Document ID: EPA-HQ-OPP-2009-0364-0009
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2011-12-22T05:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                            WASHINGTON, D.C. 20460
                                       
                          OFFICE OF CHEMICAL SAFETY 
                           AND POLLUTION PREVENTION

                              Environmental Fate 
                        and Ecological Risk Assessment
                          for Fluopyram Registration

 

                                       
                                       
Fluopyram: (N-[2-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]ethyl]-2(trifluoromethyl)benzamide
                       (CAS 658066-35-4, PC code 080302)

                                       

Prepared by:
Mohammed A. Ruhman, Ph.D.
Amanda Solliday, M.S.

Reviewed by:
Keith Sappington, M.S.
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

Table of Contents

I.	Executive Summary	1
A.  Nature of Chemical Stressor	1
B.  Potential Risks to Non-target Organisms	1
C.  Conclusions - Exposure Characterization	8
E.  Conclusions - Effects Characterization	8
F.  Data Gaps and Uncertainties	8
1. Environmental Fate	8
2. Ecological Effects	9
II.	Problem Formulation	9
A.  Stressor Source and Distribution	9
1.  Source and Intensity	9
2.  Physicochemical, Fate, and Transport Properties	10
3.  Pesticide Type, Class, and Mode of Action	10
4.  Overview of Pesticide Usage	10
B.  Receptors	11
1.  Ecological Effects	11
a.  Aquatic Effects	13
b.  Terrestrial Effects	13
2.  Ecosystems at Risk	13
C.  Assessment Endpoints	13
D.  Conceptual Model	14
1.  Risk Hypotheses	14
2.  Diagram	15
Figure 1a The aquatic conceptual model for spray application of fluopyram to agricultural crops (dotted lines indicate unlikely routes of chemical dissipation).	16
Figure 1b The terrestrial conceptual model for spray application of fluopyram to agricultural crops (dotted lines indicate unlikely routes of chemical dissipation)	17
E.  Analysis Plan	17
1.  Methods for Conducting Ecological Risk Assessment and Identification of Data Gaps	17
2.  Measures to Evaluate Risk Hypotheses and Conceptual Model	18
a. Measures of Exposure	18
b. Measures of Effect	20
c. Measures of Ecosystem and Receptor Characteristics	20
III.	Analysis	22
A.  Use Characterization	22
B.  Exposure Characterization	24
1.  Environmental Fate and Transport Characterization	24
a. Abiotic Degradation	25
b. Biotic Degradation	26
c. Tranformation Profile	28
d. Mobility	30
2.  Measures of Aquatic Exposure	31
a. Application Methods	32
b. Label Application Rates and Intervals	32
c. Modeling Approach	34
d. Model Inputs	35
e. Aquatic EECs	35
g. Aquatic Exposure Monitoring (Field Data)	37
3.  Terrestrial Exposure Assessment	37
a. Terrestrial Animal Exposure Modeling- Spray Applications	38
b. Terrestrial Exposure Monitoring (Field Data)	40
4.  Non-Target Terrestrial Plant Exposure Assessment	40
C.  Ecological Effects Characterization	40
1.  Aquatic Effects	41
2.  Terrestrial Effects	51
IV.	Risk Characterization	61
A.  Risk Estimation - Integration of Exposure and Effects Data	61
1.  Non-target Aquatic Animals and Plants	61
a. Water Column Exposure: Acute and Chronic Risk to Animals	61
b. Sediment Exposure: Acute and Chronic Risk to Benthic Invertebrates	63
c.  Aquatic Plants	65
2.  Non-target Terrestrial Animals	66
a.  Spray Applications: Acute Risk to Birds and Mammals	66
b. Spray Applications: Chronic Risk to Birds and Mammals	66
3.  Non-target Terrestrial and Semi-Aquatic Plants	68
B.  Risk Description - Interpretation of Direct Effects	68
1.  Risks to Aquatic Organisms	68
a.  Aquatic Animals and Plants:  Water Column Exposure	69
b.  Aquatic Animals:  Sediment Exposure	72
3.  Risks to Terrestrial Organisms	72
a.  Spray Applications: Acute and Chronic Risk to Birds and Mammals	72
b.  Non-target Terrestrial Invertebrates	74
c.  Terrestrial Plants	75
4.  Review of Incident Data	76
5.  Threatened and Endangered Species Concerns	76
C.  Description of Assumptions, Limitations, Uncertainties, Strengths and Data Gaps	77
1.  Exposure for All Taxa	77
2.  Exposure for Aquatic Species	78
3.  Exposure for Terrestrial Species	79
a.  Location of Wildlife Species	83
b.  Routes of Exposure	83
c.  Incidental Pesticide Releases Associated with Use	84
d.  Residue Levels Selection	84
4.  Effects Assessment	84
a.  Age Class and Sensitivity of Effects Thresholds	87
b.  Lack of Effects Data for Amphibians and Reptiles	88
c.  Use of the Most Sensitive Species Tested	88
Environmental Fate Studies	89
B.  Ecological Effects Studies Submitted to EPA	91
C.  Open Literature and Government Reports	96

VI. Appendices

   A. Environmental Fate and Transport Data Summaries

   B. Aquatic Exposure PRZM/EXAMS Modeling and Ground Water Modeling
   C. Terrestrial Residue EXposure (T-REX; Version 1.4.1, October 2008) and TERR-PLANT models 
   D. List of Ecological Effects Data
   E. The Risk Quotient Method and Levels of Concern
   F. Detailed Risk Quotients
   G. Data Requirements
 
         I. Executive Summary
 
 A.  Nature of Chemical Stressor  
 
Fluopyram (N-[2-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]ethyl]-2(trifluoromethyl)benzamide; fluopyram; CAS 658066-35-4, PC code 080302) represents a new group of fungicide chemistry, pyridinyl-ethylbenzamides. The biochemical mode of action of this chemical involves the inhibition of the enzyme succinate dehydrogenase within the fungal mitochondrial respiratory chain, thus blocking electron transport. Other fungicides that share the same target site, or succinate dehydrogenase inhibitors (SDHIs), include boscalid and carboxin, among others (FRAC, 2009).

The registrant reported that fluopyram is a fungicide with penetrative and trans-laminar properties. The active substance is also trans-located by the xylem vascular system.

Current formulations for fluopyram include suspension concentrates for the chemical alone (41.5% a.i), or with other fungicides including: tebuconazole (17.6% with 17.6% fluopyram), trifloxystrobin (21.4% with 21.4% fluopyram), pyrimethanil (33.8% with 11.3% fluopyram), or prothioconazole (17.4% with 17.4% fluopyram).  Fluopyram and /or its mixtures is proposed for agricultural uses on apples, watermelons, selected dry beans, grapes (wine), peanuts, potatoes, strawberries, sugerbeet, and tree nuts. 
 
 Fluopyram is stable to hydrolysis and soil photolysis and highly persistent in both aerobic and anaerobic aquatic systems. Based on laboratory studies, degradates that are expected to form in the terrestrial environment were observed at low concentrations and are considered minor (<=1 to 4.2% of the applied). In aerobic aquatic and anaerobic aquatic metabolism studies, no degradates were observed. If these degradates do not form in the aquatic systems, then these compounds may reach these systems via run-off at low concentrations based on the level of formation in laboratory aerobic soil studies. Limited ecological effects data show low comparative toxicity of degradates compared to parent. One algal study with fluopyram-lactame and one dietary rat study with fluopyram-PCA have been submitted and no treatment-related effects were observed in either study. Therefore, based on the high persistence of fluopyram, the low occurrence of degradates and the low comparative toxicity of degradates, only the parent compound (fluopyram) was considered of concern in aquatic and terrestrial ecosystems.
 
 Fluopyram is stable to hydrolysis and soil photolysis and highly persistent in both aerobic and anaerobic aquatic systems. Based on the high persistence of fluopyram, the low occurrence of degradates and the low comparative toxicity of degradates, only the parent compound (fluopyram) is considered of concern in aquatic and terrestrial ecosystems.
 
 B.  Potential Risks to Non-target Organisms 
 This is the Environmental Fate and Effects Division's (EFED) national screening-level ecological risk assessment for the proposed registration of fluopyram.  Tables 1 and 2 summarize the major conclusions and uncertainties of this assessment for aquatic and terrestrial receptors, respectively. Functionally, the estimated risks may translate to reduced survival, growth and/or reproduction of impacted species.   
 
 The results of this screening-level risk assessment suggest the potential for chronic risk to non-target mammals, birds, reptiles and terrestrial-phase amphibians based on modeled exposure resulting from spray applications of fluopyram.  Low acute risk concerns exist for mammals, birds, reptiles and terrestrial-phase amphibians. Fluopyram shows low acute toxicity to terrestrial invertebrates on a mortality basis and some reproductive effects to this taxon were observed at high levels of fluopyram exposure. Overall risk to terrestrial plant species is low, but some uncertainty exists with the effects of fluopyram on the seedling emergence of one dicot species, buckwheat. The use of the fluopyram at proposed label rates presents low risk to all aquatic taxa, including freshwater fish and aquatic invertebrates, estuarine/marine fish and aquatic invertebrates, aquatic-phase amphibians, freshwater and estuarine/marine benthic invertebrates and aquatic vascular and non-vascular plants.
 
 For all risk calculations, the estimated environmental exposure concentrations of the fluopyram-only product are assumed to be equal or greater than the EECs of the proposed products containing fluopyram and another active ingreadient, based on the application rates in the proposed labels. Overall, the coformulations for all fluopyram products with dual active ingredients appear to have low acute toxicity to terrestrial organisms, but no avian data were submitted for any co-formulated product. In addition, only rat acute oral studies were submitted for pyrimethanil and prothioconazole coformulations. From the available toxicity data, it appears as if use of the fluopyram co-formulated products with tebuconazole, trifloxystrobin, pyrimethanil, and prothioconazole have a higher potential to adversely impact aquatic ecosystems than use of the proposed fluopyram-only product. 
         
 Table 1.  Summary of Environmental Risk Conclusions for Aquatic Organisms Exposed to Fluopyram
 Risk Conclusion
 Summarized Risk Characterization and Major Uncertainties
 Low acute and chronic risk for freshwater and estuarine/marine fish and invertebrates (water column)
 For acute risk to freshwater and estuarine/marine fish species, risk quotients were not calculated because the available toxicity endpoints were non-definitive (LC50 > highest test concentration). The peak estimated exposure concentration for aquatic organisms is more than two orders of magnitude less than the highest tested fluopyram technical concentrations in acute toxicity tests which caused no adverse effects to freshwater and estuarine/marine fish species. No mortality or sublethal effects were observed in acute fish studies with the fluopyram active ingredient. In studies with the fluopyram formulated product (fluopyram 500 SC, 41.5% active ingredient), sublethal effects included fish lying on the bottom of the test chamber, dark coloration, labored respiration, mucous secretion from intestine, surfacing, and lying on side/back. However, these effects were observed at much higher concentrations than is expected to occur in the environment.
 
 The level-of-concern for chronic risk to freshwater fish was not exceeded, based on the results of an early-life stage study. A chronic risk quotient was not calculated for estuarine/marine fish, because no chronic toxicity data were submitted for this taxon and appropriate acute-to-chronic ratios could not be determined due to lack of available data on definitive acute toxicity endpoints for any aquatic taxa. 
 
For acute risk to freshwater and estuarine/marine invertebrate species, risk quotients were not calculated because the available toxicity endpoints were non-definitive (LC50 > highest test concentration). However, the peak estimated exposure concentration for aquatic organisms is two orders of magnitude less than the lowest level at which immobility was observed in any aquatic invertebrate test. No other sublethal effects were noted in the submitted acute aquatic invertebrate studies. Therefore, acute risk to aquatic invertebrate species due to water column exposure appears to be low.
 
 The level-of-concern for chronic risk to aquatic organisms was not exceeded for freshwater invertebrates. No chronic data was submitted for estuarine/marine invertebrates. An acute-to-chronic ratio could not be calculated because no definitive acute endpoints were provided in any acute aquatic study. As an additional line of evidence to examine potential chronic effects to estuarine/marine invertebrates in the water column, the chronic water column estimated exposure concentration was compared to the available estuarine/marine benthic invertebrate NOAEC based on pore water concentrations. The potential chronic aquatic exposure level is approximately four orders of magnitude less than the level at which no adverse chronic effects were observed for estuarine/marine invertebrates. Based on the available information, the overall chronic risk to aquatic invertebrates appears to be low.
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 No studies were submitted to examine fluopyram chronic effects on estuarine/marine fish and estuarine/marine invertebrates in the water column. However, due to the low expected aquatic exposure concentrations and overall aquatic toxicity profile, additional data is not required.
 
 In the test conditions of the aquatic organism toxicity studies, the solubility of fluopyram technical appears to be much lower than that reported in the environmental fate information. However, the modeled potential exposure to aquatic ecosystems, utilizing the higher value for water solubility reported in the available fate information, is much lower than any of the levels at which effects were observed in the submitted aquatic organism toxicity tests.
 Low acute and chronic risk for freshwater and estuarine/marine benthic invertebrates
 No treatment-related effects on survival or growth occurred in a short-term 10-day study for estuarine/marine benthic invertebrates. Chronic data for both freshwater and estuarine/marine benthic invertebrates suggest adverse effects on reproductive, growth and development at high levels of fluopyram exposure. Estimated environmental exposure concentrations are much lower than the levels at which effects were observed in the submitted chronic sediment toxicity tests, and no levels-of-concern (LOCs) were exceeded for these taxa.
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 A short-term 10-day study with freshwater benthic invertebrates was not submitted for fluopyram. Due to the low estimated aquatic exposure concentrations and overall aquatic toxicity profile, additional data is not expected to change the risk conclusions. In addition, for persistent chemicals such as fluopyram, only chronic sediment toxicity tests are typically required.
 Low risk for aquatic vascular and non-vascular plants.
 No acute risk quotients for non-vascular or vascular aquatic plants exceeded any of the levels-of-concern (1.0) for the modeled crop use with the highest estimated exposure values (watermelon). Based on submitted algal studies, fluopyram showed similar toxicity whether the exposure was from the technical or end-use product. One algal study was submitted for the degradate fluopyram lactame, and no treatment-related effects were observed. Levels of concern were not exceeded for aquatic vascular or non-vascular plant species. 
 ---------------------------------------------------------------------------------------------------------
 
 
 
 Table 2.  Summary of Environmental Risk Conclusions for Terrestrial Organisms Exposed to Fluopyram
 Risk Conclusion 
 Summarized Risk Characterization and Major Uncertainties
 Low acute risk for birds
 
 Risk quotients were not calculated for acute risk to birds based on the non-definitive endpoints in the submitted acute and dietary studies (LD50 > 2000 mg ai/kg bw; LC50 > 4785 mg ai/kg bw). Less than 50% mortality occurred at the highest treatment level in all submitted avian acute oral and dietary studies. As a conservative assumption to approximate risk, the highest levels tested in acute oral and dietary studies were compared to the maximum acute dose and dietary-based EECs. All calculated ratios were < 0.1, the level-of-concern for listed species. Mortality and sublethal effects, such as soft excrement, fluffed feathers and a decrease in food consumption, were noted at all treatment levels in the most sensitive acute oral test with bobwhite quail. The lowest treatment level at which observations of mortality and sublethal effects occurred is approximately 4 to 71 times higher than the peak upper bound EECs of the highest fluopyram use scenario, depending on the dietary item and using the smallest size of the bird (most conservative) in the terrestrial exposure modeling. Therefore, overall acute risk to avian species appears to be low.
 
 Inhalation and drinking water exposure are not expected to be an appreciable route of acute exposure for birds.
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 In a limit acute oral test conducted with zebra finch, mortality was noted in the single treatment group (2000 mg ai/kg bw). A subsequent limit test was conducted with the same species, and no mortalities were observed at 2000 mg ai/kg bw. However, a definitive test is recommended if mortality occurs in a limit test (OCSPP 850.2100). Therefore, this study does not meet the data requirements for passerine species. 
 
 In an acute oral definitive test with bobwhite quail, mortality was observed at all treatment levels, but no LD50 endpoint was established as only 40% mortality occurred at the highest treatment level (2000 mg ai/kg bw). In the two submitted dietary studies with mallard duck and bobwhite quail, no mortalities were observed (LC50 > 4604 mg ai/kg diet and LC50 > 4785 mg ai/kg diet, respectively). Sublethal toxicity effects observed in all submitted studies include soft excrement, fluffed feathers, reduced vigilance, reduced food consumption and red pancreases noted during post-mortem examinations. Body weight reduction occurred in the highest treatment level in the dietary study with bobwhite quail, 4785 mg ai/kg diet. A NOAEL and NOAEC were not established due to observations of effects at the lowest treatment level in the most sensitive acute oral and dietary studies, both with bobwhite quail. Observations of a single mortality and reduced food consumption in the acute oral study at 500 mg ai/kg bw and reduced food consumption in dietary study at 279 mg ai/kg diet level. Therefore, some uncertainty exists in defining the lowest level at which mortality or sublethal effects would occur. 
 
