → ≤ 1.9 x 10-8 torr; ≤ 2.5 x 10-6 Pa; ≤ 2.5 x 10-11atm

X-474

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

478320-06 

478320-22 for X-474

Henry’s Law Constant (@ 20 & 

25 C)

6.7 x 10-12 atm m3 mole-1; 5.1 x 10-9 torr m3 mole-1

1.2 x 10-11 atm m3 mole-1; 9.1 x 10-9 torr m3 mole-1

478320-07 from VP at 20°C

Calculated from VP at 25°C

Half-life in Air (t1⁄2 in hours) range: 7.8 - 15.5 

EPI-Suit v3.2 (AOPWIN) & 

Level III Fugacity Model

Log Koa 10.11 EPI-Suit v3.2 (KOAWIN)

Kow @ 20 C & pH 7

Parent: 6 (Log Kow = 0.802)

X-474, X-540 and X-457: <2 (Log Kow = 0.3)

478320-11

478320-20/24/27

Koc 7 – 74 mL/g

3.2.1.2 Fate and Transport Properties

The fate and transport behaviour of Sulfoxaflor had 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

F3C

* denotes position of radiolabel in the pyridine ring

14C-Sulfoxaflor (or XDE-2208)

Figure 6. Radiolabeled sulfoxaflor used in fate and transport studies

Sulfoxaflor consists of two diastereomers in a ratio of approximately 50:50. Each of the 

diastereomers consists of two enantiomers that cannot be resolved using conventional (nonchiral) 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 stable in acidic/neutral/alkaline sterilized aqueous buffered 

solutions (pH values of 5, 7 and 9; MRID 47832-149). In addition, parent 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 soil surfaces (MRID 478320-21). 

Table 6. Fate properties of sulfoxaflor parent and its major degradate X-474 in abiotic 

systems

Property Description or Value & Other Relevant Information 

Reference

(MRID)

Hydrolysis half-life 

@ 25 °C

Parent: 

Stable in sterile aqueous buffered solution at pH values of 5, 7 

and 9

478321-49

X474 degradate (no study; results inferred from the dark 

controls of the aqueous photolysis study (MRID 478322-83):

Stable in sterile aqueous buffered solution 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-061 [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 are 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 halflife Stable 478320-21
33

b) Biotic Degradation

The fate properties of sulfoxaflor 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 products 

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 biodegrade 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 systems 

is X-474. Under anaerobic soil conditions, the parent compound was metabolized with half-lives 

of 113 to 120 days while under anaerobic aquatic conditions the chemical was more persistent 

with half-lives of 103 to 382 days.

In contrast to its short-lived 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 CO2 or the formation of other minor degradates. 

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 

Parent t1⁄2 X-464 t1⁄2 (MRID)

Aerobic Soil Metabolism (days): 

25 °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 Metabolism (days): EU 

Soils incubated for 4 months at 20 °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 10 °C/40% WHC <1 184 478320-13

Aerobic Soil Metabolism (days): 

Aberford Series (Site J1), Rutland, UK : L; EU 

Soil sterilized/incubated for 4 months at 20 °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 @ 

25 °C/35% of the WHC

NC NC

Anaerobic phase (days) NC 320 478322-79

Soil Metabolism: Aerobic Phase (days) Aberford Series (Site J1), Rutland, UK : L; 2 hrs 

under aerobic conditions & 120 d under anaerobic 

conditions @ 25 °C/40% of the WHC

NC NC

Anaerobic phase (days) NC 532 478320-13

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 @ 20 °C 88 NC 478320-14
34

Property Soil or Water/Sediment System*

Half-life & (Fitting Equation)

Reference 

Parent t1⁄2 X-464 t1⁄2 (MRID)

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%) incubated for 103 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%) incubated 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 while 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 System Parent Degradation Products (% of Applied)

Reference 

(MRID)

Aerobic Soil 

Metabolism 

US soils @ 

25 °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): None; Mineralization (MRL):

CO2 (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 @

20 °C/ 40% 

of the WHC

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: CO2

(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 @ 10 °C/ 40% of the 

WHC

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

termination); 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: CO2 (max. 6% @ termination; NER: max. 9% @ termination 478320-13

Aerobic Soil 

Metabolism

Aberford Series (Site J1), 

UK sterilized then 

incubated @ 20 °C/ 40% of 

the WHC

MAJ: X-474 (max. 83% after 90 days then declined to 77% @ termination); 

MIN: None; MRL: CO2 (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: CO2 (max. 0.45% @ termination); NER:

max. 25% @ termination 478322-79
35

N

S

N O

F3C

NH2

O

N

S

NH O

F3C N

S

O O

F3C

Property Soil or Water/Sediment System 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: CO2 (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: CO2: 

max. 0.6 to1.5%, in systems 1 and 2, respectively, 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: None; MIN: X-474 (max. 3% @ 14days in systems-3 and max. 8% 

@ study termination in system-4 (other replicate was only 3%); MRL: CO2: 

<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 both of these 

degradates are persistent (90th percentile half-lives were 526 days (range 96 to 670 days) for X-457 and 2,808 days 

(range 71 to 3,630 days) for X-540

Rapid Bio-degradation 

(90th percentile t1⁄2= 0.4 days)

(Aerobic Soil System)

Slow Aqueous Photolysis

(t1/2= 261 days)

Very Slow Aqueous Photolysis

(Practically Stable) Sulfoxaflor 

Parent

X117210-61 (X-061)

X117189-22

X-474

X-540 X-457

Very Slow Biodegradation*

(90th percentile t1⁄2= 825 

days)

(Aerobic Soil System)
36

Figure 7. Expected environmental degradation pathways and transformation 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 biotic and 

biotic systems.

Table 9. Selected environmental degradates 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 C10H12F3N3O2S

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 C9H14F3N2OS

Common Name X11519540 (X-540)

IUPAC

5-(1-methanesulfonyl-ethyl)-2-trifluoromethylpyridine

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

Molecular Weight 253.24 g/mole

Molecular 

Formula C9H10F3NSO2

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 C8H8F3NO

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 C8H6F3NO

c) Field Dissipation in Terrestrial Systems

N

S

N O

F3C

NH2

O

N

S

NH O

F3C

N

S

O O

F3C

F3C N

OH

F3C N

O
37

Extensive data were collected from the terrestrial field dissipation (TFD) studies for sulfoxaflor 

(MRID 47832282). Complete analysis of the data is included in Appendix A and hereunder is a 

summary of these data. The terrestrial field dissipation (TFD) study for sulfoxaflor 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 (X540 and X-457). Adsorption/desorption 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. Therefore, 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 California (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 rates ranging from 100g a.i./ha (equivalent to 0.089 lb a.i/A) to 200 

g a.i./ha. 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 collection 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 precipitation 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 soil 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 shaker 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 analyzed directly. Soil and 

water samples were analyzed for sulfoxaflor and its aerobic soil metabolite (X-474, X-540 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 samples were spiked at 1x and 40x the LOQ (0.05 ng/mL). Spiked samples 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% for X-457, 

and 81.0 and 111% for X-540. Recovery in transit stability pore water samples was 88 % for 
38

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 various 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 limits of Detection/Quantification LOD/

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 zero-time concentrations.