 Based on the available information, risk to listed birds from acute exposure to fluopyram is not expected. A definitive acute LD50 endpoint has not been established for avian species. However, due to the overall low toxicity of fluopyram to avian species and relatively low exposure concentrations, a request for additional acute oral studies with bobwhite quail and a passerine species to define this endpoint is not recommended at this time.
 Chronic risk concerns exist for birds.
 Submitted fluopyram toxicity studies for avian species showed adverse effects such as reductions in hatchling body weight and survival, adult female body weight gain, numbers of eggs laid, embryo survival and egg shell thickness. For birds that consume short grass, tall grass, and broadleaf plants/small insects exposed to fluopyram via spray applications, dietary-based chronic RQs exceed levels-of-concern. One dietary item (seeds) did not result in chronic risk concerns.
 
 Exceedances of the chronic dietary levels-of-concern for this taxa occurred for all crops on the proposed label, with the exception of cherry. In addition, chronic exposure through drinking water is a concern for birds.
 ----------------------------------------------------------------------------------------------------------
 
 Low acute risk for mammals
 Results of oral, dermal and inhalation toxicity studies on rats show that fluopyram TGAI is practically non-toxic to mammals on an acute basis (LD50 > 2000 mg a.i./kg bw for both oral and dermal exposure routes and acute 4-hour LC50 > 2.091 mg/L and 5.1 mg/L in the two rat inhalation studies). The highest fluopyram concentration in the acute oral study with rats did not result in any mortality or sublethal effects and is approximately 20 times greater than the highest EEC predicted for the most conservative use scenario. Therefore, acute dose-based risk to mammalian species is presumed to be low.
 
 Inhalation and drinking water exposure are not expected to be an appreciable route of acute exposure for mammals.
 ----------------------------------------------------------------------------------------------------------
 No mammalian toxicity data was available for formulated fluopyram 500 SC.
 Chronic risk concerns exist for mammals.
 For the maximum application scenario considered in this risk assessment, dietary-based and dose-based RQs for chronic risk to mammalian species are above the chronic risk level-of-concern for three of the four dietary items (short grass, tall grass and broadleaf plants/small insects, with the exception of seeds). Exceedances of the chronic levels-of-concern for this taxa occurred for all crops on the proposed label.
 
 Based on this analysis, the potential for chronic adverse affects to mammalian species could occur at environmentally-relevant exposure concentrations. These potential effects include decreased body weight in adults and offspring, as well as reduced food consumption.
 
 Based on a screening estimate, chronic exposure through drinking water is not expected to be a concern for mammals.
 ----------------------------------------------------------------------------------------------------------
 
 Risk concerns exist for terrestrial plants.
 For terrestrial plants, Tier I seedling emergence and vegetative vigor toxicity tests showed no detrimental effects >=25% in survival, dry weight or height compared to the controls for any test species except buckwheat. Because buckwheat showed a 50.4% reduction in dry weight at 0.444 lbs a.i./A (twice the proposed maximum application rate) in the seedling emergence test, a Tier II was conducted with this species. This test resulted in highly variable results for the most sensitive endpoint, biomass, and an EC25 and NOAEC could not be determined. 
 ----------------------------------------------------------------------------------------------------------
 Because uncertainty exists in determining the levels at which fluopyram may cause adverse effects to at least one species, buckwheat, and additional Tier II test is requested. In the absence of additional data, risk is presumed for some species of terrestrial plants.
 
 Low direct toxicity to beneficial non-target insects and other terrestrial invertebrates. Some reproductive effects observed at high exposure concentrations.
 Results of acute oral and contact toxicity studies with honey bees demonstrate that fluopyram technical and the formulated product show low direct toxicity to beneficial insects. Additional toxicity studies were submitted for other nontarget terrestrial invertebrates, such as the rove beetle (Aleochara bilineata), predatory mite (Typhlodromus pyri), springtail, (Folsomia candida), parasitic wasp, Aphidius rhopalosiphi, soil mite (Hypoaspis aculeifer) and earthworm (Eisenia fetida). No definitive acute toxicity endpoints were provided for honeybees or other nontarget terrestrial invertebrates, due to lack of 50% mortality or more in any of the toxicity tests (at levels greater than >83.2 ug a.i./bee, the maximum application rate, or observed soil concentrations following fluopyram application at twice the maximum proposed label rate, depending on the exposure units measured in the toxicity study). Therefore, acute toxicity to these additional nontarget terrestrial invertebrates appears to be low, based on mortality.
 
 In submitted reproduction studies with soil-dwelling invertebrates, reductions in the number of surviving offspring were observed at nominal concentrations of 5.81 mg a.i./kg dw soil and greater in the 28-day study conducted with earthworms, and at nominal concentrations of 207.5 mg a.i./kg dw soil and greater in the 28-day study conducted with springtail. No reproductive effects were observed in studies with any studies with other terrestrial invertebrate species.
 

 
 			
 								
 
 C.  Conclusions - Exposure Characterization  
 
 Fluopyram has low vapor pressure/Henry's Law constant (2.33x10[-8] torr/2.94 x 10[-10] atm m[3] mole[-1]) and its solubility in water is 16 ppm.  Fluopyram is stable to hydrolysis and soil photolysis; highly persistent in aerobic/anaerobic aquatic systems (90[th] % t(1/2) ranges from 1,360 to 1,757 days); relatively stable to aqueous photolysis (t(1/2)= 57 days), and persistence under aerobic soil conditions (90[th] percentile t(1/2)= 464 days).  In field studies, fluopyram has shown similar persistence in three out of five terrestrial field dissipation studies on bare-ground plots (dissipation half-lives ranged from 24 to 83 days in two studies in GA and ND and 163 to 539 days in three studies in WA, CA, and NY).  For mobility, fluopyram appears to have medium absorption affinity to soil and sediment particles rendering it to be moderately mobile in systems with varied textures and organic matter content (Koc ranges from 316 to 591 L/Kg).  The major routes of dissipation for fluopyram are bio-transformations in aerobic systems.  The high persistent and moderate mobility of fluopyram suggests that it may cause contaminate ground water.  Furthermore, fluopyram can reach surface water through erosion, drift and/or run-off events. 
 
 
 E.  Conclusions - Effects Characterization 
 
 Chronic effects were observed at environmentally-relevant concentrations for birds and mammals, based on modeled EECs that are the peak upper-bound estimates of exposure. Overall acute toxicity to avian species appears to be low, but some uncertainty exists in defining the LD50. Low acute toxicity was observed in the submitted studies for mammals and terrestrial invertebrates. For terrestrial plants, some adverse effects on dry weight were observed in terrestrial plant toxicity studies for one species, buckwheat. The variability in response of this species during the Tier II seedling emergence test did not allow reliable calculation of toxicity endpoints. Therefore, some uncertainty exists with the levels at which fluopyram may cause adverse effects to some species of plants. Acute and chronic toxicity of fluopyram to fish and aquatic water-column and benthic organisms is low. Acute toxicity to non-vascular and vascular aquatic plants is low. Fluopyram technical and the formulated product show similar toxicity based on studies conducted with terrestrial invertebrates, fish, aquatic invertebrates and algae. Limited ecological effects data show low comparative toxicity of degradates compared to parent.
 
 
 F.  Data Gaps and Uncertainties 
 
 	1. Environmental Fate  	
 
At this time, the screening level assessment for fluopyram has been conducted with only limited environmental fate and transport data gaps.  The assessment would have been strengthened if hydrolysis and aerobic soil studies were conducted on at least two of fluopyram degradates, namely Fluopyram-7-hydroxy and fluopyram pyridyl-carboxylic acid (Fluopyram-PCA).  This would have confirmed the suggested degradation pathway for fluopyram and collected data necessary for confirming conclusions on the degree of persistence for these degradates.
 
 	2. Ecological Effects 	 
 
 The screening level risk assessment for fluopyram has been conducted despite an unfulfilled guideline requirement. An additional Tier II seedling emergence study is requested for buckwheat (Fagopyrum esculentum). Table G-1 (Appendix G) lists the status of the ecological effects data requirements for fluopyram.  
 
  
         I. Problem Formulation
 
 A.  Stressor Source and Distribution  
 
 	 1.  Source and Intensity  
 
 Fluopyram is formulated as a suspension concentrate (SC) alone and mixed with four other fungicides: tebuconazole, trifloxystrobin, pyrimethanil, and prothioconazole.  These formulations are proposed to be applied as liquid spray to foliage using ground, airblast or aerial spray equipments. The rate of application for fluopyram formulations ranges from a maximum single rate of 0.092 lb a.i/A to 0.222 lb a.i/A with a maximum rate of 0.445 lb a.i/A/crop cycle and a range of 5 to 14 days between applications.  The range of application rates for fluopyram in mixtures is from a maximum single rate of 0.091 lb a.i/A to 0.222 lb a.i/A with a maximum rate of 0.445 lb a.i/A/crop cycle. For this risk assessment, EFED considered application rates for the mixtures when rates resulting from their application are either higher and/or applied differently than formulations containing fluopyram alone. The maximum numbers of applications were mostly not specified but were calculated from allowed maximum crop cycle rate and the maximum single rate.
 
 Fluopyram parent is considered to be the stressor that would result from the proposed application of the chemical and/or its mixtures to crops, as discussed further below.  Partitioning to the air is not expected to be important due to the low vapor pressure and Henry's Law constant for fluopyram. 
 
 The Agency does not routinely include, in its screening risk assessments, an evaluation of mixtures of active ingredients, either those mixtures of multiple active ingredients in product formulations or those in the applicator's tank. In the case of the product formulations of active ingredients, each active ingredient is subject to an individual risk assessment for regulatory decision regarding the active ingredient on a particular use site (US EPA, 2004). Nonetheless, the available effects data for the fluopyram products that are co-formulated with tebuconazole, trifloxystrobin, pyrimethanil, and prothioconazole are documented in the effects characterization of this risk assessment.
 
 
 	2.  Physicochemical, Fate, and Transport Properties  
 
Fluopyram is characterized by a water solubility of 16 ppm in acidic and alkaline conditions.  The chemical has a low potential for volatilization from dry and wet surfaces (vapor pressure= 2.33 x 10[-8] torr and Henry's Law constant= 2.94 x 10[-10] atm m[3] mole[-1], respectively at 25 °C). Therefore fluopyram has low potential to partition into the atmosphere.

 In the laboratory, fluopyram was stable to hydrolysis and photolysis and showed high persistence to photolysis in water. The same high persistence was observed in aerobic/anaerobic soil systems (90[th] percentile t(1/2)= 464 days in aerobic systems and stable in anaerobic systems) and in aerobic/anaerobic water/sediment systems (extrapolated t(1/2) ranged from 648 to 5,240 days). Due to persistence, degradation products observed in all systems in the laboratory were low in number and concentration and were not considered as part of the stressor. In the field, dissipation half-lives ranged from 24 to 83 days in two bare-ground soils in GA and ND and between 164 to 539 days in three bare-ground soils in WA, CA, and NY.  In these field studies, the transient transformation product 7-hydroxy which was observed at low concentrations (maximum of 3%) as was the case in the laboratory (maximum of 4%).  In contrast, the other two degradates (PCA and benzamide) reached higher concentrations (maximum of 16 and 19%, respectively) than the laboratory (maximums of 1% each) but maximums were followed by rapid decline suggesting non-persistence.
 
 	3.  Pesticide Type, Class, and Mode of Action 
 
Fluopyram represents a new group of fungicide chemistry (pyridinyl-ethylbenzamides). The biochemical mode of action involves the inhibition of the enzyme succinate dehydrogenase (complex II) within the fungal mitochondrial respiratory chain, thus blocking electron transport. Other fungicides that share the same target site (succinate dehydrogenase inhibitors or SDHIs) include boscalid and carboxin, among others (FRAC, 2009). As reported by the registrant, at the fungal cell level, fluopyram has an effect on several stages of the life cycle of the fungi including spore germination, germ tube elongation, mycelium growth and sporulation.
 
 	4.  Overview of Pesticide Usage 
 
Fluopyram is a new pesticide that is proposed to be used in the United States to prevent and/or control certain fungal diseases on some major crops and therefore is expected to be applied in most agricultural areas of the US.  Fluopyram is formulated as a suspension concentrate (SC) alone and mixed with four other fungicides: tebuconazole, trifloxystrobin, pyrimethanil, and prothioconazole.  Formulations are proposed to be applied by ground, airblast, and aerial spray into foliage (leaves, stems, and shoots), flowers and fruits. 
 
 B.  Receptors  
 
 	1.  Ecological Effects  
 
 Ecological measures of effect for this screening level risk assessment are based on a suite of registrant-submitted toxicity studies performed on a limited number of organisms in broad groupings.  Table 3 gives examples of taxonomic groups and test species evaluated for ecological effects in this screening level risk assessment.  Within each of these very broad taxonomic groups, an acute and/or chronic endpoint is selected from the available test data (see Table 4). A complete discussion of all toxicity data available for this risk assessment and the resulting measures of effect selected for each taxonomic group are included in Appendix D.  
 
 Table 3.  Taxonomic groups and test species evaluated for ecological effects in this screening-level risk assessment.
 Taxonomic group
 Representative species
 Birds [a]
 Mallard duck (Anas platyrhynchos)
 Bobwhite quail (Colinus virginianus)
 Zebra finch (Taeniopygia guttata)
 Mammals
 Laboratory rat (Rattus norvegicus)
 
 Terrestrial Invertebrates
 Honey bee (Apis mellifera)
 Freshwater fish [b]
 Bluegill sunfish (Lepomis macrochirus)
 Rainbow trout (Oncorhynchus mykiss)
 Fathead minnow (Pimephales promelas)
 Freshwater Invertebrates
 Water flea (Daphnia magna)
 Estuarine/marine Fish
 Sheepshead minnow (Cyprinodon variegatus)
 Estuarine/marine Mollusk
 Eastern oyster (Crassostrea virginica)
 Estuarine/marine Invertebrates
 Mysid (Americamysis bahia)
 Benthic Freshwater Invertebrates
 Midge (Chironomus tentans)
 Benthic Estuarine/Marine Invertebrates
 Amphipod (Leptocheirus plumulosus)
 Terrestrial Plants
 Monocots  -  corn (Zea mays), oat (Avena sativa), perennial ryegrass, (Lolium perenne), barley (Hordeum vulgare) and onion (Allium cepa) 
 
 Dicots  -  soybean (Glycine max), sugarbeet (Beta vulgaris), oilseed rape (Brassica napus), cucumber (Cucumis sativus), buckwheat (Fagopyrum esculentum) and sunflower (Helianthus annuus) 
 Aquatic Plants and Algae
 Duckweed (Lemna gibba) 
 Green algae (Pseudokirchneriella subcapitata)
 Blue-Green Algae (Anabaena flos-aquae)
 Freshwater Diatom (Navicula pelliculosa)
 Saltwater Diatom (Skeletonema costatum)
 [a] Birds may be surrogates for amphibians (terrestrial phase) and reptiles.
 [b] Freshwater fish may be surrogates for amphibians (aquatic phase).
 
 
For screening risk assessments, the following toxicity endpoints presented in Table 4 are used as inputs to the risk quotient (RQ) method for expressing risk (US EPA, 2004). The designation of "listed species" refers to either federally threatened or endangered species.
 Table 4.  Toxicity endpoints used in risk quotient calculations 
 Taxonomic group
 Representative species
Aquatic Animals
 Acute assessment 

Chronic assessment 

Lowest tested EC50 or LC50 for freshwater fish and invertebrates and estuarine/marine fish and invertebrates acute toxicity tests.

Lowest no-observed-adverse-effects- concentration (NOAEC) for freshwater fish and invertebrates and estuarine/marine fish and invertebrates early life-stage or full life-cycle tests.

Terrestrial Animals 
Acute avian assessment 

Chronic avian assessment 

Acute mammalian assessment 

Chronic mammalian assessment 
 

Lowest LD50 (single oral dose) and LC50 (subacute dietary).

Lowest NOAEC for 21-week avian reproduction test.

Lowest LD50 from single oral dose test. 

Lowest NOAEC for two-generation reproduction test or chronic dietary study
 
Plants
Terrestrial non-listed species 

Aquatic vascular and algae

Terrestrial listed species 

Lowest EC25 values from both seedling emergence and vegetative vigor for both monocots and dicots. 

Lowest EC50 for both vascular and algae.

Lowest EC5 or NOAEC for both seedling emergence and vegetative vigor for both monocots and dicots. 
 
 
 [a] Freshwater fish may be surrogates for amphibians (aquatic phase).
 [b] Birds may be surrogates for amphibians (terrestrial phase) and reptiles.
 
 		a.  Aquatic Effects 
 
 Acute and chronic laboratory and field tests on fluopyram provide information regarding lethality, as well as sublethal measures of effect.  Data are available on both the technical grade active ingredient (TGAI) and the typical end-use product (TEP) and corresponding effects on freshwater and saltwater fish, aquatic invertebrates, aquatic plants and algae. 

 		b.  Terrestrial Effects 
 
 For terrestrial effects, registrant-submitted studies on fluopyram technical are available for acute, subacute, and chronic exposure to birds, and acute and chronic exposure to mammals. Additional ecological effects data for fluopyram are available for honey bees (Apis mellifera) and other nontarget terrestrial invertebrates. Data are available on the toxicity of fluopyram formulations to the vegetative vigor and seedling emergence of terrestrial plants.
 
 	2.  Ecosystems at Risk  
 
 Ecosystems potentially at risk reflect a potential concern by the Agency and can be expressed in terms of the selected assessment endpoints.  The typical assessment endpoints for screening-level pesticide ecological risk assessments are reduced survival, growth and reproductive impairment for both aquatic and terrestrial animal species.  Potential effects on a set of surrogate species are used to extrapolate risk to all species.  For both aquatic and terrestrial animal species, direct acute and direct chronic effects are considered.  Although these endpoints are measured at the individual level, they provide insight about risks at higher levels of biological organization (such as populations and communities).  
 
 C.  Assessment Endpoints  
 
 This risk assessment considers the maximum application rate of fluopyram, the maximum number of applications, and the minimum application intervals as stated in the proposed labels to estimate exposure concentrations as a result of its proposed use.   This assessment is not intended to represent a site or time-specific analysis.  Instead, this assessment is intended to represent high-end exposures at a national level.  Likewise, the most sensitive toxicity endpoints are used from surrogate test species to estimate treatment-related direct effects on acute mortality and chronic reproductive, growth and survival assessment endpoints.    
 
 For plants in terrestrial and semi-aquatic environments, the screening assessment endpoint is the survival and growth of non-target species (crops and non-crop plant species).  Endpoints assessed include emergence of seedlings and vegetative vigor.  Although it is recognized that the endpoints of seedling emergence and vegetative vigor may not address all plant life cycle components, it is assumed that impacts at emergence and in active growth have the potential to impact individual competitive ability and reproductive success.  Data on the formulated product (as opposed to the active ingredient) are used to characterize potential effects on terrestrial plants.  
 
 For aquatic plants, the assessment endpoint is the maintenance and growth of standing crop or biomass.  Measurement endpoints for this assessment endpoint focus on algal and vascular plant growth rates and biomass measurements.
 
 The toxicity studies are used to evaluate the potential of fluopyram to cause adverse effects, to determine whether further testing is required, and to determine the need for precautionary label statements to minimize the potential adverse effects to non-target animals and plants (40 CFR §158.202, 2002).
 
 
 D.  Conceptual Model  
 
 	1.  Risk Hypotheses  

For fluopyram, the following ecological risk hypothesis is being employed for this risk assessment:
      
      Given the uses of fluopyram and its environmental fate properties, there is a likelihood of exposure to non-target terrestrial and aquatic organisms. 
            
      When used in accordance with the label, fluopyram results in potential adverse effects upon the survival, growth, and reproduction of non-target terrestrial and aquatic organisms.  
 
 In order for a chemical 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 exposure 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.  In addition, the potential mechanisms of transformation (i.e., which transformation products may form in the environment, in which media, and how much) must be understood, especially for a chemical whose metabolites/transformation products are of greater toxicological concern than the parent compound.  The assessment of ecological exposure pathways, therefore, includes an examination of the source and potential migration pathways for constituents, and the determination of potential exposure routes (e.g., ingestion, inhalation, and dermal absorption).
 
 Ecological receptors that may potentially be exposed to fluopyram and its transformation products include terrestrial and semi-aquatic wildlife (i.e., mammals, birds, amphibians, and reptiles), terrestrial and semi-aquatic plants, and soil invertebrates.  Aquatic receptors (e.g., freshwater and estuarine/marine fish and invertebrates, and amphibians) may also be exposed as a result of potential migration of fluopyram via spray drift and/or runoff/erosion from the site of application to various watersheds and other aquatic environments.  This information formed the basis for identifying potential endpoints, stressor, and ecological effects associated with uses of fluopyram.
 
 	2.  Diagram  
 
 Based on the preliminary iterative process of examining fate, transport 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 1.  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.  Sources of chemical contamination included spray drift and run-off and leaching to ground water is added given the persistence of parent fluopyram.
 
 
 Figure 1a The aquatic conceptual model for spray application of fluopyram to agricultural crops (dotted lines indicate unlikely routes of chemical dissipation).
 
 
 
 Figure 1b The terrestrial conceptual model for spray application of fluopyram to agricultural crops (dotted lines indicate unlikely routes of chemical dissipation).
 
 
 E.  Analysis Plan 
 
 	1.  Methods for Conducting Ecological Risk Assessment and Identification of Data Gaps 
 
 The primary method used to assess risk in this screening-level assessment is the risk quotient (RQ) and follows the methods outlined in the EPA Overview Document (EPA, 2004).  The RQ is the primary 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 LD50 or NOAEC. The resulting RQ is then compared to a specified level of concern (LOC), which represents a point of departure for concern. For example, if the RQ exceeds the LOC, then risks are triggered. In general, the higher the RQ, the more certain the potential risks. However, the risk quotients are not necessarily a true estimate of risk since there is no estimated probability of effect. Risk presumptions, along with the corresponding RQs and LOCs, are summarized in Appendix E.
 
 Generation of robust risk quotients is dependent on the quality of data from both fate and toxicological studies.  The adequacy of the submitted data is 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 fluopyram.
 
 For the ecological effects, Table G-1 (Appendix G) lists the status of ecological data requirements for fluopyram. An additional Tier II seedling emergence study is requested for buckwheat (Fagopyrum esculentum).
 
For fate and transport, Table G-2 (Appendix G) lists the status of fate and transport data requirements for fluopyram.  The adequacy of the submitted data was evaluated relative to Agency guidelines.  In this respect, it is noted that there were no hydrolysis and aerobic soil studies for two of the fluopyram degradates, namely Fluopyram-7-hydroxy and fluopyram pyridyl-carboxylic acid (Fluopyram-PCA). None existence of these data is not expected to affect this assessment which is based on the current conclusions about fate and transport of the chemical.
   

 

 
 	2.  Measures to Evaluate Risk Hypotheses and Conceptual Model  
 		
 		a. Measures of Exposure  
 
 Measures of exposure are estimates of exposure for a receptor determined by modeling or monitoring data.  Measures of exposure for fluopyram in this assessment are obtained from modeling efforts only, since this is a new chemical and national-scale monitoring data is not expected to be present.  Exposure models used for this assessment include the suite of standard exposure models commonly used in pesticide risk assessments (EPA, 2004).  Generally, aquatic exposure estimates are generated from EFED 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.
 
 
 
Exposure to aquatic organisms is assumed to occur through direct contact with ground water contaminated by leaching and surface water contaminated by drift and/or runoff/erosion from agricultural fields. Aquatic exposure concentrations for this assessment were based on EECs calculated using Tier II linked, Pesticide Root Zone Model PRZM (v3.12.2, May 2005) and EXAMS (v2.98.4.6, April, 2005).  PRZM/EXAMS are fate and transport simulation models coupled together with the input shell pe5.pl (August, 2007) to generate daily exposures and 1-in-10 year EECs. More information on these models can be found at http://www.epa.gov/oppefed1/models/water/index.htm.
 
 Measures of exposure for terrestrial mammals, birds, reptiles and amphibians similarly incorporate maximum proposed use rates but rely less on fate properties. Terrestrial exposures were estimated using a number of methods.  For fluopyram, acute and chronic terrestrial exposure estimates are derived directly from empirically determined observations of pesticide residues on various terrestrial food items.  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 residues on terrestrial food items.  The surface residue concentration (ppm) is estimated by multiplying the application rate (pounds active ingredient per acre) by a value specific to each food item. For numerous applications for a given use, the exposure model incorporates a first-order decay rate dependent on the foliar dissipation half-life of the chemical. In the absence of data, a default half-life of 35 days is used. In this assessment, the T-REX model was run for fluopyram uses (watermelon and strawberries) with the maximum proposed application rate (0.222 lb a.i./A), a maximum of 2 applications, and a 5-day application interval to screen risk to terrestrial organisms. The default foliar dissipation half-life was used for terrestrial exposure calculations, but some data were submitted by the registrant regarding the foliar dissipation half-life (see the Description of Assumptions, Limitations, Uncertainties, Strengths and Data Gaps section). Additional risk quotients for crop-specific application rates are presented in Appendix F. 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 1.4.1 (October 2008). For more details see Appendix C and the Exposure Characterization section of this document.
 
 TerrPlant is used by the Environmental Fate and Effects Division (EFED) as a Tier 1 model for screening level assessments of pesticides. The purpose of TerrPlant is to provide screening level estimates of exposure to terrestrial plants from single pesticide applications.  The model does not consider exposures to plants from multiple pesticide applications. TerrPlant derives pesticide EECs in runoff and in drift.  RQs are developed for non-listed and listed species of monocots and dicots inhabiting dry and semi-aquatic areas which are adjacent to treatment sites. A preliminary run of TERR-PLANT was conducted using the maximum application scenarios for ground application (labeled use rates for watermelon) and aerial application (labeled use rates for almond, pecan, pistachios and tree nuts). For more details see Appendix C and the Exposure Characterization section of this document.
 
Two screening tools were utilized to assess the potential for exposure to terrestrial organisms via inhalation and drinking water exposure. The potential for inhalation risk to birds and mammals was assessed using the Screening Tool for Inhalation Risk (STIR, version 1.0, November 2010). The STIR tool estimates spray droplet and vapor phase exposure using the physical properties of each chemical, application method and rate and then compares these exposure estimates to avian and mammalian toxicity data. The model estimates avian-inhalation toxicity values, when not directly available, from mammalian data by applying an adjustment factor representing the difference in lung tissue thickness and surface area between birds and mammals to the relationship between mammalian-oral, mammalian-inhalation, and avian-oral toxicity values to account for differences in avian and mammalian inhalation toxicity. The Screening Imbibition Program (SIP, version 1.0, July 2010) was used to upper-bound drinking water exposure potential using fluopyram's solubility, the most sensitive acute and chronic avian toxicity endpoints and the most sensitive acute and chronic mammalian toxicity endpoints.
 
 Additional information on the terrestrial exposure models and screening tools employed in this risk assessment can be found at http://www.epa.gov/oppefed1/models/terrestrial/.
 		
 		b. 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 may also be used to provide supporting lines of evidence for the risk characterization, monitoring data is lacking for this new chemical. Commonly used laboratory-derived toxicity values include estimates of acute mortality (such as LD50, LC50, or EC50) and estimates of effects due to longer term, chronic exposures (such as the NOAEC or NOAEL). In addition, effects other than survival, reproduction, and growth may be considered, (such as changes in biochemical, cellular, organ-level responses) but are typically used qualitatively  to characterize risks since, in many cases, the relationship between these effects and higher-order processes is highly uncertain. The latter can reflect changes seen in mortality, reproduction, or growth.  In general, for a given assessment endpoint, the lowest relevant measure of effect is used in calculating the risk quotient.  
  
 
 		c. Measures of Ecosystem and Receptor Characteristics  
 
 The assessment endpoints can be summarized as survival, growth, and reproduction of terrestrial and aquatic receptors to include birds, mammals, reptiles, amphibian, fish, terrestrial and aquatic invertebrates and terrestrial and aquatic plants. The response of these receptors to fluopyram exposure is represented by a small number of toxicity studies on representative or surrogate species.  Hence, there is considerable uncertainty regarding the response of a receptor since data for all species potentially exposed are not available.  The lowest available measure of effect for a given assessment endpoint is used to calculate risk to accommodate for some of this inherent uncertainty.  
 
 The ecosystems selected for modeling using PRZM/EXAMS aquatic assessment and T-REX for the terrestrial animal assessment are intended to be generally representative of any aquatic or terrestrial ecosystem associated with areas where fluopyram is used. The receptors addressed by the aquatic and terrestrial risk assessments for fluopyram are summarized in Table 3.  For aquatic assessments, generally fish and aquatic invertebrates in both freshwater and estuarine/marine environments are represented. For terrestrial assessments, three different size classes of small mammals are represented, along with five potential foraging categories (short grass, tall grass, broadleaf plants/small insects, fruits/pods/seeds/large insects, and seeds). For the three different size classes of small birds, four potential foraging categories are considered (short grass, tall grass, broadleaf plants/small insects, and fruits/pods/seeds/large insects).  For terrestrial plants, both dicots and monocots are represented by a variety of agricultural species.  In addition, data are available so that earthworms, terrestrial insects, and sediment-dwelling organisms are represented. Detailed information regarding the toxicity data available for these various classes of aquatic and terrestrial receptors is provided in the Ecological Effects Characterization section and in Appendix D.
         I. Analysis
 
 A.  Use Characterization  
 
Fluopyram is proposed to be widely used in the US to prevent and/or control certain fungal diseases on many crops including apples, watermelons, selected dry beans, grapes (wine), peanuts, potatoes, cherries, strawberries, sugarbeet, pecans, pistachios, almonds and other tree nuts.  Fluopyram is formulated as a suspension concentrate (SC) alone and mixed with four other fungicides: tebuconazole, trifloxystrobin, pyrimethanil, and prothioconazole.  Formulations are proposed to be applied by ground, airblast, and aerial into foliage (leaves, stems, and shoots), flowers and fruits in addition to application through drip irrigation.

 Table III-1 contains a summary of all crops proposed to be treated with fluopyram and/or its mixtures.
 
Table III-1 Crops included in the proposed crop group use patterns for fluopyram its four premixed formulation
Crop Or Crop Group
Crops In the Group
Almonds
Almonds
Apples
Apples
Cherry
Sweet and Tart Cherries
Watermelon
Watermelon
Beans (Selected / Dry, except Soybeans)
Bean (Lupinus spp., includes grain lupin, sweet lupin, white lupin, and white sweet lupin), Bean (Phaseolus spp., includes field bean, kidney bean, lima bean, navy bean, pinto bean, tepary bean), Bean (Vigna spp., includes adzuki bean, black-eyed pea, catjang, Crowder pea, moth bean, mung bean, rice bean, southern pea, urd bean), Broad Bean (dry), Chickpea, Guar, Lablab Bean, Lentil
Grapes (Wine)
Wine grape varieties only such as but not limited to these varieties: Chardonnay, abernet sauvignon, Syrah, Merlot, Pinot Noir, and Zinfandel
Peanuts
Peanuts
Pecans
Pecans
Pistachios
Pistachios
Potatoes
Potatoes
Strawberries
Strawberries
Sugerbeet
Sugerbeet
Tree Nuts
Almonds, Pecan, Pistachio, Beech nut, Brazil nut, Butternut, Cashew, Chestnut, Chinquapin, Filbert (hazelnut), Hickory nut, Macadamia nut (bush nut), Walnut [including black and English (Persian) walnuts].

 Application information for the use patterns is included in Table III-2.
 