A summary of the TFD Half-lives for parent 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 

CALIFORNIA* 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 X474 as its concentration 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 especially if 

leaching is limited (concentrations ranging from 1 to 18% of the applied parent were left in the 

soil after a year). Dissipation half-lives (DT50) 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 

the 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 49 62 217 40 248 109 51 58

0-36” (entire 

profile) 6 10 49 60 200 36 114 59 45 52

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

Data 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 1st 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 1st

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 1st application. At ON (Canada) 

site, it reached 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 1st 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 1st application. Observed data confirm that field dissipation of X474, from the top soil, is mainly related to transport (Koc= 7 to 74 mL/g) rather than degradation.

Other Degradates: X-540 and X-457 were minor transformation products in the field. In most 

field sites, the two degradates dissipated from the 0-6 inch soil layer 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 high persistence of its most probable parent (the major degradate X-474). A 

kinetic analysis was not performed for X-540 and X-457.

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

transformation product X-474, 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 of residues 

in target and rotational crops and summary/analysis of this data are included in Appendix A.

Top soil carryover is not expected for sulfoxaflor parent but is expected for X-474, X-457 and X540. Estimated 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 X457, the maximum top soil carryover is estimated to be <2% in FL, ND, 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 (Kfoc 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 for 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 its degradates

Soil: Geographic Location

Kfoc For

Parent & Degradates L/Kg 1

T; S; Si & C=

Texture; Sand; Silt & Clay 2

pH

% 

Parent X-74 X-57 X-40 T S% Si% C% OC CEC

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, USA 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, Spain 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 (Kfoc; 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 sulfoxaflor and transformation products 

were not subjected to the desorption step. Freundlich desorption isotherms (Kf) ranged from 0.18 

to 0.89 (Kfoc of 9-61 suggesting that parent sulfoxaflor will not bind irreversibly and that some 

material will desorb from the 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 0.001 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 (without 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 classifications 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 47832270). 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 Information 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 

considered 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), and 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. The method was validated over a concentration range of 

0.050-50.0 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 method 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) Metabolism, Distribution and Expression of Residues in Plants

Sulfoxaflor is a systemic pesticide; therefore it is important to analyze available plant data 

toward understanding how exposure pathways may be affected by plants. A study was 

conducted, on tomato plants, where 14C sulfoxaflor was foliarly applied in one experiment and 

was soil applied in another6. 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, 

14C-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 degradates in parallel from parent and in sequence from 

parent to X-474 to X-061. 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-061 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 1st/2nd/Last Application; DAL= days after last application

Chemical source: Foliar= from Foliar applied parent; Soil= from Soil applied parent

Residues in plants

Residues in fruits

% of 

Applied

% of 

Applied

Not Shown: 

<1% of -40 

plus -57 

Degradates
44

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 entered the 

plant from foliage and was subjected to plant metabolism producing degradates X-474 and X061. Therefore, both of these degradates can be considered as plant metabolism degradates.

In contrast to foliage, the majority of the radioactive residues in the tomatoes proper were

identified as the degradate X-474 followed by substantially lower concentrations of parent and 

X-061 (Figure 8). The noticeable increase of X-474 in tomato foliage suggests the presence 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 also appear to move into the plant via root 

uptake, plant metabolism (reducing 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-474 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 peas7

, three foliar applications, a 

total of 601 g a.i./ha; and two soil applications, totaling 434 g a.i./ha), lettuce (MRID ?8

, three 

foliar, one on immature plants and two on mature plants, totaling 599 g a.i./ha along with one 

soil application at a rate of 454 g a.i./ha ) and rice9

, three foliar application, totaling 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 Hastings, 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 Residue 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 & 

Tomato

Immature Tomato & 

Peas

Immture Rice

Mature Lettuce

Mature Tomato & Rice

Mature Peas

Tomato Fruits & Rice 

Grain

Peas 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, only 

limited sulfoxaflor parent enters the plant before it degrades 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 originated parent sulfoxaflor” that 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 

Applied
46

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 parent with relatively 

higher concentrations. Plant metabolism of foliage or soil originated parent and degradate X-474 

appears to be occurring at all stages of plant development producing X-061 and other degradates. 

The pattern of formation and decline for parent 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 sulfoxaflor 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 incorporated in the 

plant foliage with only limited degradation. It appears that this is the main source of the 

insecticide sulfoxaflor that would kill sap sucking insects. This is because washed-off 

sulfoxaflor, that reaches the soil system, is expected to degrade rapidly to the main degradate X474 (aerobic soil 90%tile t1⁄2= 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 foliage of growing crops that depends

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 terrestrial 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.

Sulfoxaflor 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 that the degradate X474 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 low concentrations of X-540 and X-457.

h) Fish Bioconcentration

No Fish bioconcentration study was submitted due to the low Kow (Kow @ 20 C & pH 7= 6; Log 

Kow = 0.802). Based on the low Kow, sulfoxaflor is not expected to bioaccumulate in aquatic 

systems. Although the parent compound has a high KOA which signifies a potential for 

bioaccumulation in terrestrial ecosystems, sulfoxaflor is not expected to 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 sulfoxaflor 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 pond 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, 

there 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 scenario. 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 has 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 these 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 

parent sulfoxaflor which represent the stressor of concern in aquatic systems. Based on the 

toxicity of parent sulfoxaflor and important degradates, i.e., X-474 and X-540 to aquatic 

organisms, only parent and X-540 are considered in estimating the EECs of the stressor. 

However exposure is dominated by the degradate X-474 and in 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 estimated 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 representing 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 Interest and Parent (all Crops Except Watercress)

a. Inputs Used for Modeling 
48

The first set of input parameters needed for modeling is labeled application parameters for 

various use patterns. Currently suggested labeled application parameters for sulfoxaflor are 

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 ornamentals)

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 crops:

from date of 

seedling to 

pre-harvest 

taking into 

consideratio

n the preharvest 

interval 

(PHI) for 

each crop 

PHI ranges 

from 1 to 14 

days)

For trees:

from Prebloom 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 ground; 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 from 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 chosen 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 to 
49

represent labeled 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 modeling

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

Berries 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 MSsoybeanSTD 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 7
50

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 NJmelonSTD 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 FLpeppersSTD 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& Rutabaga 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 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

* Scenarios with irrigation

** including: Broccoli, Brussels sprouts, Cabbage, Cauliflower, Kale

The third set of input parameters needed for modeling is the fate and transport characteristics of 

the chemicals 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-m3 

mol-1 @ 25 oC) 1.2 x 10-11 (for both) Calculated
51

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 Water (t1⁄2 in 

days @ pH 7) Stable (for both)

Because the only photolysis degradate is included

(MRID 478322-83) 

Aerobic Soil Metabolism 

(90th % t1⁄2 in days) 1,502 (0.4) (MRIDs 478655-78 and 478320-13)

Hydrolysis (90th % t1⁄2 in 

days) Stable (for both)

(MRID 478321-49) 

All degradates are considered stable

Aerobic Aquatic 

Metabolism (90th % Whole 

system t1⁄2 in days) 1,577 (141) (MRID 478320-14)

Anaerobic Aquatic 

Metabolism (90th % Whole 

system t1⁄2 in days) 873 (672) (MRID 478322-77)

Koc (Average in L/Kg) 14 (35)

(MRID 478320-14)

Use Koc for X-540

Chemical Application 

Method (CAM) 2

Parameter Guidance10

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 Using EXPRESS

Model runs were executed to determine if ground application gives higher EECs than aerial 

application. As expected, aerial application gave higher EECs compared to ground application, 

therefore modeling concentrated on aerial application and the results for ground application are 

not included in this assessment. 