Table III-2 Proposed use patterns for fluopyram and its four premixed formulation including labeled application parameters
Crop
Formulation [1]
                               Maximum Rate per 
                                 Application 
                                 (kg a.i. /ha)
                                Maximum Number 
                              of Applications [2]
                               Maximum Seasonal 
                               Rate (kg a.i./ha)
                      Minimum Application Interval (days)
Application Method
Almond
FLU SOLO
                                     0.249
                                       2
                                     0.499
                                       7
Ground, Air

FLU+PYM
                                     0.246
                                       2
                                     0.498
                                       7

FLU+TFS
                                     0.140
                                      3+
                                     0.498
                                       7

FLU+TEB
                                     0.249
                                       2
                                     0.497
                                       7

Apple
FLU SOLO
                                     0.249
                                       2
                                     0.499
                                       7
Ground

FLU+PYM
                                     0.146
                                      3+
                                     0.498
                                       7

FLU+TFS
                                     0.107
                                      3+
                                     0.386
                                       7

FLU+TEB
                                     0.146
                                      3+
                                     0.497
                                       7

Cherry
FLU SOLO
                                     0.103
                                       2
                                     0.206
                                       5
Ground,  Air

FLU+TFS
                                     0.107
                                       2
                                     0.204
                                       7

FLU+TEB
                                     0.103
                                       2
                                     0.206
                                       7

Watermelon
FLU SOLO
                                     0.249
                                       2
                                     0.499
                                       5
Ground, Drip, 
Green House

FLU+TFS
                                     0.140
                                      3+
                                     0.498
                                       7

FLU+TEB
                                     0.249
                                       2
                                     0.497
                                      10

Beans (Selected / Dry)
FLU SOLO
                                     0.150
                                       2
                                     0.300
                                       7
Ground,  Air

FLU+PTZ
                                     0.150
                                       2
                                     0.300
                                       7

Grapes (Wine)
FLU SOLO
                                     0.249
                                       2
                                     0.499
                                      12
Ground

FLU+PYM
                                     0.246
                                       2
                                     0.498
                                      12

FLU+TFS
                                     0.140
                                      3+
                                     0.498
                                      12

FLU+TEB
                                     0.126
                                      3+
                                     0.497
                                      14

Peanuts
FLU SOLO
                                     0.249
                                       2
                                     0.499
                                      14
Ground,  Air

FLU+PTZ
                                     0.178
                                      2+
                                     0.500
                                      14

FLU+TFS
                                     0.129
                                      3+
                                     0.498
                                      14

FLU+TEB
                                     0.230
                                      2+
                                     0.497
                                      14

Pecan
FLU SOLO
                                     0.249
                                       2
                                     0.499
                                       7
Ground, Air

FLU+TFS
                                     0.140
                                      3+
                                     0.498
                                      14

FLU+TEB
                                     0.249
                                       2
                                     0.497
                                      14

 Pistachios
FLU SOLO
                                     0.249
                                       2
                                     0.499
                                       7
Ground, Air

FLU+PYM
                                     0.246
                                       2
                                     0.498
                                       7

FLU+TFS
                                     0.140
                                       3
                                     0.423
                                      14

FLU+TEB
                                     0.249
                                       2
                                     0.497
                                      10

Potatoes
FLU SOLO
                                     0.103
                                       3
                                     0.309
                                       5
Air

FLU+PYM
                                     0.102
                                       3
                                     0.306
                                       7

FLU+TFS
                                     0.103
                                       3
                                     0.309
                                      14

FLU SOLO
                                     0.199
                                       2
                                     0.399
                                       5
Ground

FLU+PYM
                                     0.102
                                      3+
                                     0.399
                                       7

FLU+TFS
                                     0.107
                                      3+
                                     0.399
                                      14

Strawberries
FLU SOLO
                                     0.249
                                       2
                                     0.499
                                       5
Drip, Greenhouse
Sugerbeet
FLU SOLO
                                     0.125
                                       2
                                     0.250
                                       5
Ground

FLU+TFS
                                     0.125
                                       2
                                     0.250
                                      10

FLU+PTZ
                                     0.111
                                      2+
                                     0.250
                                      14

Tree Nuts
FLU SOLO
                                     0.249
                                       2
                                     0.499
                                       7
Ground, Air

FLU+TFS
                                     0.140
                                       2
                                     0.281
                                       7

FLU+TEB
                                     0.249
                                       2
                                     0.497
                                       7

[1]Premixed Formulations: Fluopyram alone= FLU SOLO; With Tebuconazole= FLU+TEB; With Trifloxystrobin= FLU+TFS; With Pyrimethanil= FLU+PYM; and With Prothioconazole= FLU+PTZ.
[2]Number of applications: 2+ Or 3+ means 2 Or 3 equal applications with one lower application to arrive at the maximum seasonal rate; for example, the Almond rate for  FLU+TFS is three application of 0.140 kg/ha each + 0.078 kg/ha [0.498- (0.140x 3)]=0.078
 
 B.  Exposure Characterization  
 
 	1.  Environmental Fate and Transport Characterization  
 
Physical and chemical properties

The physical and chemical properties of fluopyram are summarized in Table 5.  The chemical is characterized by a water solubility of 16 ppm in acidic and alkaline conditions.  The chemical has a low potential for volatilization from dry and wet surfaces (vapor pressure= 2.33 x 10[-8] torr and Henry's Law constant= 2.94 x 10[-10] atm m[3] mole[-1], respectively at 25 °C). Therefore relatively low partitioning to the air is expected and the small amounts that may partition into the air. 

 Table 5 Physical and chemical properties of fluopyram
 Property
 Description or Value
 Reference
 CAS Name
 Fluopyram (N-[2-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]ethyl]-2(trifluoromethyl)benzamide
 Registrant Data
 
 
 
 Molecular Formula
 C16 H11 Cl F6 N2 O
 
 CAS number
 658066-35-4
 
 PC code
 080302
 
 Molecular Weight
 (g/mol)
 396.72 
 
 Solubility 
 (@ 20 ̊C)
 
 
 
 
 
pH 4                --> 15 mg/L
pH 6.7 & 7.0   --> 16 mg/L
 pH 9                --> 15 mg/L 
 In neutral/near neutral de-ionized water (pH 6.7): 16 ppm;
 In aqueous buffers: 15 ppm @ pH 4; 16 ppm  @ pH 7; and 15 ppm @ pH 9
In heptane	             0.66 x 10 [3] ppm
In toluene	           62.20 x 10 [3] ppm
In dichloromethane, methanol, acetone, ethyl acetate, 
and di-methyl sulfoxide          > 250 x 10 [3] ppm
 
 Water
 MRID 47372247
 
 Solvents
 MRID 4732248
 
 
 Vapor pressure
20°C --> 9.00 x 10[-9] torr;   1.2 x 10[-6] Pa;    1.18 x 10[-11]atm
25°C --> 2.33 x 10[-8] torr;    3.1 x 10[-6] Pa;    3.06 x 10[-11]atm
50°C --> 2.18 x 10[-6] torr;   2.9 x 10[-4] Pa;    2.86 x 10-9 atm
 MRID 47372249
 Henry's Law Constant (@ pH 7 & 20 ̊C)
 2.94 x 10[-10] atm m[3] mole[-1]
 Calculated from VP at 25°C
 Kow 
 2,060 (Log Kow = 3.314)
 MRID 47372245
 
 The n-octanol water partition coefficient (Kow) of fluopyram (2,060) suggests a moderate potential for bioaccumulation in aquatic organisms such as fish. 

Fate and Transport Properties

The fate and transport behaviour of fluopyram has been investigated in a series of laboratory and field studies. The laboratory studies were all conducted with 14C-labelled active substance uniformly labelled in one of the two rings: the phenyl and the pyridyl rings (Figure 3).

                                       
                                       
    * denotes position of radiolabel, uniformly labelled in the phenyl ring
                                       
                                       
* denotes position of radiolabel, labelled in the 2- and 6-position of the pyridyl ring
                                       
                           [phenyl-UL-14C] Fluopyram
                          [pyridyl-2,6-14C] Fluopyram
 Figure 3 Positions of radiolabels for fluopyram used in fate and transport studies
 		
 
 a. Abiotic Degradation  
 
 Fluopyram labeled at both the [phenyl-UL-[14]C] and the [pyrrdyl-2,6 [14]C] was used in conducting hydrolysis and photolysis studies.  In the hydrolysis study, the chemical was shown to be practically stable in acidic/neutral/alkaline aqueous buffered solutions (pHs 4, 7 and 9; MRIDs 473723-03/04).  The chemical was also shown to degrade relatively slowly by aqueous photolysis (t(1/2)= 57 days; MRID 473723-07) and was practically stable by photolysis on soil surfaces subjected to sunlight (t(1/2)= 54 days, MRID 473723-06).  Results indicate that hydrolysis and aqueous and on soil photolysis are not important in fluopyram dissipation in the natural environment. The fate properties of fluopyram in abiotic systems are summarized in Table 6. 
 
 Table 6 Fate properties of fluopyram in abiotic systems
 Property
 Description or Value
 Reference*
 Hydrolysis half-life
 Stable
 473723-03
 Aqueous photolysis 
 half-lives (two labels) 
 
 57 days  (mean value) in aqueous buffered solution at pH 7 **
 87 days  (mean value) in sterile natural water from the Rhine River
 473723-04
 And
 473723-05
 Soil photolysis half-life
 Stable
 473723-06
 * Reference numbers are the studies MRID numbers
** No degradation was observed in dark controls and only phenyl labeled 13-d sample was analyzed, which indicated 96.7% of the applied amount; therefore, no rate constant for the dark controls could be calculated.  
 
 b. Biotic Degradation 
 
The biotic fate properties of fluopyram in biotic systems are summarized in Table 7.
 
 Table 7 Fate and transport properties of fluopyram in biotic systems
 Property
 Description or Value
 Reference*
 Aerobic soil metabolism 
 half-lives (1[st] value for Pyridyl label and the 2[nd] value for Phenyl label)
 
 
 
210 & 221 days Hoefchen am Hohenseh soil, Germany (silt loam, pH 6.7, OC 2.4%)
464 & 231 days Laacherhof AXXa soil, Germany (sandy loam, pH 6.2, OC 2.2%)
250 & 339 days Laacherhof Wurmwiese soil, Germany (sandy loam, pH 5.2, OC 1.8%)
162 & 165 days Dollendorf soil, Germany (clay loam, pH 7.3, OC 5.1%)
561 & 746 days Porterville soil, CA (sandy loam, pH 7.9, OC 0.5%)
583 & 654 days Springfield soil, NE (silty clay loam, pH 6.5, OC 1.7%)
 Major Degradation products: None
Minor Degradation products: Fluopyram-7-hydroxy (7-Hydroxy: max. 4.2%); Fluopyram-pyridyl-carboxylic acid (PCA: max. 0.7%); Fluopyram-methyl-sulfoxide (Methyl Sulfoxide: max. 1.0%) and Fluopyram-benzamide (Benzamide: 1.1%)
 473723-07
 473723-08
 and 
 473723-09
 
 
 
 Anaerobic soil half-lives
 Stable for two labels
 Major & Minor Degradation products: None	
 473723-10
 Aerobic aquatic
 Half-lives (two labels, two systems)
 Pond water/sediment system from Lawrence , Kansas: Water (pH 7.7 and dissolved OC 15.6 ppm) and sediment: (Clay loam, OC 3.7%, pH 5.3):
 1,000  days (Phenyl label) & 648 days ([Pyridyl label) in the total system (extrapolated beyond the study duration of 120 days) 
 (Note: the chemical dissipated from the water into the sediment with a half-life of 17 & 14 days, respectively)
 Pond water/sediment system from Germany: Water (pH 6.8) and sediment: (sand, OC 1.1%, pH 5.7):
 1,190 days (Phenyl label) & 1,470  days ([Pyridyl label) in the total system (extrapolated beyond the study duration of 120 days), 
 Major & Minor Degradation products: practically None
 473723-11
 Anaerobic aquatic 
 half-lives (two Labels/one system)
 
 Pond water/sediment system from Lawrence , Kansas: Water (pH 7.7 and dissolved OC 15.6 ppm) and sediment: (Clay loam, OC 3.7%, pH 5.3):
 1,580 days (Phenyl label) & 1,410 days ([Pyridyl label) in the total system (extrapolated beyond the study duration of 121 days, 
 Major & Minor Degradation products: practically None
 473723-12
 and
 473723-13
 
 Terrestrial field dissipation
 half-lives (US soils)
 
 
 
 
 
   24 days (GA bare-ground Loamy sand soil);
   83 days (ND bare-ground loam soil);
 163 days (WA bare-ground sandy loam soil);
 174 days (CA bare-ground sandy loam soil); and      
 539 days (NY bare-ground loamy sand soil)
 
 Major Degradation products: Two major transformation products, Fluopyram-benzamide and Fluopyram-PCA with maximum concentrations of 9.8 ug/kg (equivalent to 19% of 0-day parent) and 10.2  ug/kg (16%), respectively, at 6 DAT
 Minor Degradation products: one minor transformation product, Fluopyram-7-hydroxy with a maximum concentration of 3.0 ug/kg (3% of 0-day parent equivalent) were observed at the CA site
 475670-01
 475670-02
 475670-03
 475670-04
 and
 475670-05
 
 Fish 
 Bio-concentration
 (BCF= Bio concentration Factor)
 
 
 
 Bluegill sunfish at low dose (6 ppb) and 42-day exposure/14-day depuration: Max. BCFs= 49 (edible) and 169 (non-edible)
 Max. Observed at 28 days of exposure (reached steady state)
 59% and 81% depurated after 14 days from edible and non-edible tissues, respectively
 
 Bluegill sunfish at high dose (60 ppb) and 42-day exposure/14-day depuration:  Max. BCFs= 42 (edible) and 147 (non-edible)
 Max. Observed at 28 days of exposure (reached steady state)
 72% and 85% depurated after 14 days from edible and non-edible tissues, respectively
 
 Transformation products: 
 In water: parent accounted for >97% with 1% of the total radioactive residue was Fluopyram-7-hydroxy in water samples collected late during the exposure period.
 In Fish tissue: parent accounted for 25-55% in the edible tissue and 11.0-21.9% in the non-edible tissue. Transformation products were identified in edible and non-edible tissues and included 18-7% of Fluopyram-7-hydroxy @ 7 and 14-day exposure. Other minor degradates included Fluopyram-7-OH-GA (isomer 1), Fluopyram-8-OH-GA (isomer 2) and Fluopyram-pyridyl acetic acid 
 473723-37
 
 
 * Reference numbers are the studies MRID numbers

Fate data presented in Table 7 are a summary of the results obtained from studies including: laboratory degradation studies in aerobic/anaerobic soil and water/sediment systems, field dissipation in terrestrial systems, and fish bio-concentration. A summary of these studies is included in Appendix A.
 
 c. Tranformation Profile  
 
The primary metabolic pathway for fluopyram in soil is hydroxylation in the 7-position of the molecule to form the hydroxylated metabolite, Fluopyram-7-hydroxy.  Fluopyram-7-hydroxy has been identified in all soils tested in the laboratory and in the field in concentrations ranging from 3 to <5% throughout the study periods of nearly one year.  The maintained nearly constant low concentration of this degradate suggests that it is a transient species.  It appears that the transient Fluopyram-7-hydroxy is cleaved to form, in most cases, minor quantities of the metabolites Fluopyram-PCA (pyridyl-carboxylic acid) and Fluopyram benzamide. Further degradation of the pyridyl- Fluopyram-PCA appear to result in the formation of the degradate methyl-sulfoxide.  In addition the expected very limited aquatic photo-degradation of fluopyram results in the degradate lactam in quantities ranging from 1 to 13% (Figure 4).

Figure 4 Environmental degradation pathways for fluopyram 

                                                   Fluopyram Parent
Limited aerobic soil degradation (Parent hydroxylation)
                        Very limited aqueous photolysis

                           Molecular Cleavage

                                    

                                    Lactam
                                                     7-Hydroxy

        Cleavage

 

                                   Benzamide
                                      PCA

                               Methyl Sulfoxide
Chemical Names (Molecular Formula  -  Weight; No CAS number reported)
Lactam: 2,9-bis(trifluoromethyl)-6,7-dihydropyrido[2,3-e][2]benza-zocin-8(5H)-one [C16H10F6N2O - 360.26 g mol-1]
7-Hydroxy: N-{2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-2-hydroxyethyl}-2-(trifluoromethyl)benzamide [C16H11Cl F6N2O2 - 412.72 g mol-1]
Benzamide: 2-(trifluoromethyl)benzamide [C8H6F3NO -189.14 g mol-1]
PCA: 3-chloro-5-(trifluoromethyl)pyridine-2-carboxylic acid [C7H3Cl F3NO2 - 225.26 g mol-1]
Methyl Sulfoxide: 3-(methylsulfinyl)-5-(trifluoromethyl)pyridine-2-carboxylic acid [C8H6F3NO3S - 253.20 g mol-1 ]
 
 d. Mobility 		
 
The adsorption/desorption characteristics of fluopyram were determined for five soils in a concentration range of two orders of magnitude 0.01 and 1 mg a.i./L (MRID 473723-01) . The percent adsorption of applied amount were 48-76%, 71-83%, 58-74%, 44-62% and 55 to 74% in sandy loam, silt loam, loam, loamy sand and clay loam soils, respectively.  For this adsorption phase, the range of adsorption values was 3.16 to 8.37 L/Kg for Kd, 266 to 460 L/Kg for Koc, and 316 to 591 for Kfoc.  For Freundlich isotherm, 1/n values were below 1.0 for all soils (0.763 to 0.863) indicating that the concentration of the test item affected the adsorption behavior.  Based on Kfoc values, mobility of fluopyram in the tested soils is classified as moderate in accordance to the FAO mobility classification.  Additionally, the adsorption/desorption behavior of the degradate [pyridine-2,6-14C] Fluopyram-7-hydroxy was studied in four German soils: sandy loam, silt loam, sandy loam, and loam soils (MRID 473723-02).  The percent of applied amount adsorbed in sandy loam, silt loam, sandy loam, and loam soils were 40-49, 56-66, 40-48 and 34-44, respectively.  The adsorption Kd values for sandy loam, silt loam, sandy loam, and loam soils were 1.36, 2.54, 1.38 and 1.03 L/Kg, respectively.  The corresponding Koc values were 91, 159, 86 and 94 L/Kg and Kfoc values were 209, 327, 220, and 277 L/Kg.    Based on Kfoc values, the mobility of the 7-hydroxy degradate of fluopyram in the tested soils is classified as high to moderate in accordance to the FAO mobility classification.

For the parent desorption phase, the amounts of desorbed material desorbed were 15-59%, 12-49%, 17-58%, 25-67% and 18 to 61% in sandy loam, silt loam, loam, loamy sand and clay loam soils, respectively.  For this desorption phase, the range of desorption values was 6.32 to 13.15 L/Kg for Kd and 444 to 834 L/Kg for Koc.  Furthermore, the amount of degradate Fluopyram-7-hydroxy desorbed from the adsorbed material ranged from 18 to 38%.  The desorption Kd for sandy loam, silt loam, sandy loam, and loam soils were 3.78, 7.16, 3.88 and 3.54 L/Kg and the Koc values were 252, 447, 243 and 322.  For both parent and 7-hydroxy degradate, desorption Koc values were higher than the adsorption Koc values, indicating a strengthened binding of the test material once adsorbed to the soil. Adsorption coefficients for tested soils are summarized in Table 8.

 Table 8 Transport properties of fluopyram and degradate
 Property
 Description or Value
 Reference*
 I. Fluopyram parent
 Adsorption coefficient
 
 
 
Kfoc= 397 L kg [-1] (Laacherhof AXXa soil, Germany, sandy loam, pH 6.0, OC 1.3%);
Kfoc= 388 L kg [-1] (Hoefchen am Hohenseh soil, Germany, silt loam, pH 6.1, OC 2.6%);
Kfoc= 316 L kg [-1] (Laacherhof Wurmwiese soil, Germany, Loam, pH 5.4, OC 2.1%);
Kfoc= 501 L kg [-1] (Pikeville soil, North Carolina, Loamy sand, pH 5.0, OC 1.1%); and
 Kfoc= 591 L kg [-1] (Stilwell soil, Kansas, clay loam, pH 5.4, OC 1.1%)
 473723-01
 
 
 II. Fluopyram 7-hydroxy degradate
 Adsorption coefficient

pyridine-2,6-[14]C] Fluopyram-7-hydroxy 

Kfoc= 290 L kg [-1] (Laacherhof AIIIa soil, Germany, sandy loam, pH 6.4, OC 1.1%);
Kfoc= 277 L kg [-1] (Laacherhof  AXXa soil, Germany, sandy loam, pH 6.1, OC 1.5%);
Kfoc= 327 L kg [-1] (Hoefchen am Hohenseh soil, Germany, silt loam, pH 6.6, OC 1.6%); and
 Kfoc= 220 L kg [-1] (Laacherhof, Wurmwiese soil, Germany (sandy loam, pH 5.1, OC 1.6%)
 473723-02
 
 * Reference numbers are the studies MRID numbers.
 
 	2.  Measures of Aquatic Exposure 	 
 Fluopyram has a low vapor pressure (9x10[-9] torr) and its solubility in water is 16 ppm.  Fluopyram is highly persistence under all other abiotic/biotic conditions tested in the laboratory.  The chemical is stable to aqueous hydrolysis in neutral and alkaline conditions, photolysis on soil, anaerobic soil metabolism, aerobic and anaerobic aquatic metabolism in sediment/water systems.  Aqueous photolysis half-lives ranged from 87 days in natural water system to 57 days in laboratory pH 7 buffered systems.  In field studies, fluopyram has shown similar persistence especially in two out of five terrestrial field dissipation studies on bare-ground plots (half-lives ranged from 24 to 83 days in two studies in GA and ND and 163 to 539 days in three studies in WA, CA, and NY).  For mobility, fluopyram appears to have medium affinity to soil and sediment particles rendering it to be moderately mobile in systems with varied textures and organic matter content (Kfoc ranges from 316 to 591 L/Kg).  The major routes of dissipation for fluopyram in important compartments of the natural environment appear to be the slight bio-transformation in aerobic systems.  The relative high persistent, and mobility of fluopyram suggests that the chemical may cause contamination to ground water.  However, estimated EEC for ground water was one order of magnitude lower than surface water EECs. Fluopyram can also reach surface water through erosion, drift and/or run-off events.
 
Based on fate and transport properties and the degradation profile of fluopyram, environmental exposure of aquatic systems may occur from parent and two main degradates, namely: methyl sulfoxide and benzamide in addition to limited quantities of lactam in shallow clear water systems.  Examination of the soil metabolism data suggests that a limited quantity of these degradates is expected to be released to the environment.  Therefore, parent exposure is expected to represent environmental exposure based on the limited amount of degradates formed and their expected equal or lower toxicity. Only one study was submitted for degradate toxicity which suggest parent is more toxic than degradate. In this respect, the Global Residues of Concern Knowledgebase Subcommittee (Global ROCKS) decided that only parent is the residue of concern in drinking water exposure. The decision was based on the degradation profile of the parent which shows a very low level of degradation in important environmental compartments. 
 
 a. Application Methods  
 
Fluopyram is formulated as suspension concentrates alone or admixed with other fungicides and applied as liquid sprays or through drip irrigation (watermelons and strawberries). Application equipment includes various types of ground, airblast, and aerial sprayers.  Ground application is permitted for all crops while aerial application is limited to specific crops sometimes with lower application rates. Exposure was evaluated for all crops and all application methods.
 
 b. Label Application Rates and Intervals  
 
Fluopyram labels may be categorized into two types: labels for manufacturing uses (including technical grade fluopyram) and its formulated products or end-use products.  While technical products, which contain fluopyram of high purity, are not used directly in the environment, they are used to make formulated products, which can be applied in specific areas to control fungal diseases.  The formulated product labels legally limit fluopyram potential use to only those sites that are specified on the labels.  Uses being assessed are summarized in Table 9 along with representative scenarios and the chosen first application dates.

Table 9 Rates (maximums) and application intervals (minimums) representing labeled uses for fluopyram and its four mixtures
Crop
Scenario*
                            Single Application Rate
                            Number of Applications
                                Date of 1[st] 
                             Application (DD/MM)**

                                   lb a.i./A
                                  Kg a.i./ha
                                       
                                       
(1) Aerial Application (95% efficiency, 5% drift)
Beans (dry)
MIbeansSTD
                                     0.134
                                     0.150
                                       2
                                     01-08

WAbeansNMC
                                     0.134
                                     0.150
                                       2
                                     15-08

ILbeansNMC
                                     0.134
                                     0.150
                                       2
                                     15-08
Cherries Only
MICherriesSTD
                                     0.092
                                     0.103
                                       2
                                     10-07

CAfruit_WirrigSTD
                                     0.092
                                     0.103
                                       2
                                     30-04
Peanuts
NCpeanutSTD
                                     0.222
                                     0.249
                                       2
                                     15-07
Potatoes
CAPotatoRLF_V2
                                     0.092
                                     0.103
                                       3
                                     01-06

FLpotatoNMC
                                     0.092
                                     0.103
                                       3
                                     15-03

IDNpotato_WirrigSTD
                                     0.092
                                     0.103
                                       3
                                     20-06

WApotatoNMC
                                     0.092
                                     0.103
                                       3
                                     20-06

MEpotatoSTD
                                     0.092
                                     0.103
                                       3
                                     01-07
Tree Nuts
CAalmond_WirrigSTD
                                     0.222
                                     0.249
                                       2
                                     20-02

GAPecansSTD
                                     0.222
                                     0.249
                                       2
                                     01-08

ORfilbertsSTD
                                     0.222
                                     0.249
                                       2
                                     20-03

WAorchardsNMC
                                     0.222
                                     0.249
                                       2
                                     15-04
(2) Ground Application (99% efficiency; Airblast 3% drift/CAM=2, Ground 1% drift/CAM=2, and/or drip 0% drift/CAM=1)
Apples
NCappleSTD
                                     0.222
                                     0.249
                                       2
                                     15-05

ORappleSTD
                                     0.222
                                     0.249
                                       2
                                     15-05

WA orchards 1
                                     0.222
                                     0.249
                                       2
                                     15-04

PAappleSTD_V2
                                     0.222
                                     0.249
                                       2
                                     15-05

CAfruit_WirrigSTD
                                     0.222
                                     0.249
                                       2
                                     15-04
Beans (dry)
MIbeansSTD
                                     0.134
                                     0.15
                                       2
                                     01-08

WAbeansNMC
                                     0.134
                                     0.15
                                       2
                                     15-08

ILbeansNMC
                                     0.134
                                     0.15
                                       2
                                     15-08
Cherries Only
MICherriesSTD
                                     0.092
                                     0.103
                                       2
                                     10-07

CAfruit_WirrigSTD
                                     0.092
                                     0.103
                                       2
                                     30-04
Watermelon
CAMelonsRLF_V2
                                     0.222
                                     0.249
                                       2
                                     20-06

FLcucumberSTD
                                     0.222
                                     0.249
                                       2
                                     20-11

MImelonStd
                                     0.222
                                     0.249
                                       2
                                     01-07

MOmelonStd
                                     0.222
                                     0.249
                                       2
                                     25-06

NJmelonStd
                                     0.222
                                     0.249
                                       2
                                     01-07

STXmelonNMC
                                     0.222
                                     0.249
                                       2
                                     20-06
Watermelon, Drip
CAMelonsRLF_V2
                                     0.222
                                     0.249
                                       2
                                     20-06

FLcucumberSTD
                                     0.222
                                     0.249
                                       2
                                     20-11

MImelonStd
                                     0.222
                                     0.249
                                       2
                                     01-07

MOmelonStd
                                     0.222
                                     0.249
                                       2
                                     25-06

NJmelonStd
                                     0.222
                                     0.249
                                       2
                                     01-07

STXmelonNMC
                                     0.222
                                     0.249
                                       2
                                     20-06
Grapes (Wine
CAWineGrapesRLF_V2
                                     0.222
                                     0.249
                                       2
                                     01-04

NYGrapesSTD
                                     0.222
                                     0.249
                                       2
                                     15-04
Peanuts
NCpeanutSTD
                                     0.222
                                     0.249
                                       2
                                     15-07
Potatoes
CAPotatoRLF_V2
                                     0.178
                                     0.199
                                       2
                                     01-06

FLpotatoNMC
                                     0.178
                                     0.199
                                       2
                                     15-03

IDNpotato_WirrigSTD
                                     0.178
                                     0.199
                                       2
                                     20-06

WApotatoNMC
                                     0.178
                                     0.199
                                       2
                                     20-06

MEpotatoSTD
                                     0.178
                                     0.199
                                       2
                                     01-07
Strawberries, Drip only
FLstrawberry_WirrigSTD
                                     0.222
                                     0.249
                                       2
                                     01-12

CAStrawberry-noplasticRLF_V2
                                     0.222
                                     0.249
                                       2
                                     15-06
Sugerbeet
MNsugarbeetSTD
                                     0.112
                                     0.125
                                       2
                                     01-05

CAsugarbeet_WirrigOP
                                     0.112
                                     0.125
                                       2
                                     01-04
Tree Nuts
CAalmond_WirrigSTD
                                     0.222
                                     0.249
                                       2
                                     20-02

GAPecansSTD
                                     0.222
                                     0.249
                                       2
                                     01-08

ORfilbertsSTD
                                     0.222
                                     0.249
                                       2
                                     20-03

WAorchardsNMC
                                     0.222
                                     0.249
                                       2
                                     15-04
* NMC= N-methyl carbamate cumulative scenario; RLF= Red Legged Frog scenario; and OP= organophosphate pesticides: These scenarios were used for the risk assessments stated and may represent high vulnerable use sites for this assessment.
** 1[st] application dates were selected based on information in the label, pest and stage of crop growth that may be associated with the first application date.

 c. Modeling Approach  
 
Aquatic exposures are quantitatively estimated for all of assessed uses using scenarios that represent high exposure sites for fluopyram 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.  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 they tend to persist for only short periods of time and are then carried downstream. 
 
 d. Model Inputs  
 
Environmental fate and transport and other data used as parameters for the three PRZM/EXAMS runs are listed in Table 10.  

Table 10 Summary of PRZM/EXAMS environmental fate and transport data used as aquatic exposure inputs
Input Parameter [1] (Unit)
                                    Value*
Molecular Weight g/mole
                                    396.72
Henry's constant (atm-m3 mol-1 @ 20 [o]C)
                                   2.94E-10
Solubility in Water(mg/L)
                                      16
Photolysis in Water (t(1/2) in days @ pH 7)
                                      57
Aerobic Soil Metabolism (90[th] % t(1/2) in days for 6 soils x two labels)
                                      464
Hydrolysis (t(1/2) in days @ pH 7)
                                    Stable
Aerobic Aquatic Metabolism (90[th] % t(1/2) in days whole system t(1/2) in days for two systems x two labels)
                                     1,360
Anaerobic Aquatic Metabolism (90[th] % t(1/2) in days whole system t(1/2) in days for one system x two labels)
                                     1,757
Koc (Average of five values in L/Kg)
                                      439
Application rate and frequency
                 Depends on the crop (refer to Table 2, above)
Application intervals 

Chemical Application Method (CAM)
                                       2
Application Efficiency
                            95% Aerial; 99% Ground
Spray Drift Fraction
                         0.05 Aerial; 0.03 Airblast, 
                                and 0.01 Ground
 
 e. Aquatic EECs  
 
Aquatic exposure EECs for the various crop use patterns are summarized in Table 11.  Peak concentrations varied from 0.01 to 5.47 ug a.i./L.

Table 11 Surface water 1-in-10 Year EECs (μg/L) for fluopyram use patterns applied by aerial and ground equipment 
Crop
Scenario
                                     Peak
                                    21-day
                                    60-day
Aerial
Beans (dry)
MIbeansSTD
                                     1.56
                                     0.228
                                     0.104

WAbeansNMC
                                     0.47
                                     0.112
                                     0.039

ILbeansNMC
                                     1.31
                                     0.225
                                     0.122
Cherries Only
MICherriesSTD
                                     0.59
                                     0.105
                                     0.047

CAfruit_WirrigSTD
                                     0.29
                                     0.059
                                     0.021
Peanuts
NCpeanutSTD
                                     2.29
                                     0.304
                                     0.119
Potatoes
CAPotatoRLF_V2
                                     0.37
                                     0.072
                                     0.025

FLpotatoNMC
                                     3.22
                                     0.430
                                     0.172

IDNpotato_WirrigSTD
                                     0.22
                                     0.074
                                     0.032

WApotatoNMC
                                     1.26
                                     0.188
                                     0.071

MEpotatoSTD
                                     1.29
                                     0.322
                                     0.140
Tree Nuts
CAalmond_WirrigSTD
                                     0.98
                                     0.344
                                     0.130

GAPecansSTD
                                     3.71
                                     0.402
                                     0.148

ORfilbertsSTD
                                     2.79
                                     0.407
                                     0.168

WAorchardsNMC
                                     0.73
                                     0.247
                                     0.087
Ground
Apples
NCappleSTD
                                     4.00
                                     0.671
                                     0.240

ORappleSTD
                                     0.43
                                     0.139
                                     0.062

WA orchards 1
                                     0.55
                                     0.154
                                     0.054

PAappleSTD_V2
                                     2.59
                                     0.465
                                     0.167

CAfruit_WirrigSTD
                                     0.55
                                     0.152
                                     0.053
Beans (dry)
MIbeansSTD
                                     1.63
                                     0.190
                                     0.104

WAbeansNMC
                                     0.40
                                     0.054
                                     0.019

ILbeansNMC
                                     1.36
                                     0.227
                                     0.125
Cherries Only
MICherriesSTD
                                     0.62
                                     0.095
                                     0.041

CAfruit_WirrigSTD
                                     0.17
                                     0.036
                                     0.013
Watermelon
CAMelonsRLF_V2
                                     0.01
                                     0.002
                                     0.001

FLcucumberSTD
                                     4.63
                                     0.491
                                     0.204

MImelonStd
                                     1.14
                                     0.160
                                     0.062

MOmelonStd
                                     2.34
                                     0.315
                                     0.112

NJmelonStd
                                     2.00
                                     0.179
                                     0.071

STXmelonNMC
                                     7.31
                                     0.652
                                     0.257
Watermelon, Drip
CAMelonsRLF_V2
                                     0.01
                                     0.002
                                     0.001

FLcucumberSTD
                                     5.47
                                     0.712
                                     0.286

MImelonStd
                                     4.37
                                     0.381
                                     0.145

MOmelonStd
                                     3.86
                                     0.347
                                     0.123

NJmelonStd
                                     4.77
                                     0.376
                                     0.142

STXmelonNMC
                                     7.31
                                     0.639
                                     0.257
Grapes (Wine)
CAWineGrapesRLF_V2
                                     0.37
                                     0.073
                                     0.030

NYGrapesSTD
                                     2.25
                                     0.526
                                     0.207
Peanuts
NCpeanutSTD
                                     2.32
                                     0.245
                                     0.096
Potatoes
CAPotatoRLF_V2
                                     0.33
                                     0.035
                                     0.012

FLpotatoNMC
                                     4.39
                                     0.476
                                     0.217

IDNpotato_WirrigSTD
                                     0.32
                                     0.095
                                     0.040

WApotatoNMC
                                     1.70
                                     0.250
                                     0.088

MEpotatoSTD
                                     1.68
                                     0.380
                                     0.150
Strawberries, Drip only
FLstrawberry_WirrigSTD
                                     3.77
                                     0.668
                                     0.236

CAStrawberry-noplasticRLF_V2
                                     1.08
                                     0.164
                                     0.062
Sugerbeet
MNsugarbeetSTD
                                     0.98
                                     0.202
                                     0.076

CAsugarbeet_WirrigOP
                                     0.23
                                     0.042
                                     0.016
Tree Nuts
CAalmond_WirrigSTD
                                     0.81
                                     0.261
                                     0.101

GAPecansSTD
                                     3.61
                                     0.382
                                     0.142

ORfilbertsSTD
                                     2.90
                                     0.392
                                     0.157

WAorchardsNMC
                                     0.55
                                     0.154
                                     0.054

Estimation of Sediment Concentrations

Exposure to sediment and pore water in aquatic systems was also obtained for selected runs including scenarios with the highest and lowest surface water EECs. These data are summarized in Table 12.