The results 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 minus 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 only 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

60

Parent

X-474

X-540

TTR

Parent

X-474

X-540

TTR

Parent

X-474X-540

TTR

Cotton (NC) Citrus (FL) Fruits (All-CA)

EECs (ppb)

Crop

Drift

Run-off

0

10

20

30

40

50

60

Parent

X-474X-540

TTR

Parent

X-474X-540

TTR

Parent

X-474X-540

TTR

Cotton (NC) Citrus (FL) Fruits (All-CA)

EECs (ppb)

Crop

Drift

Run-off

0

10

20

30

40

50

60

Parent

X-474X-540

TTR

Parent

X-474X-540

TTR

Parent

X-474X-540

TTR

Cotton (NC) Citrus (FL) Fruits (All-CA)

EECs (ppb)

Crop

Drift

Run-off
53

(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-540 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 are 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 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 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 4.46 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 GAOnion_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 NCsweetpotatoSTD 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 1.99
54

Vegetables: 

Leafy except 

Brassica CG-4

Lettuce/Celery/ 

Spinach CAlettuceSTD 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 NCsweetpotatoSTD 26m08 3.21 3.21 3.20

a) Estimation of Sediment Concentrations

Exposure 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 deep12. The Agency does 

not currently have a methodology for exposure assessment for crops cultivated in flowing water.

In this assessment, conservative EECs resulting from application of sulfoxaflor to watercress 

were quantitatively obtained using Tier 1 Rice Model. It is noted however, that conservatism in 

the estimates comes from two assumptions:

(1) The 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; and

(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 intercepted 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) Leafy CG-5

Broccoli, Brussels 

sprouts, Cabbage, 

Cauliflower, Kale FLcabbageSTD 06m05 1.15 1.14 1.13
55

reapplication interval. Other input parameters, for the Tier 1 Rice Model include the average Koc

(30 L/Kg for parent).

In modeling, parent sulfoxaflor was considered 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 278 ppb of the TTR which 

would be parent sulfoxaflor alone because X-540 is not expected to form in aquatic systems. For 

a single application, the EEC is 93 ppb TTR while it is 186 ppb TTR following two applications.

These initial concentrations estimated by the Tier 1 Rice model assume sulfoxaflor 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 (Kd = 0.3 L/Kg calculated by the mode from Koc 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 assumes 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, EECs in surface water outside the rice paddy are expected to be affected by many 

factors. These factors and their impact on modeled EECs 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 reduce 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 the 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 Tier 1 Rice Model (i.e., EECs

in the rice paddy) is expected to be reduced by degradation. The impact of degradation on the 

TTR 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 persistence of parent in water/sediment 

system (90th % t1⁄2= 141 days). The effect of degradation 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 3rd application

EEC after the 1st application

EEC after the 2nd application
57

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

In Figure 12, the initial EEC value for one application (93 ppb of the TTR) may be reduced by 

degradation to 15 ppb within a one-year period. The initial EEC value after two applications (184

ppb of the TTR) may be reduced by degradation to 162.6 ppb within a one-year period. 

Similarly, the initial EEC value following three applications (275 ppb of the TTR) 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 and 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 sulfoxaflor depending on the flow rate of the stream (in 

miles/hour and in feet/second).

 13 http://hypertextbook.com/facts/2006/NervanaGaballa.shtml
58

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 suggests that a combination of application efficiency, pesticide 

degradation and stream flow are expected to produce surface water concentration values lower 

than the conservative values of 93 to 264 ppb.

(4) Impact of Agronomic Practices

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

(a) Expected usage or acreage that may be treated with the chemical. The EECs from Tier 1 

Rice Model are not adjusted for percent crop area (PCA). Lower EECs are expected as a 

result of such an adjustment due 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 the 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 applied 
59

(b) Known agronomic practices in “commercially grown watercress” are different from those 

assumed for rice. These practices include15:

• Use of flow-through irrigation: water flows through from the top of the crop 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 is 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 surface 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 sulfoxaflor 

to the EECs (i.e., reducing surface water contamination with the stressor “parent sulfoxaflor” as 

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, surface 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 pesticide 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 no data were identified to provide information on aquatic 

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 active ingredients. These exposures 

 15 Information is taken from a presentation to EPA by B&W of Florida, a commercial watercress 

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 assumption that organisms are exposed to a single pesticide residue in a 

given exposure scenario. 

3.2.3.1 . Terrestrial Vertebrate Exposure Modeling 

For sulfoxaflor spray applications, estimation of pesticide concentrations in wildlife food items 

focuses on quantifying possible dietary ingestion of residues on vegetative matter and insects. As 

described earlier, the EFED terrestrial exposure model T-REX (version 1.5.1) is used to estimate 

exposures and risks to avian and mammalian species. Input values used 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 Sulfoxaflor 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, an abundance of residue-decline data 

was 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 sets 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. R2 values (ln concentration vs. time) of 0.7 or higher

4. Statistical significance of regression coefficient of 0.1 or lower

Based on these criteria, a total of 44 foliar DT50 values were available for sulfoxaflor (Appendix 

B). These DT50 values consisted of measurements 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 DT50 values were averaged. The 

resulting 25 DT50 values averaged within a crop matrix are shown in Figure 14. These foliar 

DT50 values ranged from 1.8 to 29, with a calculated 90th percentile DT50 of 12.3 days based on 

log transformed values. 

 16 http://www.epa.gov/oppefed1/models/terrestrial/trex/t_rex_user_guide.htm
61

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 DT50

values, with residues measured in fruits and seeds/grains generally having the longest DT50

values. With one exception, average crop matrix DT50 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. Experimental 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 EC25 estimates, 

i.e., the EC25 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 the 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 10 100

Cumulative Frequency (%)

DT50 (days)

foliage

fruit

heads

roots

seeds/grain

Min=1.8

Max = 29

90th=12.3
62

4. ECOLOGICAL EFFECTS CHARACTERIZATION 

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-submitted studies that describe acute and chronic effects toxicity information 

for various aquatic and terrestrial animals and plants. A summary of the results of the registrantsubmitted toxicity studies used to characterize effects for this risk assessment is provided 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 aquatic 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 organisms 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 were with TGAI; no

technical end product (TEP) data were submitted with aquatic organisms.

Table 22. Summary of sulfoxaflor toxicological endpoints for aquatic organisms

Taxa Species Tested Toxicity 

Exposure(1)

Toxicological Endpoint 

(mg a.i./L)

MRID

(Classification)

Freshwater Fish

Rainbow trout 

 (Oncorhynchus mykiss)

Common carp

 (Cyprinus carpio)

Bluegill sunfish

 (Lepomis macrochirus)

Acute 

LC50 (96-hr): >387

LC50 (96-hr): >402

LC50 (96-hr): >363

47832111 

(Acceptable)

47832113

(Acceptable)

4783212

(Supplemental)

Rainbow trout 

 (Oncorhynchus mykiss)

Acute 

(X11719474) LC50 (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 

 (Daphnia magna)

Acute EC50 (48-hr): >400 47832114

(Acceptable)

Acute 

(X11719474) EC50 (48-hr): >205 47832106(Acceptable)

Chronic NOAEC (21-day): 50.5

(reduced reproduction)

47832127

(Acceptable)

Marine/Estuarine 

Fish

Sheepshead minnow 

(Cyprinodon variegatus) Acute LC50 (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 LC50 (96-hr): 0.64 47832117

(Acceptable)

Chronic NOAEC: 0.11

(time to first brood)

47832128

(Acceptable)

Eastern oyster 

 (Crassostrea virginica) Acute EC50 (96-hr): 86.5 47832115(Acceptable)

Freshwater 

Benthic 

Invertebrates

Midge 

 (Chironomus dilutus) Subchronic

NOAEC (10-d): 0.099 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) Chronic 

NOAEC (28-d): 0.037 mg 

a.i/L pore water 

(emergence)

NOAEC (28-d): 0.05 mg 

a.i/kg dry sediment

(emergence)

Gerke A (2009)

(Supplemental)

Aquatic Nonvascular Plants

Freshwater diatom 

 (Navicula pelliculosa)

EC50 (96-h): 81.2 

(Biomass)

NOAEC (96-h): 3.54 

(R,Y,B) (2)

47832123

(Acceptable)

Green alga

 (Pseudokirchneriella 

subcapitata)

EC50 (96-h): >101 (R,Y,B)

NOAEC (96-h): 101 (R,Y,B)

47832121

(Acceptable)

Bluegreen alga

 (Anabaena flos-aquae)

EC50 (72-h): 83.8 (Y) 

NOAEC (72-h): 12.0 

(G,Y,B)

47832124

(Supplemental)

Marine diatom 

(Skeletonema costatum)

EC50 (96-h): >103 (R,Y,B)

NOAEC (96-h): 103 (R,Y,B)

47832122 

(Supplemental)

Aquatic Vascular Duckweed

 (Lemna gibba)

EC50 (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 shown 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 LC50

values of >400 mg 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 test 
64

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 an estuarine/marine sheepshead minnow (Cyprinodon 

variegatus; MRID 47832110), sulfoxaflor was also practically non-toxic with an LC50 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 nontoxic to rainbow trout on an acute exposure basis (96-h LC50 >500 mg a.i./L; MRID 47832105).

4.1.2 Chronic 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 success, 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 

were 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 saltwater species (mysid shrimp, A.

bahia; MRID 47832117 and Eastern oyster, Crassostrea virginica; MRID 47832115). For D. 

magna, the 48-h EC50 is >400 mg a.i./L, the highest concentration tested . For Eastern oyster, 

new shell growth was significantly reduced at 120 mg a.i./L (75% reduction relative to control). 

The 96-h EC50 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 

water column only exposures, with a 96-h LC50 of 0.67 mg a.i./L. The primary degradate of 

sulfoxaflor (X474) is also classified as practically non-toxic to D. magna (EC50 >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, 

the test substance was stable and the mean-measured concentrations approximated the nominal 

concentrations (100-101% of nominal); therefore, 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 in 
65

the 100 mg a.i./L test 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 100 

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 (F0) and first generation (F1), reproduction rate of F0

(number of young), length of the surviving F0 and F1, and days to first brood by F0 were used to 

determine the toxicity endpoints. Complete F0 mortality (100%) was observed at the highest test 

concentration of 1.0 mg a.i./L within 7 days; no treatment-related effects on F0/F1 mortality, F0

reproduction rate, or F0/F1 length were observed at the lower test concentrations, which is 

somewhat unexpected given the reported acute LC50 0f 0.67 mg a.i./L described previously. The 

days to first brood by F0 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. No significant effects 

on days to first brood by F0 were observed at the lower test concentrations. The 28-day NOAEC 

and LOAEC were determined to be 0.11 mg and 0.25 mg a.i./L, respectively.

Although the chemical properties of sulfoxaflor (i.e., low Kow, low partitioning to solids) would 

not result in a requirement for submitting sediment toxicity testing, the subchronic toxicity of 

sulfoxaflor to benthic invertebrates via sediment exposure was investigated for larvae of 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 subacute exposure to C14-labeled sulfoxaflor administered in spiked sediments, 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 TRR 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 0.049 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. riparius) in whole sediment was 

determined using spiked water dosing. Midges 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. Emergence, development rate and survival were used to 

determine the toxicity endpoints. The 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 sediment 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 0.0949 
66

mg TRR/L (mean: 70%) relative to controls (mean: 91%). No treatment-related effects on 

development rate were observed. The 28-day NOAEC was determined to be 0.046 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 nonvascular plant is the freshwater diatom, Navicula pelliculosa, with a 96-h EC50 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 EC50 for frond count, 

dry weight and growth rate of >100 mg a.i./L (MRID 47832125) with no significant adverse 

effects on these endpoints observed at any treatment concentration. 

4.2 Terrestrial Effects 

A summary of toxicological endpoints for terrestrial organisms exposed to sulfoxaflor is 

provided in Table 23. 

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

Taxa Species Type of Toxicity

(Purity)(1) Toxicological Endpoint MRID

Birds

Bobwhite Quail

(Colinus virginianus) Acute (oral)

(95.6%; TGAI)

LD50: 676 mg/kg bw 47832101

(Acceptable)

Zebra finch

(Poephila guttata) LD50: >80 mg/kg bw 47832072

(Supplemental)

Bobwhite Quail

(Colinus virginianus)

Acute (oral) 

X11719474 (99.5%)

LD50: > 2,250 mg/kg bw 47832073

(Acceptable)

Bobwhite Quail

(Colinus virginianus) Subacute (dietary)

(95.6%; TGAI)

LC50(5-d): > 5,620 ppm 47832074

(Acceptable)

Mallard duck 

(Anas 

platyrhynchus)

LC50(5-d): >5,620 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

(Acceptable)

Mammals

Rat

(Rattus norvegicus) Acute (oral)

(95.6%; TGAI)

LD50 1000 mg ai/kg bw 

(female)

47832144

(Acceptable)

Mouse

(Mus musculus) LD50 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%) LD50 >2000 mg ai/kg bw 47832505

(Acceptable)

Acute (oral) GF-2032 

TEP (22%) LD50 >5000 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)

47832142

(Acceptable)