Table 12 Sediment (μg/Kg) and pore water EECs (μg/L) for fluopyram use patterns applied by aerial and ground application methods
Crop
Scenario
Pore Water EECs (ppb)
Sediment EECs (ppb) 

Peak
21-day
60 day
Peak
21-day
60 day
                                    Ground
Tree Nuts
GA pecans
                                     0.05
                                     0.01
                                     0.004
                                     0.898
                                     0.184
                                     0.067
Potatoes
FL potato
                                     0.09
                                     0.027
                                     0.01
                                     1.619
                                     0.487
                                     0.183
Potatoes
IDN potato
                                     0.004
                                     0.002
                                     0.001
                                     0.072
                                     0.039
                                     0.017
Cherries Only
CA fruits 2
                                     0.004
                                     0.002
                                     0.001
                                     0.079
                                     0.034
                                     0.012
                                    Aerial
Watermelon, Ground
STX melon
                                     0.142
                                     0.02
                                     0.007
                                     2.55
                                     0.362
                                     0.127
Watermelon, Drip
FL cucumber 
                                     0.069
                                     0.02
                                     0.009
                                     1.246
                                     0.355
                                     0.16
Watermelon, Drip
CA Melons
                                       0
                                       0
                                       0
                                     0.009
                                     0.008
                                     0.005

 g. Aquatic Exposure Monitoring (Field Data) 
 
 This is a new pesticide and therefore no data were identified to provide information on aquatic monitoring.
 
 	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 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 residues from a single pesticide in a given exposure scenario. Application methods of fluopyram include ground or aerial spray application and drip irrigation for agricultural uses. For this terrestrial exposure assessment, spray applications are considered as described below. When considering residues on wildlife dietary items, drip irrigation applications are considered to have substantially reduced exposure potential to non-target wildlife compared to foliar spray applications, with the exception of soil-dwelling organisms.
 
 		a. Terrestrial Animal Exposure Modeling- Spray Applications  
 
 One concern with pesticide applications is that birds and mammals may be exposed shortly after application through oral or dietary exposure to vegetative plant material or insects when foraging in the treated fields for nesting material or food.  Therefore, for fluopyram spray applications, estimation of pesticide concentrations in wildlife food items focuses on quantifying possible dietary ingestion of residues on vegetative matter and insects. The Terrestrial Residue EXposure model (T-REX, Version 1.4.1, dated October 8, 2008) is used to estimate exposures and risks to avian and mammalian species.  Input values for avian and mammalian acute and chronic toxicity as well as chemical application and foliar dissipation half-life data are required to run the model. The model provides estimates of exposure concentrations and risk quotients (RQs).  Specifically, the model provides estimates of concentrations (upper-bound and mean) of chemical residues on the surface of different types of foliage and insects that may be dietary sources of exposure to mammalian and avian species (with birds as surrogates for terrestrial-phase amphibians and reptiles). The surface residue concentration (ppm) is estimated by multiplying the application rate (pounds active ingredient per acre) by a value specific to each food item. These values (termed the Hoerger-Kenaga estimates) along with a more detailed discussion of the methodology implemented by T-REX, are presented in Appendix D (T-REX Model).
 
 For multiple applications, the EEC is determined by adding the mass on the surface immediately following the application to the mass of the chemical still present on the surfaces on the day of application (determined based on first order kinetics using the foliar half-life as the rate constant).  Input values used for estimating avian and mammalian exposure risks to fluopyram are summarized in Table 8.  In the absence of available foliar dissipation studies, a default foliar half-life of 35 days is used based on the work of Willis and McDowell (1987). For this screening level assessment, the default foliar half-life of 35 days was used for the terrestrial exposure modeling, with an additional analysis of available submitted foliar dissipation data (see the Description of Assumptions, Limitations, Uncertainties, Strengths and Data Gaps section). In this respect, the EECs for fluopyram may be an overestimation of actual concentrations, if the half-life under field conditions is lower than the default value.  
 
 Risks could also be overestimated if the actual application rate, frequency of application or number of applications is lower than the input parameters used for the conservative exposure scenario that was modeled. For this risk assessment, the T-REX model was run for agricultural uses with the maximum proposed application rate (0.222 lb a.i./A), 2 applications (maximum number of applications), and a 5-day application interval (the minimum application interval), to assess risk to terrestrial organisms (see Table 13). 
 
 However, terrestrial EECs could be an underestimation of actual exposure concentrations in the environment. Although the label stated that fluopyram can be applied via foliar spray application up to 2 times per season for the crops with the highest seasonal application rate (watermelons, and strawberries), for this risk assessment, EFED assumed that fluopyram was applied at a maximum of 2 times per year.  If there are conditions under which there is more than one growing season for a crop within a single year, exposure estimates and risk to terrestrial organisms could be significantly underestimated.  
 
 Table 13.  Input parameters used in T-REX v1.4.1 to determine terrestrial EECs for the maximum fluopyram spray application scenario. a 
                                 Input Variable
                                Parameter Value
                                     Source
 Maximum application rate
                                0.222 lbs a.i./A
                         Fluopyram 500 SC Product Label
 Maximum # of applications per year
                                       2
                         Fluopyram 500 SC Product Label
 Minimum application interval
                                     5 days
         Fluopyram 500 SC Product Label (watermelons and strawberries)
 Foliar half-life
                                    35 days
                              T-REX Default Value 
 [a] Representative of the maximum exposure scenario for all crop uses.
 
 The EECs on food items may be compared directly with dietary toxicity data or converted to an oral dose.  For mammals, the residue concentration is converted to daily oral dose based on the fraction of body weight consumed daily as estimated through mammalian allometric relationships. The screening-level risk assessment for fluopyram considers upper-bound predicted residues as the measure of exposure. Summaries of the predicted upper-bound and mean residues of fluopyram that may be expected to occur on selected avian or mammalian food items immediately following application for the maximum use scenario are presented in Table 14.  
 
 For the maximum fluopyram spray application scenario, acute concentrations on foliar surfaces ranged from 6.35 to 101.54 ppm for upper-bound residues and 2.96 to 35.96 ppm for mean residues.  
 
 Table 14.  Upper-bound and mean terrestrial dietary EECs estimated for the maximum fluopyram spray application scenario (Kenaga values). [a]
                                  Forage Type
                           Upper-bound Residues (ppm)
                              Mean Residues (ppm)
 short grass
                                     101.54
                                     35.96
 tall grass
                                     46.54
                                     15.23
 broadleaf plants and small insects
                                     57.11
                                     19.04
 fruits/pods/large insects
                                      6.35
                                      2.96
 
 
 		b. Terrestrial Exposure Monitoring (Field Data)  
 
 Fluopyram is a new chemical, therefore no data are available on terrestrial monitoring for fluopyram.
 
 
 	4.  Non-Target Terrestrial Plant Exposure Assessment 
 
 A preliminary run of TERR-PLANT was conducted using the maximum application rate for ground application and aerial applications, 0.222 lbs a.i./acre. The modeled drift fraction varies depending on application method, either 1% for ground applications or 5% for aerial applications. The maximum modeled EECs ranged from 0.002 (spray drift) to 0.047 (semi-aquatic areas) lbs a.i./A for ground application and from 0.011 (spray drift) to 0.055 (semi-aquatic areas) lbs a.i./A for aerial application.
 
 
 C.  Ecological Effects Characterization  
 
 This, effects characterization describes the types of effects fluopyram can produce in aquatic or terrestrial organisms.  As fluopyram is a new pesticide, this characterization is based on registrant-submitted studies that describe acute and chronic effects toxicity information for various aquatic and terrestrial animals and plants.  Appendix E summarizes the results of the registrant-submitted toxicity studies used to characterize effects for this risk assessment.  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 mollusk, and a fish.  Also, neither reptiles nor amphibians are commonly tested.  In the absence of toxicity data for reptiles and terrestrial phase amphibians, this risk assessment assumes that the sensitivity of birds, terrestrial-phase amphibians, and reptiles are similar.  The same assumption is used for fish and aquatic-phase amphibians.
 
 In general, categories of acute toxicity ranging from "practically nontoxic" to "very highly toxic" have been established for aquatic organisms (based on LC50 and EC50 values or limit of solubility), mammals (based on LD50 values), avian species (based on and LD50 and  LC50 values), and non-target insects (based on LD50 values for honey bees) (U.S. EPA 2001).  These categories are presented in Appendix E.
 
 	1.  Aquatic Effects  
 
 The acute and chronic toxicity reference values associated with freshwater and estuarine/marine species exposure to fluopyram are summarized in Table 15. These toxicity reference values represent the most sensitive species tested within each taxonomic group.  A more detailed summary of the aquatic toxicity data available to characterize risks associated with fluopyram applications is given in Appendix E.

For fluopyram, all fluopyram technical toxicity endpoints from aquatic studies with water column animals (freshwater and estuarine/marine fish and invertebrates), as well as benthic invertebrates, were used to quantitatively characterize potential risk resulting from exposure to spray drift and runoff / erosion.  However, toxicity endpoints from studies on aquatic organisms (fish and invertebrates) with the typical end use product (TEP) are used quantitatively to estimate risk resulting from exposure to spray drift only. See additional discussion in the Description of Assumptions, Limitations, Uncertainties, Strengths and Data Gaps  section of this document.

An additional consideration to note is that the reported solubility of fluopyram is 16 ppm or (mg a.i./L). Many of the submitted aquatic toxicity tests for fluopyram technical report a lower test chemical solubility under test conditions, and therefore the highest concentrations tested in some of the submitted aquatic studies are not up to the level of solubility reported in the available fate information for fluopyram. The formulated product appears to have a higher level of solubility based on the submitted toxicity studies. See additional discussion in the Description of Assumptions, Limitations, Uncertainties, Strengths and Data Gaps  section of this document.

 Only one study was submitted to the US EPA that examined the toxicity of fluopyram degradates to any non-target aquatic organism. An algal study with fluopyram-lactame has been submitted and is summarized below. 
 
 Table 15. Toxicity reference values for aquatic organisms exposed to fluopyram technical or formulated fluopyram (Fluopyram SC 500A, 41.5% active ingredient).
                               Exposure Scenario
                              % Active Ingredient
                                    Species 
                               Exposure Duration
                            Toxicity Reference Value
                                     Effect
                                   Reference
                                (Classification)
 Freshwater Fish
                                                                          Acute
                                      TGAI
                                     94.7%
 Rainbow Trout
 Oncorhynchus mykiss
                                    96 hours
 LC50>1.78 mg a.i./L
 NOAEC=1.78 mg a.i./L
 The reported limit of solubility for fluopyram TGAI under these test conditions is 2.0 mg/L, the nominal concentration for this limit test. No mortality or sublethal effects were observed at 1.78 mg a.i./L (mean-measured).
                                 MRID 47372328
                                   Acceptable
                                                                               
                                      TEP
                                     41.5%
 Rainbow Trout
 Oncorhynchus mykiss
                                    96 hours
 LC50 >46.4 mg a.i./L[b]
 NOAEC=1.31 mg a.i./L
 Sublethal effects included fish lying on the bottom of the test chamber, dark coloration, labored respiration, mucous secretion from intestine, surfacing, and lying on side/back.
                                 MRID 47372333
                                  Supplemental
                                                                        Chronic
                                      TGAI
                                     94.7%
 Fathead minnow Pimephales promelas
                                    33 days
 NOAEC = 0.135 mg a.i./L
 LOAEC = 0.269 mg a.i./L
 Treatment-related signs of toxicity were observed at the >=0.269 mg ai/L levels, including deformed mouth, ventral hematoma, labored respiration, surfacing, dark coloration, swollen belly, loss of equilibrium and lordosis.  
 Compared to the negative controls, a statistically-significant reduction in post-hatch survival and the growth of surviving fry occurred at the two highest treatment levels (0.560 and 1.05 mg a.i./L).
 
 
                                 MRID 47372336
                                   Acceptable
                                        
 Freshwater Invertebrates
                                                                          Acute
                                      TGAI
                                     94.7%
 Water flea
 Daphnia magna
                                    48 hours
 EC50>17 mg a.i./L
 NOAEC=17 mg a.i./L
 No immobilization or sublethal effects were observed at any treatment level.
                                 MRID 47372324
                                  (Acceptable)
                                                                               
                                      TEP
                                     41.5%
 Water flea
 Daphnia magna
                                    48 hours
 EC50>38.2 mg a.i./L
 NOAEC=11.6 mg a.i./L 
 Immobilization occurred at 20.4 mg a.i./L (13%) and 38.2 mg a.i./L (20%). 
 
 No other sublethal effects were reported.
                                 MRID 47372325
                                  (Acceptable)
                                                                        Chronic
                                      TGAI
                                     94.7%
 Water flea
 Daphnia magna
                                    21 days
 NOAEC = 1214 ug a.i./L
 LOAEC = 2996 ug a.i./L
 Offspring production was affected at the highest treatment level, 2996 ug a.i./L. Of the 836 total offspring produced at the 2996 μg ai/L level, 225 neonates were dead, and 49 of the 611 living offspring (8.0%) showed unspecified sublethal signs of toxicity. Mean body lengths of the parent daphnia were also affected at 2996 ug a.i./L.
                                 MRID 47372334
                                  (Acceptable)
 Estuarine/Marine Fish
                                                                          Acute
                                      TGAI
                                     94.7%
 Sheepshead minnow
 Cyprinodon variegatus
                                    96 hours
 LC50 >0.98 mg a.i./L[a]
 NOAEC=0.98 mg a.i./L
 No mortality or sublethal effects were observed at any treatment level.
 MRID 47372330
 (Acceptable)
                                                                        Chronic
                                        
                                    Data Gap
 Estuarine/Marine Invertebrates
                                                                          Acute
                                      TGAI
                                     94.7%
 Saltwater mysid Americamysis bahia
                                    96 hours
 EC50>0.51 mg a.i./L
 NOAEC=0.27 mg a.i./L
 Two mysids were reportedly missing from the highest treatment group, and were therefore considered dead.  
 
 No other sublethal effects were reported.
 MRID 47372327
 (Acceptable)
                                                                        Chronic
                                    Data Gap
 Freshwater Benthic Invertebrates
                                                                          Acute
                                    Data Gap
                                                                        Chronic
                                      TGAI
                                     94.7%
 
 Midge 
 Chironomus tentans
                                    54 days
 Sediment concentrations
 NOAEC = 26 mg a.i./kg sediment
 LOAEC = 48 mg a.i./kg sediment
 
 Pore water concentrations
 NOAEC = 3.8 mg a.i./L pore water
 LOAEC = 8.8 mg a.i./L pore water
 The most sensitive endpoints were larval survival (assessed on day 20) and percent emergence. These endpoints were statistically-reduced at the 48 and 96 mg TRR/kg sediment levels.  Midge growth (assessed on day 20) and development rate for both sexes were statistically-reduced at the 96 mg TRR/kg sediment level.
 MRID 47372339
 (Supplemental)
 Estuarine/Marine Benthic Invertebrates
                                                                          Acute
                                      TGAI
                                     94.7%
 Saltwater amphipod
 Leptocheirus plumulosus
                                    10 days
 Sediment value: 
 LC50 > 100 mg a.i./kg sediment
 NOAEC=100 mg a.i./kg sediment
 
 Pore water value:
 LC50 > 7.5 mg a.i./L pore water
 NOAEC = 7.5 mg a.i./L pore water
 
 Mortality was 1, 5, 6, 3 and 2% in the 5.8, 14, 26, 51 and 100 mg [14]C-AEC656948 equivalents/kg dry sediment treatment groups, respectively. 
 