Terrestrial 

Invertebrates 

Honey bee, adult 

(Apis mellifera)

Acute (contact) TGAI LD50 (72-h): 0.379 ug 

a.i./bee

47832102

(Acceptable)

Acute (contact) TEP: 

GF-2032-SC

LD50 (48-h): 0.130 ug 

a.i./bee

47832419

(Acceptable)

Acute (contact) TEP: 

GF-2372-WG

LD50 (48-h): 0.224 ug 

a.i./bee

47832511

(Acceptable)

Acute (oral) TGAI LD50 (48-h): 0.146 ug 

a.i./bee

47832103

(Acceptable)

Acute (oral) TEP: GF2032-SCLD50 (48-h): 0.052 ug 

a.i./bee

47832417

(Acceptable)

Acute (oral) 

X11719474

LD50 (96-h): >100 ug 

a.i./bee

47832107

(Acceptable)

Acute (oral) 

X11721061

LD50 (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

(Supplemental)

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)

LD50 (72-h): 7.55 μg 

a.i./bee

47832418

(Supplemental)

Acute (oral) (TEP: GF2032-SC)LD50 (72-h): 0.027 μg 

a.i./bee

47832418

(Supplemental)

Terrestrial 

plants Multiple species

Tier 1 – Seedling 

Emergence (TEP: GF2032-SC)

EC25 (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

Terrestrial 

plants Multiple species

Tier 1/2 – Vegetative 

Vigor (TEP: GF-2032-

SC)

EC25 (21-d): > 0.178 lb

ai/A (>200 g ai/ha)

NOAEC = 0.178 lb 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 LD50 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 LD50 could not be determined 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 doses. 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 

at 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 LD50 to estimated to be >80 mg a.i./kg 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 LD50 would be somewhere between 80 

and 132 mg a.i./kg bw (20% and 70% regurgitation).

On a subacute, dietary exposure basis, sulfoxaflor is classified as practically nontoxic to birds, 

with 5-d LC50 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 LD50 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 concentration 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 Development (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 

LD50 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 animals 
69

survived, 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 fecal output, eyelids partially closed (ptosis), hair standing up (piloerection), labored 

respiration, soiling, increased salivation, increased lacrimation, lack of coordination, 

hypersensitivity to stimuli, , and decreased responsiveness to touch. Mortality was observed at 

≥1000 mg/kg bw. The male and female acute LD50 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 series 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 included muscle 

twitches, tremors, and convulsions, increased reactivity to stimuli, and increased responsiveness 

to touch. No gross internal findings were observed at necropsy. The oral LD50 was determined 

to be 750 mg a.i./kg bw. 

The acute, oral toxicity of 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 doses. Rats exposed to GF-2372 showed sublethal effects including facial staining, anogenital 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 

body 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 morphology, 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. Reproductive 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 F1 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 effects 

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 systemic 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 100 ppm (6.07 mg/kg/day). 
70

4.2.3 Toxicity to Bees

Sulfoxaflor is considered highly toxic to the honeybee, Apis mellifera, with an acute contact 

LD50 value of 0.379 μg ai/bee (TGAI; MRID 47832102) and 0.130 μg ai/bee (formulated 

product GF-2032-SC; MRID 47832419). Sulfoxaflor was also highly toxic on an acute oral 

basis (LD50 value of 0.146 μg ai/bee (TGAI, MRID 47832103) and 0.052 μg 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 LD50 of >100 

ug/bee (MRID 47832107). Based 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 (LD50 of 7.55 μg ai/bee, MRID 

47832418) compared to 0.130 μg ai/bee for the honeybee). 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 LD50 of 0.027 μg ai/bee; MRID 47832511 and 48-h LD50 of 

0.052 μg 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. RISK CHARACTERIZATION

Risk characterization provides the final step in the risk assessment process. In this step, 

exposure and effects characterization 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 Exposure and Effects Data 

As discussed in the problem formulation, risk characterization integrates EECs and toxicity 

estimates and evaluates the likelihood of adverse ecological effects to non-target species. For 

sulfoxaflor, 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 values 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 nontarget organisms and the need to consider regulatory action. LOC exceedence 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 - potential 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/LC50 or EC50 0.5

Acute Restricted Use EEC/LC50 or EC50 0.1

Acute Endangered Species EEC/LC50 or EC50 0.05

Chronic Risk EEC/NOAEC 1

Table 25. Risk Presumptions for Terrestrial Vertebrate Animals

Risk Presumption RQ LOC

Acute Risk Diet-based EEC/LC50 or Dose-based EEC/LD50 0.5

Acute Restricted Use Diet-based EEC/LC50 or Dose-based EEC/LD50 (or LD50 < 50 

mg/kg) 0.2

Acute Endangered Species Diet-based EEC/LC50 or Dose-based EEC/LD50 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) / LD50 (adult contact)

EEC (adult or larvae oral) / LD50 (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 2012).

Table 27. Risk Presumptions for Plants

Risk Presumption RQ LOC

Terrestrial Plants in Terrestrial and Semi-Aquatic Areas:

Non-Endangered Species EEC(1)/EC25 1

Endangered Species EEC/EC05 or NOAEC 1

Aquatic Plants:

Non-Endangered Species EEC(2)/EC50 1

Endangered Species EEC/EC05 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 

EECs determined from all 51 crop exposure scenarios 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 acute 
73

or chronic risk LOC, then RQ values re-calculated using 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 fish 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 listed 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 EEC1

(mg/L)

60-day 

EEC1

(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 / LC50 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)

Maximum 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 

Invertebrates 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 0.084 0.001 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 freshwater and saltwater invertebrates are based on the peak EEC / LC50 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 residues 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. Acute risk quotients for saltwater invertebrates 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: Brassica 

(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

Vegetables: Root & 

tuber

Potatoes, Turnip& 

Rutabaga MEpotatoSTD 2.5 0.004

Vegetables: Root & 

tuber Sweet Potatoes NCsweetpotatoSTD 4.2 0.007 1 EECs are based on total toxic residues of concern (parent + X-540; see Table 17). 2

Acute RQ values for saltwater invertebrates are based on the peak EEC / LC50 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 endpoint 

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 (acute FW & SW, chronic SW) are identical to those 

described earlier in Table 29. For fresh water benthic invertebrates, a slight exceedance 

(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 freshwater and saltwater benthic 

invertebrates based on total residues of interest

Use 

Category

Crop 

Scenario

Peak Pore 

Water EEC 1

(mg/L)

21-day Pore

Water EEC1

(mg/L)

Acute RQ 2, 3 Chronic RQ 3, 4

FW SW FW SW

Cotton NC Cotton 0.051 0.050 <0.0001 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 freshwater and saltwater invertebrates are based on the peak pore water EEC / 

EC50 values of >400 mg ai/L (Daphnia magna) and an LC50 value of 0.64 mg ai/L (mysid shrimp), respectively 

(see Table 22) 3

Chronic RQ values for freshwater and saltwater benthic invertebrates are based on the 21-d average pore 

water EEC / 28-d NOAEC values of 0.037 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 the 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 

concern (parent and X-540). Those RQ values that exceeded the acute risk to listed species 

LOCs and chronic risk LOCs are provided in Table 32. These refined RQ values are well below 

acute and chronic risk LOCs for non-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

NCsweetpotato

STD 3.21 0.005 3.21 0.09
76

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 saltwater invertebrates are based on the peak pore water EEC / LC50 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 EEC / 28-d 

NOAEC values of 0.037 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 EECs 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 Listed

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

RQ values for non-listed and listed non-vascular aquatic plants are based on the peak surface water EEC / 

EC50 value of >95.6 mg ai/L and a 96-h NOAEC of 3.54 mg ai/L, respectively (freshwater diatom, Navicula 

pelliculosa; see Table 22) 3

RQ values for non-listed and listed vascular aquatic plants are based on the peak surface water EEC / 7-d EC50

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 Terrestrial 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 

mammalian and avian size classes, and 3) various dietary categories being consumed. Chemicalspecific 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 TREX:

• 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, soybeans, 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 0.133 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. Acute Risk to Mammals 

Acute mammalian RQ values are calculated using the rat acute oral toxicity data (LD50 =1000 

mg/kg b.w.) adjusted for differences in body weight for a small (15g), medium (35g) and large 

(1000g) mammal by T-REX (adjusted LD50 =2198, 1778, and 769 mg/kg b.w., respectively) and 

the modeled acute dose-based EECs for various use scenarios and diet categories. Results from

the application scenario providing the highest residues on forage items (Citrus, Fruits-Pome, 

Fruits-Stone, Ornamentals, Tree nuts, Turf grass) are provided in Table 34. These results are 

based on the 90th 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 for mammals

Size 

Class

(g)

Adjusted

LD50

(mg/kgbw)

EECs (mg a.i./kg bw) and RQs1,2

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, Fruits-Pome, Fruits-Stone, Ornamentals, Tree nuts, Turf grass

15 2198 51.0 0.02 23.2 0.01 28.7 0.01 3.2 0.00 20.0 <0.01 0.71 <0.01

35 1778 35.2 0.02 16.1 0.01 19.8 0.01 2.2 0.00 13.8 <0.01 0.49 <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 dietarybased RQ values range from 0.03 (Fruits, pods, seeds, large insects) to 0.5 (short grass). Since 

these chronic RQ values are all 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 quotients for mammals

NOAEC 

(ppm in 

diet)

EECs (ppm diet) and RQs1,2

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 / NOAEC 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 NOAEL 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 bw/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 the potential for chronic 

risks to mammals is identified for all crop scenarios for at least one dietary category (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 RQs1,2

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, 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.-Fruiting, 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 Interval 

(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, Grains)

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 0.01
79

Size 

Class

(g)

Adjusted

NOAEL (mg 

a.i./kg

bw/d)

EECs (mg a.i./kg bw/d) and RQs1,2

Short Grass Tall Grass Broadleaf Plants 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-specific 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 

(LD50 > 80 mg a.i./kg bw; MRID 47832072) which reflects the concentration above which dosedependent 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 LD50 

values adjusted differences in body weight for birds (20, 100, 1000g) (adjusted LD50 =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 DT50 of 12.3 days. 

Avian acute RQs for sulfoxaflor are shown in Table 37. The overall range in acute RQ values is 

from <0.01 to 0.70, and the potential for acute risks to birds (including reptiles and terrestrialphase amphibians) is identified for all crop scenarios for at least one dietary category

Table 37. Acute dose-based risk quotients for birds

Size 

Class

(g)

Adjusted

LD50 (mg 

a.i./kgbw)

EECs (mg a.i./kg-bw) and RQs*

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, 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

LD50 (mg 

a.i./kgbw)

EECs (mg a.i./kg-bw) and RQs*

Short Grass Tall Grass Broadleaf 

Plants Fruits/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 <0.01

100 110 9.7 <0.09 4.5 <0.04 5.5 <0.05 0.61 <0.01 3.8 <0.03 0.14 <0.01

1000 155 4.4 <0.03 2.0 <0.01 2.5 <0.02 0.27 <0.00 1.7 <0.01 0.06 <0.01 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 80 mg a.i./kg bw for the zebra finch (MRID 

47832072)

RQ values shown in bold exceed the acute risk to listed species LOC of 0.1

Avian subacute dietary-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 

LC50 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

LC50

(ppm 

diet)

EECs (ppm in diet) and RQs1,2

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

5620 53.44 0.01 24.49 <0.01 30.06 0.01 3.34 <0.01 20.93 <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/subacute LC50 of 5,620 ppm diet for mallard (MRID 47832104)

Potential chronic effects to terrestrial birds (including 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 sulfoxaflorspecific 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 RQs1, 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 terrestrial 

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 

associated with foliar spray applications of pesticides (e.g., via ground and aerial methods) 

including systemic pesticides such as sulfoxaflor. This decision-making framework was recently 

presented and reviewed by a FIFRA Scientific Advisory Panel.

17 The overall proposed 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 conservative 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 none 

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 risks are identified in Tier I (i.e., 

where risk estimates exceed levels of concern18; 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 studies (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 tier 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 studies; 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 applications, 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 discussed 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 in 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., produce 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 intended 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 estimates 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 

controlled 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 or 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 which 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 Tiered Approach for Assessing Risk to Honey Bees from Foliar Spray 

Applications
84

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 μg 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 oral 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 applications

Life 

Stage Exposure Type Dose (μg a.i./beeper 1 lb a.i./A)(1)

Sulfoxaflor Dose for 

Max Application 

Rate (μg 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 0.72 2.8 n.a.

(1) Source: USEPA 2012. Draft Pollinator Risk Assessment Framework

(2) Based on a 48-h acute oral LD50 of 0.0515 ug ai/bee for GF-2032 (MRID 47832417) and acute contact 

LD50 of 0.130 ug ai/bee for GF-2032 (MRID 47832419).

(3) Bolded value exceeds 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 accomplished 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 48446601 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 materials 

from various field studies

Application 

Rate (lb ai/A)

Plant 

Pollen*

Plant 

Nectar

Plant 

Tissue

Forager 

Nectar*

Forager 

Pollen

Comb 

Pollen

Comb 

Larvae MRID

Cotton

1 x 0.045 1.26 0.13 0.22 0.03 <0.01

2 x 0.045 2.54 0.05 0.83 0.04 0.01 48755606

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 0.08
85

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 0.52b 0.05 0.29 48446601

1 x 0.043 1.48b 0.09 0.81

Phacelia

1 x 0.006 0.06a

48445806

1 x 0.012 0.04a

1 x 0.021 1.76b 0.61a

1 x 0.045 0.23a

1 x 0.088 1.01a

Pumpkin

1 x 0.022 0.08 0.03 0.20b 48755601

1 x 0.089 0.38 0.03 1.27b

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 caste and life stage of 

the bee. Consumption rates for different castes, life stages and tasks of honey bees have been 

recently reviewed and summarized 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, and 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 drone pollen and nectar 

consumption rates is used for calculating oral doses of sulfoxaflor. Feedback from the 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 doses of 

sulfoxaflor in royal jelly is not conducted because available 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 80
86

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 none 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 consumption 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 0.041 292

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 shown in Table 42 and Table 43, a total oral dose is estimated. 