 No sublethal effects observed.
 MRID 47372338
 (Acceptable)
                                                                        Chronic
                                      TGAI
                                     94.7%
 Saltwater amphipod
 Leptocheirus plumulosus
                                    28 days
 Sediment concentrations
 NOAEC = 36 mg TRR/kg sediment
 LOAEC = 92 mg TRR/kg sediment
 
 Pore water concentrations
 NOAEC = 2.5 mg TRR/L pore water
 LOAEC = 5.9 mg TRR/L pore water
 The reviewer's analysis detected a significant difference between the negative and solvent control groups for this endpoint, with significantly fewer (25%) offspring produced in the solvent control group. The dose-response for reproduction was poor.
 MRID 47372335
 (Supplemental)
 Aquatic Plants
                                                                    Algae Acute
                                                                               
                                      TGAI
                                     94.7%
 Pseudokirchneriella subcapitata
                                    96 hours
 EC50 = 4.3 mg a.i./L
 NOAEC = 1.46 mg a.i./L
 (biomass)
 Biomass was the most sensitive endpoint. Compared to the control, the percent inhibition ranged from 10-99% for cell density, 9-99% for biomass and 2-95% for growth rate. Mean-measured concentrations were <0.005 (<LOQ; controls), 0.093, 0.241, 0.584, 1.46, 3.78, and 9.53 mg a.i./L.  
 No cell abnormalities were reported.
                                 MRID 47372403
                                  (Acceptable)
                                                                               
                                      TEP
                                     41.5%
 Pseudokirchneriella subcapitata
                                    72 hours
 EC50 = 3.4 mg a.i./L
 NOAEC = 1.17 mg a.i./L
 (cell density)
 Cell density was the most sensitive endpoint. Compared to the control, the percent inhibition ranged from -18-99% for cell density and -3.4-110% for growth rate. Mean-measured concentrations were <0.002 (<LOQ; controls), 0.379, 1.17, 3.84, 12.5, and 38.65 mg a.i./L.  
 No cell abnormalities were reported.
                                 MRID 47372407
                                  (Acceptable)
                                                                               
                         Fluopyram-lactame (metabolite)
                                      94%
 Pseudokirchneriella subcapitata
                                    72 hours
 EC50 >8.87 mg a.i./L
 NOAEC = 8.87 mg a.i./L
 (for both cell density and growth rate)
 No treatment-related effects were observed at the highest level tested for either cell density or growth rate.
                                 MRID 47372418
                                  (Acceptable)
                                   Macrophyte
                                     Acute
                                      TGAI
                                     94.7%
 Duckweed
 Lemna gibba
                                     7 days
 EC50 = 2.6 mg a.i./L
 NOAEC = 0.28 mg a.i./L
 (frond number based on yield)
Frond number based on yield was the most sensitive endpoint. There were no phytotoxic effects in the first three treatment levels.  Small fronds and slight chlorosis were observed in the 4.04 mg a.i./L test concentration, while single fronds and slight to medium chlorosis were observed in the highest test concentration (8.88 mg a.i./L). 
 Based on frond number, the percent inhibition in the treated samples as compared to the negative control ranged from 1.2 to 92.9%.  Based on frond area, the percent inhibition in the treated samples as compared to the negative control ranged from -3.8 to 90%.  
                                 MRID 47372401
                                  (Acceptable)
                                        
 
                                      TEP
                                     41.6%
 Duckweed
 Lemna gibba
                                     7 days
 EC50 = 2.9 mg a.i./L
 NOAEC = 1.04 mg a.i./L
 (frond number based on yield)
The most sensitive endpoint was frond number based on yield. There were no phytotoxic effects in the first two treatment levels.  Small fronds, medium necrosis, and slight chlorosis were observed in the 4.34 mg a.i./L test concentration.  Single fronds, small fronds, and medium necrosis were observed in the 8.42 mg a.i./L treatment level.  Small fronds, medium necrosis, single fronds, and strong necrosis were observed in the highest test concentration (15.9 mg a.i./L).  
 Based on frond number, the percent inhibition in the treated samples as compared to the negative control ranged from 3.9 to 94.5%.  Based on frond area, the percent inhibition in the treated samples as compared to the negative control ranged from 9.7 to 92.2%.
                                 MRID 47372402
                                  (Acceptable)
                                        
 [a] These values were used for evaluation of risk via spray drift only.
   

Freshwater Fish
Acute freshwater fish studies with technical-grade fluopyram were conducted up to the limits of solubility determined under the specific test conditions, which ranged from ~ 2 to 5 mg a.i./L. No mortality or sublethal effects were observed at the solubility limit (1.78 mg a.i./L, mean-measured) in a 96-hour study with rainbow trout (Oncorhynchus mykiss) and fluopyram TGAI. Similar results were observed in other 96-hour studies with freshwater fish. In the acute toxicity test with bluegill sunfish (Lepomis macrochirus), no mortality or sublethal effects were observed at any treatment level (LC50 > 5.17 mg a.i./L and NOAEC = 5.17 mg a.i./L). In an acute toxicity test with fathead minnow (Pimephales promelas), the LC50 was greater than 4.95 mg ai/L and NOAEC was 4.95 mg ai/L, based on no observations of mortality or sublethal effects. All three of these acute tests are considered acceptable.  One additional acute test was submitted for a freshwater fish species, the common carp (Cyprinus carpio). However, this study is considered unacceptable (invalid) due to the presence of undissolved test material at all test levels and high variability in measured concentrations. Based on the results of submitted toxicity studies, fluopyram is considered to have little or no toxicity to freshwater fish up to the reported limits of solubility.

A study with the formulated fluopyram end-use product (Fluopyram SC 500; 41.5% active ingredient) was also conducted with the rainbow trout and the 96-hour LC50 was greater than 46.4 mg a.i./L. The calculated LC50 is based on time-weighted average concentrations. Some sublethal effects were observed and the EC50 and NOAEC values, based on sublethal effects, were 3.71 and 1.31 mg ai/L, respectively.  Sublethal effects observed throughout the test included inactivity or abnormally low activity, labored respiration, remaining on the bottom of the test vessel, dark coloration, surfacing, lying on their side or back, loss of equilibrium with lateral deviation from their normal orientation and displaying mucous excretions from the intestine. Undissolved test material was observed at the three highest treatment levels in this study. The mean of the measured test concentrations are within 88 to 98% of the nominal, implying that the undissolved test material was included in the chemical analyses. However, the bioavailability of the undissolved test material is uncertain, and therefore the study is classified as supplemental. 

An early-life stage study with fluopyram technical was also submitted for freshwater fish. Fertilized fathead minnow (Pimephales promelas) eggs/embryos (<24 hours old) were exposed to fluopyram technical for 33-days. In this study, time to hatch and hatching success were unaffected by exposure. Statistically significant larval mortality (5%) was observed at the highest treatment level (1.05 mg ai/L) only. Hatched larval survival was 100% at all other control and treatment levels on day 5 (prior to thinning). Reduction in post-hatch survival also occurred at the two highest treatment levels compared to the negative control. In addition, the growth of surviving fry was adversely affected by exposure.  Mean length and weight of the surviving fry were reduced compared to the negative control at the two highest treatment levels (0.560 and 1.05 mg ai/L). Treatment-related signs of toxicity were observed at the three highest treatment levels (>=0.269 mg ai/L) from days 20 to 33. These abnormalities included deformed mouth, ventral hematoma, labored respiration, remaining at the water surface, dark coloration, swollen belly, loss of equilibrium (with lateral deviation from normal orientation), and/or lordosis. This study was determined to be acceptable, with a NOAEC was determined to be 0.135 mg a.i./L for this study, with a LOAEC of 0.269 mg a.i./L based on observed sublethal effects. 

Freshwater Invertebrates
Toxicity tests that evaluated the effects of both technical grade fluopyram and formulated fluopyram (Fluopyram SC 500 G) to freshwater invertebrates were submitted and were found to be acceptable. Technical grade fluopyram caused no mortality or sublethal effects at any treatment level in a 48-hour test with water fleas (Daphnia magna; EC50 >17 mg a.i./L and NOAEC=17 mg a.i./L). Dimethylformamide (100 ug/1000 ml test water) was used as a solvent in this test. The 48-hour acute toxicity endpoints of the fluopyram end-use product to Daphnia magna were EC50 > 38.2 mg a.i./L and NOAEC =11.6 mg a.i./L, based on immobility. Immobility was observed at the two highest treatment levels (20.4 and 38.2 mg a.i./L) in 13 and 20 percent of the test organisms, respectively. Based on the results of these studies, fluopyram technical would be classified as practically nontoxic to freshwater invertebrates and formulated fluopyram is classified as no more than slightly toxic to Daphnia magna on an acute toxicity basis.

In a 96-hour shell deposition test with the eastern oyster (Crassostrea virginica), there was no mortality or inhibition of shell growth.  Shell growth was promoted in all treatment levels, relative to the negative control group.  The EC50 was >0.43 mg ai/L and the NOAEC was 0.43 mg ai/L. A solvent (DMF, 0.1 mL/L) was used in this study, so it is unclear why the test concentrations of fluopyram in the study are considerably lower than the reported solubility of the chemical.

Based on an acceptable 21-day chronic life cycle study with Daphnia magna, the chronic NOAEC of fluopyram technical is 1.214 mg ai/L. Treatment-related effects on offspring production and terminal body lengths of surviving females were observed at the highest treatment level (LOAEC = 2.996 mg ai/L). The 21-day EC50 for adult immobility (mortality) was >2.996 mg ai/L.

A non-guideline sub-chronic study with benthic freshwater invertebrates was also submitted. The 28-day toxicity of technical-grade fluopyram to the freshwater dipteran Chironomus riparius was studied under static conditions with aeration. First instar larvae were exposed to fluopyram via spiked water. Effects on emergence were observed at the two highest treatment levels (overlying water concentrations of 1.63 mg ai/L and 6.76 mg ai/L) and effects on development rate occurred at the highest treatment level (6.76 mg ai/L). The 28-day EC50 exceeded the highest concentration level for emergence ratio and development rate (EC50 > 5.52 mg ai/L). However, the reviewer was unable to calculate emergence ratio or discern replicate data to conduct an independent verification of the results because raw data was not submitted. Therefore, this study is currently uncategorized, pending the submission and review of the requested data.  

The chronic toxicity of fluopyram to the freshwater midge Chironomus tentans was studied during 54-day life-cycle test. The total radioactive residues (TRR) were measured in this test and include both the parent compound and any degradates. As fluopyram appears to be resistant to degradation, the TRR are considered to be approaching the actual parent compound concentrations. The NOAEC was 26 mg total radioactive residue (TRR)/kg dry sediment (corresponding with 3.8 mg TRR/L pore water), based upon statistically-significant reductions in larval survival on day 20 (17-40% reduction) and percent emergence on day 54 (26-28% reduction) compared to the negative control. These endpoints were statistically-reduced at the 48 and 96 mg TRR/kg sediment levels.  Midge growth on day 20 (26% reduction) and development rate for both sexes (25% reduction) were statistically-reduced at the 96 mg TRR/kg sediment level. No treatment-related effect on time to death for mated adults, number of eggs per female, or percent hatch of egg masses were indicated. This study is considered supplemental because it is a non-guideline study, but it provides adequate information to assess chronic risk to freshwater benthic invertebrates.

 
Estuarine/marine Fish
 An acute toxicity study for fluopyram technical was conducted on sheepshead minnow
 (Cyprinodon variegates). No mortality or sublethal effects were observed at any treatment level (LC50 > 0.98 mg a.i./L and NOAEC=0.98 mg a.i./L). Based on the results of this acceptable study, fluopyram technical is practically nontoxic to estuarine/marine fish. 
 
 No studies were submitted to examine fluopyram chronic effects on estuarine/marine fish.

Estuarine/marine Invertebrates
An acute 96-hour study with the saltwater mysid, there was 10% mortality in the highest treatment group (0.51 mg ai/L) and no mortality was detected in the lower treatment levels or controls (LC50:  >0.51 mg ai/L, NOAEC = 0.27 mg ai/L).

No studies were submitted to examine fluopyram chronic effects on estuarine/marine invertebrates in the water column.
 
A short-term 10-day study was submitted for sediment-dwelling estuarine/marine invertebrates. No treatment-related effect on survival of the marine amphipod Leptocheirus plumulosus was observed.  The data for the marine amphipod Leptocheirus plumulosus suggest that fluopyram is practically non-toxic to benthic saltwater invertebrates, as no treatment-related effect on survival were observed (LC50 >100 mg TRR/kg dw sediment and > 7.5 mg TRR/L pore water). 
 
Chronic data were also submitted for estuarine/marine benthic invertebrates. In a 28-day test with the estuarine amphipod Leptocheirus plumulosus, neonates were exposed to fluopyram-spiked sediment. The 28-day NOAEC was 36 mg TRR/kg sediment (corresponding with 2.5 mg TRR/L pore water), based upon a statistically-significant reduction in dry weight (X %) compared to the negative control at the 92 mg TRR/kg sediment level (corresponding with 5.9 mg TRR/L pore water). An effect detected in reproduction at 6.3 mg TRR/kg sediment is not considered to be treatment related due to a very poor dose-response for this endpoint. For all test levels, no treatment-related effects on survival were observed.  Offspring production was reduced at all levels (6 to 41%) and significantly so (p<0.05) at the second lowest treatment level (6.3 mg TRR/kg).  The average number of offspring per amphipod ranged from 5 to 9 for all levels. However, the dose-response for this endpoint is considered very poor as the offspring survival increased at higher concentrations and there was a high degree of variability in response. In addition, a significant difference was detected between the negative and solvent control for the reproduction endpoint, with significantly fewer offspring produced in the solvent control. The potential effect of the solvent on reproduction confounded the effect observed for this endpoint, so interpretation of these results should be made with caution. This study is considered supplemental information due to potential solvent effects on reproduction and the lack of statistical power for this endpoint (only effects 38% or above, relative to controls, would be statistically significant).
 

Aquatic Plants
Five algal toxicity studies were submitted for fluopyram technical. The results of these studies varied among species. For two species, no adverse effects were observed in the submitted toxicity studies. Specifically, in a 96-hour acute toxicity study with the saltwater diatom Skeletonema costatum, the NOAEC and EC50 values for all three endpoints (cell density, biomass and growth rate) were 1.13 and >1.13 mg a.i./L, respectively.  The results for blue-green algae Anabaena flos-aquae were similar, as no endpoint was affected by fluopyram technical at any test level (NOAEC = 9.69 mg a.i./L  and EC50  >9.69 mg a.i./L).

Other species exhibited negative effects on cell density, biomass and growth rate following exposure to fluopyram technical. In a 96-hour acute toxicity study with the freshwater diatom Navicula pelliculosa, the most sensitive endpoint was biomass, with NOAEC and EC50 values of 2.47 and 6.1 mg a.i./L, respectively.

Two studies were conducted with the freshwater green algae Pseudokirchneriella subcapitata  -  one study with the fluopyram technical and another study with the fluopyram formulated product (SC 500 G). In a 96-hour acute toxicity study, cultures of the freshwater green algae Pseudokirchneriella subcapitata were exposed to AE C656948 (Fluopyram) Technical. The most sensitive endpoint was biomass, with NOAEC and EC50 values of 1.46 and 4.3 mg a.i./L, respectively. In a 72-hour acute toxicity study, cultures of Pseudokirchneriella subcapitata were exposed to the fluopyram formulated product. The more sensitive endpoint was cell density, with NOAEC and EC50 values of 1.17 and 3.4 mg a.i./L, respectively. Based on the results of these studies, fluopyram appears to have effects on algal growth at similar levels, whether the exposure occurs in the form of the active ingredient alone or the as the formulated product. However, the duration of exposure was shorter for the study with the formulated product and the study with the formulated product was conducted with a higher light intensity than the study with the technical product (5620-7090 lux compared to 4300 lux). These factors may have influenced the results.

One algal study with Pseudokirchneriella subcapitata was submitted for the degradate fluopyram lactame, and no treatment-related effects were observed (EC50 >8.87 mg/L and NOAEC = 8.87 mg/L).

Two aquatic vascular plant studies were submitted for fluopyram, one study with the technical product and another with the formulated product (Fluopyram SC 500A). In a 7-day acute toxicity study, the freshwater macrophyte, duckweed (Lemna gibba), was exposed to fluopyram technical. The most sensitive endpoint was frond number based on yield, with NOAEC and EC50 values of 0.278 and 2.6 mg a.i./L, respectively. There were no phytotoxic effects in the first three treatment levels.  Small fronds and slight chlorosis were observed in the second highest treatment level (4.04 mg a.i./L), while single fronds and slight to medium chlorosis were observed in the highest test concentration (8.88 mg a.i./L). In another 7-day acute toxicity study, freshwater duckweed (Lemna gibba), was exposed to the formulated fluopyram product. Small fronds, necrosis and chlorosis were observed at the three highest treatment levels (4.34, 8.42, and 15.9 mg a.i./L). The most sensitive endpoint was frond number based on yield, with NOAEC and EC50 values of 1.04 and 2.9 mg a.i./L, respectively.
 
 	
 	2.  Terrestrial Effects  
 
 The acute and chronic toxicity references values associated with fluopyram exposure to terrestrial animals are summarized in Table 16. 
 
 Table 16.  Toxicity reference values for terrestrial organisms exposed to fluopyram technical or formulated fluopyram (Fluopyram SC 500A, 41.5% active ingredient). 
                               Exposure Scenario
                              % Active Ingredient
                                    Species
                               Exposure Duration
                                   Toxicity 
                                Reference Value
                                     Effect
                                   Reference
 Mammals
                                                                          Acute
TGAI
(94.7% a.i.)
 
 Laboratory Rat 
 (Rattus norvegicus) 
 Single oral dose  
 LD50 > 2000 mg a.i./kg bw
 No mortalities observed at 2000 mg/kg. No effects on weight or other gross pathological findings were reported. 
 MRID
 47372430
 
 Acceptable
                                                                       Chronic 
TGAI
 (94.7% a.i.)