This oral dose is then divided by the applicable acute oral LD50 (0.0515 μg ai/bee for adult 

workers and >0.2 μg 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, RQs 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 acute LD50 for adult (0.0515 μg ai/bee) and 

larval (>0.2 μg 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 the 
88

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 LD50 of 0.0515 μg a.i./bee and a consumption rate of 292 mg/d 

for 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 consumption rate among the various castes assessed. 

A comparison of each of the 88 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 0.07 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 15

Frequency

Ratio of Nectar Concentration to 0.07 ppm Threshold
89

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 characterizing 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 description also addresses 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. None of these RQ values exceed the applicable acute or chronic 

risk LOC. Specifically, 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 factor 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 relative 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, which 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 from 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)

SW Invert. 

RQ 

(benthic)

Acute <0.0001 0.0002 <0.0001 0.009 <0.0001 0.006

Chronic 0.08 0.04 0.001 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 these 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 concern (Table 33). This finding, combined with knowledge of the mode of action of 
90

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

Exposure

Avian Dose 

RQ

Avian Dietary 

RQ

Mammalian 

Dose RQ

Mammalian 

Dietary RQ

Acute <0.74 0.01 0.02 n/a

Chronic n/a 0.27 3.8 0.53

RQ values based on the maximum terrestrial EECs derived from 2 x 0.133 lb ai/A, 7 d 

interval exposure scenario; see Risk Estimation 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 potential 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 LD50 

because birds regurgitated the dose. Because this regurgitation followed a dose-dependent 

response (with 20%-100% of 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 actual exposure 

may be substantially lower and thus, the LD50 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 regurgitation was avoided would address this source of 

uncertainty in the avian acute risk estimation. In such a study, the acute oral LD50 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 chronic dose-based RQ values presented in 

Table 36, chronic risk concerns were identified for all of the proposed sulfoxaflor uses for at 
91

least one dietary category which comprises four separate pesticide application scenarios. 

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 the 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 which 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 affect 

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 individual (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 castes of bees modeled with the oral 

route of exposure (Table 44). Acute oral RQ values range from 0.8 to 5.7 across all castes of 

adult worker and larval bees examined. 

A number of uncertainties associated with the Tier 1 risk estimation for sulfoxaflor 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. LD50)

• accuracy of consumption rate estimates used for various bee castes

• variation in pesticide 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 sulfoxaflor in pollen and nectar

(6.6 and 1.0 ppm, respectively). These values were obtained from the cotton residue study using 
92

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 (Panel A), forager-collected pollen (Panel B), 

and forager-collected nectar (Panel C) over the 10-d residue collection period. 

For plant pollen, applications were made on Day 0 (all treatments) and Day 5 (three treatments). 

Residue data shown in Panel A of Figure 17 indicate a rapid decline in sulfoxaflor 

concentrations in cotton pollen immediately following pesticide applications. This steep decline 

may be related to cotton flowers remaining 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 represent 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 forager-collected 

pollen (Panel 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 maximum 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 magnitude greater than the next highest concentration measured in nectar. Results 

shown in Panel C of Figure 17 reflect mean values across two hives. Unexpectedly, this 

maximum concentration in nectar occurred in between 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 11

Sulfoxaflor 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 11

Mean 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

C
94

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” LD50 because 

mortality at the highest test concentration (45%) did not exceed 50%. Although use of this nondefinitive LD50 value introduces some uncertainty in the Tier 1 risk assessment, the close 

proximity of the mortality response (45%) to 50% suggests that the actual LD50 value would 

likely be relatively close to the 0.2 ug ai/bee value used in the assessment. The 7-d LD50 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 nectar 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 source 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 

concentrations 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 concentration 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 corresponding 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 introduces uncertainty in that reliability of scaling pesticide residues 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 reduce 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 total 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 functions 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 advantageous 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 with 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 these 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/A

Mean 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 ranging 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; 2011a,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 treatmentrelated 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 during 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 HechtRost (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 tunnel 

(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 June (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 US, it is noted that all but the 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 bee 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 the 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 rates during and after bee flight 

(Schmitzer 2010; 2011a,b), the magnitude of forager bee mortality was generally greater when 
97

pesticide was applied during bee flight compared to after bee flight, likely reflecting the 

combined effect of exposure via direct contact 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 

sulfoxaflor 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, they 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 sustained 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 Flight 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 were 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 foraging 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 the 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 for 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 only 7 and 9 days exposure, which is far short 

of the recommended duration of semi-field studies by OECD Guideline 75. A longer postexposure evaluation time is necessary in order to evaluate the effects over an entire honey bee 

brood cycle (21 days for workers). 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 by 
98

OECD Guideline 75), which may have confounded interpretation of brood development results 

as colony bees may have experienced 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-strength 

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 the 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 comprehensive evaluation of biological effects; rather it 

was designed to quantify sulfoxaflor residues in various plant matrices. Although pre- and postapplication assessments of brood can be compared (Table 47), it 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 observation 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 development 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 index 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) reported 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 by 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 rate 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 termination 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. 

Regardless of the source of the high brood termination rate 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 reference 
99

toxicant (fenoxycarb) for these two studies, which indicates that despite the high larval mortality 

in control hives, a major catastrophic impact on brood could be detected. Importantly, the 

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 to demonstrate that the study design was sufficient 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 Schmitzer (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 results 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 termination 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 study.

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 rates 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 was 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% reduction 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 rates 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 measurements 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 measurements 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 maximum US application rate of 2 x 0.134 lb ai/A. Although 
100

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 impacts 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 are 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 assessed 

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 one or more Tier 2 semi-field 

tunnel studies 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 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. 
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. Schmitzer (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: 

0.004, 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. 

Single 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, after flight: 

dermal, oral

During flight: Direct 

contact, dermal, oral

Pre-bloom, after flight: 

dermal, oral

Direct contact, dermal, 

oral

Direct contact, dermal, 

oral
102

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. Schmitzer (2011c)

(no MRID)

6. Ythier 2012

MRID 48755606

Exposure 

Duration, 

Month of Study 

Initiation 

In-Tunnel Exposure: 

(pre-application) 11d

(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, prebloom) 0d

(post-application, after 

& during flight) 7d

(post-application, prebloom) 10d

Post Tunnel Obs.: 

20d

June

In-Tunnel Exposure: 

(pre-application, after 

& during flight) 10d 

(pre-application, prebloom) 0d

(post-application, after 

& during flight) 7d

(post-application, prebloom) 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) 3d

(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**

Day 0: up to 4X ↑;

Day 1-7: treatments ≈ 

controls

Not assessed

Flight Intensity Day 0: up to 5X 

decrease (dosedependent)

Day 3-7: Doseindependent 

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 

Behavior

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 assessed
103

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. Schmitzer (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% doseindependent ↓ 

Not assessed Treat vs. Control: 

Up to 15-28% reduction 

in 48g ai/ha through 

27DAA (pre bloom) and 

15DAA (after flight)

Treat vs. Control: 

- treatments ≈ controls 

up through 60DAA

Treat vs. Control: 

- treatments > controls, 

but late season may 

have confounded 

results

- By D90AA, only 1/18 

colonies failed (8 g/ha)

Pre vs. Post Appl.

Hive strength similar 

across treatments 

before and 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 

controls (7DAA)

1. Long 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 

variability within 

treatments (n=3)

1. Poor control 

performance re: brood 

termination rate (65%) 

2. Long 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. Schmitzer (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%)

- colony strength: 

generally sustained 

reduction vs. controls

Fenoxycarb (300g /ha 

& Dimethoate 

600g/ha: 

- colony 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 (2012), 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 treatment 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 assessment, 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 Cosmetic 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 similar 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 the 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, sulfoxaflor 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 assessment considers broadly described taxonomic 

groups and so conservatively assumes that list species within those broad groups are collocated 
106

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 potential 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,” determination 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 indirect 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,” conclusion 

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 downwind 

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-listed 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 reptiles; 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 application 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 invertebrates
107

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 Assumptions, 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 limited 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 proposed 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 forces. 

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, maximum 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 surface 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 environments 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 conditions. 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 of 
108

uniform mixing does not account for stratification due to thermoclines (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: 20,000m3

. This 

ratio is recommended to maintain a sustainable constructed 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 standard 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 reflected 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 sufficient 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 relies 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 limitations 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 species 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 exposures, 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 incidental 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 the 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 and 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 finch) did not produce a definitive LD50 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 mammals, an LD50 of 1000

mg/kg bw was used (rat). Chronic NOAEC/NOAEL toxicity values used for birds and mammals 

are 200 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 assumption 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 

through 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 Phacelia. As noted 

previously, there are limitations in these data which contribute to uncertainty in the Tier 1 risk 

assessment for bees. Specifically, the pumpkin residue data reflect systemic transport only and 

were collected several days after pesticide application. The Phacelia 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) introduces 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 acute 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 of 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 current 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 

information 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 registration. 

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 nonstandard 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 mean 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 variability 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 

insufficient for concluding whether sulfoxaflor applications adversely impact brood 

development, even at the lower application rates 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 one 

or more Tier 2 semi-field tunnel studies conducted according to OECD 75 guidance. 

6. LITERATURE CITED

6.1 Environmental 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 and 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 Sediment 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. Report 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 XDE208 Soil Metabolites, Dow AgroSciences LLC. Report Number: 080161, Report Date: 4-Jan2010. 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. Balcer, 2009. Aerobic and Anaerobic Degradation of XDE-208 

in Four European Soils, Dow AgroSciences LLC. Report Number: 080129, Report Date: 8-Sep2009. 177 pages. 

MRID 47832279

M Simmonds, 2010, XDE-208: Degradation in One Soil under Anaerobic Conditions Following 

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 Degradation of XDE-208 

in Four European Soils, Dow AgroSciences LLC. Report Number: 080129, Report Date: 8-Sep2009. 177 pages. 
113

MRID 47832280

B. M. Wendelburg, 2010, Aerobic Soil Degradation Rate of X11579457 in 4 European Soils, 

Dow AgroSciences LLC. Report 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 47832282

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 Indianapolis 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 metabolites (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 submitted 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 spectrometry 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 its major metabolites in water using offline solid-phase extraction and liquid 

chromatography with tandem mass spectrometry detection; JRF America Study Number KP2010-08; Company Report Number 101650; GLP, unpublished study submitted by Dow 

AgroSciences.
114

MRID 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. Study 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 Number 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 Effects 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 test 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 080055 

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 1941488
115

MRID 4783212

Gerke A (2008). XDE-208: Acute toxicity test to the bluegill sunfish, Lepomis macrochirus, 

determined under static test conditions. ABC Laboratories 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 Laboratories 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 static 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 47832126
116

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 (2010). 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 the 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 Company 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 LC50 study with the northern 

bobwhite.

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 47832104
117

Hubbard PM, Martin KH, Beavers JB (2008). XDE-208: A dietary LC50 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, Wiescinski 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, Ablotny 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) Acute 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 Insect Ecotoxicity Studies

MRID 48446601
118

Liepold, K. (2011). 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 48445806

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. (2011c). Toxicity Testing of GF-2626 on Honey Bees (Apis mellifera L.) under SemiField Conditions - Tunnel Test . Dow Study 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 with 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). Laboratory 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 

honeybee, 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 Number 

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 080081 
119

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 Report 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. (2012). 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. (2011a). 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. (2011b). 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 

Burns, Lawrence, 1997. Exposure Analysis Modeling System (EXAMS): User Manual and 

System Documentation. Ecosystem Research Division, National Exposure Research 

Laboratory. U. S. Environmental Protection Agency, Athens, GA.
120

Crailsheim, K.; Hrassnigg, N.; Gmeinbauer, R.; Szolderits, M.J.; Schneider, L.H.W. and U. 

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 consumption 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, queen larvae and nurse honeybees. Apidologie, 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. Environ. 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 Quality 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 

termination rate in honeybee brood studies under semi-field conditions. International 

Commission For Plant-Bee Relationships Bee Protection Group 11th 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. 2003. 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.

Smith, R. 2012. Written personal communication with Rick Smith regarding cotton flower 

development. E-mail to Keith Sappington (USEPA, OPP, EFED) dated June 3, 2012.
121

U.S. EPA. 1998. Ecological Risk Assessment Guidelines. Office of Research and Development, 

National Center for Environmental Assessment. Washington, DC.

U.S. EPA. 2000. Methods for Measuring the Toxicity and Bioaccumulation of Sedimentassociated Contaminants with Freshwater Invertebrates Second Edition. EPA 600/R99/064. Office of Research and Development; Office of Water, Washington, DC.

U.S. EPA. 2004. U.S. Environmental Protection Agency. Overview of the Ecological Risk 

Assessment Process in the Office of Pesticide Programs, U.S. Environmental Protection 

Agency: Endangered and Threatened Species Effects Determinations. Office of 

Prevention, Pesticide, and Toxic Substances. January 23.

U.S. EPA. 2012. White Paper in Support of the Proposed Risk Assessment Process for Bees 

Submitted to the FIFRA Scientific Advisory Panel for Review and Comment September 

11 – 14, 2012. EPA Office of Pesticide Programs, Washington DC.; Pest Management 

Regulatory Agency, Health Canada, Ottawa; California Department of Pesticide 

Regulation, Sacramento. 

(http://www.epa.gov/oppfead1/cb/csb_page/updates/2012/sapmtg-sept.html) 

Winston, M. L. 1987. The Biology of the Honey Bee. Harvard University Press, Cambridge, MA. 

ISBN 0-674-07409-2.

Zhu, Y. et al. 2011. Discovery and Characterization of Sulfoxaflor, a Novel Insecticide Targeting 

Sap-Feeding Pests. J. Agr. Food Chem. 59, 2950–2957.