 Laboratory Rat (Rattus norvegicus)
 90-day dietary study
 NOAEL = 13 mg a.i./kg bw/day 
 
 LOAEL = 61 mg a.i./kg bw/day
Decreased body weight and food consumption observed at the two highest treatment levels (61 and 204 mg a.i./kg/day for male rats, 70 and 230 mg a.i./kg day for female rats).

 MRID 47372441
 
 Acceptable
 Birds
                                                                          Acute
TGAI
 (94.5% a.i. [bobwhite]  and 94.7% a.i [zebra finch]).
 Northern bobwhite quail (Colinus virginianus) and zebra finch (Taeniopygia guttata)
 Single oral dose 
 LD50 >2000 mg a.i./kg bw
 
 
 Bobwhite quail:  Cumulative mortality was 0/9, 1/10, 1/10, and 4/10 birds from the control, 500, 1000, and 2000 mg ai/kg bw nominal treatment levels, respectively.  
 Treatment-related signs of toxicity were observed at all dose levels, including diarrhea, soft excrement, ptosis, fluffed feathers, red excrements, and reduced vigilance. Necropsy of birds that died during the study indicated severe emaciation, reduction in organ size (breast muscle, liver, spleen, heart, and/or liver) and discoloration of organs (gizzard, intestines, and/or pancreas). Therefore, the NOAEL <500 mg a.i./kg bw.
 
 Zebra finch:  Two limit tests were conducted with the zebra finch. Six birds were exposed in each individual test. In the first test, one mortality occurred. A second test was conducted and no mortalities occurred. Pilorection, ataxia, lethargy, wing droop and uncoordination were observed in the single treatment level. Therefore, the NOAEL is <2000 mg a.i./kg bw.
 MRIDs 47372341 
 Acceptable
 
 and 
 
 47567007
 Supplemental
 
                                                                          Acute
TGAI
 (95.0% a.i.)
 Northern bobwhite quail (Colinus virginianus)
 5-Day dietary 
 LC50 >4785 mg a.i./kg diet
 
 Based upon treatment-related reductions (24 to 64% of control) in food consumption at all treatment levels on day 7, the reviewer determined the NOAEC to be <279 mg ai/kg diet.  There was a statistically-significant reduction in body weight in birds from the 4785 mg ai/kg diet level during the exposure period.  No mortality, clinical signs of toxicity, or post-mortem findings were observed.
 MRID 47372343
 
 Acceptable 
                                                                        Chronic
TGAI
 (94.7% a.i.)
 Bobwhite quail
 (Colinus Virginianus) and Mallard duck (Anas platyrhynchos)
 Avian reproduction study (dietary exposure, one generation) 
 NOAEC = 46.7 mg a.i./kg diet[a]
 
 LOAEC = 75.7 mg a.i./kg diet[a]
 The NOAEC value is based on a treatment-related reduction in 14-day survivor body weight for bobwhite quail chicks (mean-measured concentrations) (MRID 47372344).  In this study, reductions in hatchling body weight and percentage of 14-day survivors/number of hatchlings were also observed at 175 mg a.i./kg diet. Other studies showed additional reproductive effects such as reductions in adult female body weight gain, reduced number of eggs laid, increased numbers of cracked or defective eggs, increased embryonic mortality, reductions in egg shell strength & thickness, and reductions in the number of hatchlings and 14-day chick survivors at higher treatment levels.
 MRIDs 47372344
 Acceptable
 
 47372345
 Supplemental
 
 47372346
 Acceptable
 Terrestrial Insects
                                                                          Acute
TGAI
 (95.5% a.i.)
 Honey bee
 (Apis mellifera)
 
 96-Hour acute contact and oral toxicity test 
 
 
 Contact toxicity
 LD50 >100 μg test material/bee
 
 Oral toxicity
 LC50 >102.3 ug test material/bee
 No mortalities or sublethal effects were observed in the controls or treatment groups for either test. 
 MRID 47372347
 
 Contact toxicity test:
 Acceptable
 
 Note:  No guideline available for acute oral toxicity to honey bees.
 
                                                                          Acute
TEP
 (41.6% a.i.)
 Honey bee
 (Apis mellifera)
 
 96-Hour acute contact and oral toxicity test 
 
 
 Contact toxicity
 LD50 > 83.2 ug a.i./bee
 
 Oral toxicity
 LC50 > 89 μg a.i./bee
 
 Contact toxicity
 1/50 mortality in the 83.2 ug a.i./bee level and no mortality in the control (5 reps of 10 bees).  
 
 Oral toxicity
 1/50 mortality in the 89 ug a.i./bee level and no mortality in the control (5 reps of 10 bees).  
 
 No sublethal effects were observed in the controls or treatment groups for either test.
 MRID 47372348
 
 Contact toxicity test:
 Acceptable
 
 Note:  No guideline available for acute oral toxicity to honey bees. 
 Plants - Tier I seedling emergence
                                                                        Monocot
TEP
 (41% a.i.)
 Oat (Avena sativa), perennial ryegrass (Lolium perenne),  barley (Hordeum vulgare) and corn (Zea mays)
 Single application at test initiation
 EC25 >0.444 lbs a.i./A
 NOAEC = 0.444 lbs a.i./A
 No detrimental effects >=25% were observed for any test species. 
 
 The highest reduction in seedling emergence for monocots was 6.3% in barley (not statistically significant) at the 0.444 lb a.i./A treatment level. The highest reduction in dry weight for monocots was 9.9% in ryegrass (not statistically significant) at the 0.444 lb a.i./A treatment level.
 MRID 47372349
 
 Acceptable
                                                                          Dicot
TEP
  (41% a.i.)
 Sugarbeet  (Beta vulgaris),  oilseed rape (Brassica napus),  soybean (Glycine max),  cucumber  (Cucumis sativus),  buckwheat  (Fagopyrum esculentum)  and sunflower (Helianthus annuus)
 Single application at test initiation
 EC25 <0.444 lbs a.i./A
 NOAEC <0.444 lbs a.i./A
 Buckwheat was the most sensitive dicot species. A significant reduction (50.4%) was observed in buckwheat dry weight at the 0.444 lbs a.i./A treatment level. 
 
 Mild inhibition in height occurred across treatments, with soybean having the highest level of inhibition of 12.1% in comparison to the control (statistically significant) at the 0.444 lbs a.i./A treatment level. Soybeans also had a statistically significant reduction in dry weight, 14.1% in comparison to the control.
 MRID 47372349
 
 Acceptable
 Plants - Tier II seedling emergence
                                                                          Dicot
TEP
(41% a.i.)
 Buckwheat
 (Fagopyrum esculentum)
 Single application at test initiation
 No acceptable endpoints available
 The most sensitive endpoint was biomass. No clear dose-dependent pattern for effects on biomass was observed due to high variance. Compared to the negative control, reductions in biomass were 12.3, 1.6, 21.3, 40.1 and 6.2% at nominal concentrations of 0.028, 0.056, 0.111, 0.222, and 0.444 lbs a.i./acre respectively. 
 
 Inhibition in height was very mild across all test concentrations. No other phytotoxic effects were reported.  
 MRID 47372349
 
 Supplemental
 Plants - Tier I vegetative vigor
                                                                        Monocot
TEP
 (41% a.i.)
 Onion (Allium cepa), oat (Avena sativa), perennial ryegrass (Lolium perenne) and corn (Zea mays)
 Single application at test initiation
 EC25 >0.222 lbs a.i./A
 NOAEC = 0.222 lbs a.i./A
 There were no detrimental effects >=25% for any test species and no species or endpoint exhibited a significant reduction in survival, dry weight or height compared to the controls. Corn showed the highest reduction in dry weight in comparison to the control (6.1%) at 0.222 lbs a.i./A, but this difference was not statistically significant.
 
 Inhibition in height was very mild across all treatments, with no species exhibiting inhibitions of 5% in comparison to the negative control.  
 MRID 47372350
 
 Acceptable
                                                                          Dicot
TEP
 (41% a.i.)
 sugarbeet (Beta vulgaris), oilseed rape (Brassica napus), cucumber (Cucumis sativus), buckwheat (Fagopyrum esculentum), soybean (Glycine max) and sunflower (Helianthus annuus)
 Single application at test initiation
 EC25 >0.222 lbs a.i./A
 NOAEC = 0.222 lbs a.i./A
 For dry weight, sugarbeet had the highest level of inhibition of 20.2% in comparison to the negative control. However, a t-test was not able to detect a significant difference between this treatment group and the control.  
 Inhibition in height was very mild across all treatments, with no species exhibiting inhibitions of 5% in comparison to the negative control.  
 MRID 
 47372350
 
 Acceptable
 
 
 Mammals
 For terrestrial mammals, one acute oral toxicity study, one acute dermal study and two acute inhalation studies were conducted with laboratory rats exposed to fluopyram TGAI (MRIDs 47372430, 47372432, 47372434 and 47372435). Several subchronic and chronic mammalian studies with fluopyram TGAI were submitted, including a 90-day dietary rat study, a 1-year dietary canine study, a chronic feeding/carcinogenicity rat study and a 2-generation reproduction rat study (MRIDs 47372441, 47372449, 47372501 and 47372447). A subchronic dietary rat study was also submitted for fluopyram-PCA (MRID 47372521). No additional information was submitted for the formulated product fluopyram 500 SC (see Appendix D for full mammalian toxicology profile). 
 
 Results of oral, dermal and inhalation toxicity studies on rats show that fluopyram TGAI is practically non-toxic to mammals on an acute basis. The acute 4-hour LC50 was determined to be greater than 2.091 mg/L and 5.1 mg/L in the two rat inhalation studies submitted for fluopyram, which indicates low toxicity via inhalation exposure. No mortality was observed in any of the studies, but sublethal effects observed in the inhalation study included slow and labored breathing, piloerection, ungroomed hair-coat, reduced motility, high-legged gait and limpness. The LD50 is greater than 2000 mg a.i./kg bw for both oral and dermal exposure routes. There were no effects on body weight gain in any of the acute studies. Based on the non-definitive endpoints available from these toxicity studies risk quotients will not be calculated.  However, predicted exposures will be compared to the highest concentrations tested to qualitatively assess risk to these species. 
 
 Chronic and reproductive studies with rats and dogs indicate that fluopyram TGAI can affect both parents and offspring at levels as low as 61 mg/kg/day. Toxicity was observed at similar levels in a chronic 1-year dietary study with dogs and a 2-generation reproduction study with rats. In the chronic dog study, decreased weight and food consumption occurred at the 66 mg/kg bw/day treatment level (NOAEL=13 mg/kg bw/day). In a 90-day rat dietary study with fluopyram, decreased body weight and food consumption were observed at 61 mg/kg bw/day (NOAEL=13 mg/kg/day).Effects observed in the 2-generation rat reproduction study included decreased body weight in the offspring (NOAEL = 15 mg/kg bw/day; LOAEL = 83 mg/kg bw/day). To assess chronic risk to mammals, EFED will use the NOAEL of 13 mg a.i./kg bw/day based on reductions in body weight and food consumption in the submitted 90-day rat dietary study. 
 
In a chronic dietary carcinogenicity study with mice, effects were observed at lower levels of exposure than the dietary and 2-generation studies with rats. The NOAEL for systemic toxicity = 4 mg/kg/day and the LOAEL for systemic toxicity = 21 mg/kg/day, based on treatment-related follicular cell hyperplasia in the thyroid gland, centrilobular to panlobular hypertrophy and hepatocellular single cell degeneration /necrosis in the liver. Because these parameters are not clearly linked to the typical ecological endpoints of survival, growth and reproduction, these endpoints were not selected for risk estimation. 
 
 Fluopyram-PCA, a metabolite of fluopyram, showed much lower toxicity than the parent compound based on a single 28-day dietary rat toxicity study. In the subchronic study with fluopyram-PCA, no treatment-related effects were observed at the highest level tested (NOAEL=1574 mg/kg/day). In similary subchronic 28-day rat and mouse dietary studies conducted with the parent compound fluopyram, treatment-related effects including decreased body weight gain and increased liver weight were observed at levels as low as 162 mg/kg/day (MRIDs 47372516 and 47372517).
 
 
 Birds
 All toxicity reference values used to assess the potential acute and chronic risks of fluopyram exposure to birds were obtained from studies using fluopyram TGAI.  
 
 The results of a two oral toxicity studies with fluopyram indicate that the chemical is practically nontoxic to avian species on an acute basis, based on mortality effects. The incidence of mortalities did not occur at a level high enough to establish an LD50 in either study (bobwhite quail LD50  > 2000 mg a.i./kg bw, MRID 47372341; zebra finch LD50 > 2000 mg a.i./kg bw, MRID 47567007). In the study conducted with bobwhite quail, mortality occurred at all treatment levels (4 out of 10 test birds died at the highest treatment level [2000 mg ai/kg bw level], while 1 out of 10 birds died in the other two lower treatments [500 mg a.i./kg bw and 1000 mg a.i./kg bw]). Slight to severe treatment-related effects on food consumption were observed at all dose levels. Body weight losses were observed in test birds at the 2000 mg ai/kg bw level. Two limit tests were conducted with the zebra finch. Six birds were exposed in each individual test. In the first test, one mortality occurred. A second test was conducted and no mortalities occurred. Pilorection, ataxia, lethargy, wing droop and uncoordination were observed in the single treatment level. Therefore, the NOAEL is <2000 mg a.i./kg bw. 
 
 Because the low mortality (<50%) in submitted acute avian tests, which did not allow determination of an LD50, acute risk quotients will not be calculated. Nonetheless, the observed mortality and sublethal effects of fluopyram and comparison to expected environmental exposure concentrations will be discussed in the risk characterization section of this document.
 
 Two submitted 5-day dietary toxicity studies are available for fluopyram. In a study with mallard duck, there were no treatment-related effects on mortality, clinical signs of toxicity, body weight, or food consumption to the tested species, mallard duck. The acute dietary LC50 was >4604 mg ai/kg diet. Based upon a notable increase in the incidences of red pancreases in surviving birds at the 4604 mg ai/kg diet level, the NOAEC was 2307 mg ai/kg diet. The acute dietary toxicity fluopyram technical to 9-day old northern bobwhite quail was also assessed. The acute dietary LC50 was >4785 mg ai/kg diet.  Based upon treatment-related reductions (24 to 64% of control) in food consumption at all treatment levels on day 7, the reviewer determined the NOAEC to be <279 mg ai/kg diet. Furthermore, there was a statistically-significant reduction in body weight in birds from the 4785 mg ai/kg diet level during the exposure period.  No mortality, additional clinical signs of toxicity, or post-mortem findings were observed. Because these studies resulted in a non-definitive LC50 endpoint, risk quotients will not be calculated. However, predicted exposures will be compared to the levels at which mortality and sublethal effects were observed to qualitatively assess dietary risk to these species. 
 
 Results of avian reproduction studies show that there is concern for exposure to fluopyram TGAI with effects seen in both parents and hatchlings. The NOAEC value for birds is 46.7 mg a.i./kg diet based on a treatment-related reduction in 14-day survivor body weight for bobwhite quail chicks in a one-generation reproductive toxicity test, with corresponding LOAEC of 75.7 mg a.i./kg diet (based on mean-measured concentrations) (MRID 47372344).  In this study, reductions in hatchling body weight and percentage of 14-day survivors/number of hatchlings were also observed at 175 mg a.i./kg diet. Other studies showed additional reproductive effects such as reductions in adult female body weight gain, reduced number of eggs laid, increased numbers of cracked or defective eggs, increased embryonic mortality, reductions in egg shell strength & thickness, and reductions in the number of hatchlings and 14-day chick survivors at higher treatment levels (MRIDs 47372345 and 47372346). To assess chronic risk to birds, the chronic NOAEC of 46.7 mg a.i./kg diet (MRID 47372344) will be used to calculate risk quotients.
 
 
 Terrestrial Invertebrates
 Results of acute contact toxicity studies with honey bees demonstrate that fluopyram TGAI is practically non-toxic to beneficial insects.  Two acute oral toxicity tests conducted with fluopyram showed the TGAI having an LD50 > 97.7 μg a.i./bee (102.3 μg test material/bee) and formulated fluopyram having an LD50 > 89 μg a.i./bee. The acute contact tests showed an LC50 > 95.5 μg a.i./bee (100 μg test material/bee) for the TGAI and an LC50 > 83.2 μg a.i./bee for the fluopyram formulation. No definitive endpoints were given in any of the acute toxicity tests with honeybees, due to lack of mortality.
 
 Additional studies with fluopyram technical and the end-use product (Fluopyram SC 500, 41.8% active ingredient) were submitted for other nontarget terrestrial invertebrates, including predatory mite (Typhlodromus pyri), rove beetle (Aleochara bilineata, springtail (Folsomia candida), soil mite (Hypoaspis aculeifer) and earthworm (Eisenia fetida). None of these studies resulted in an LC50 or EC50, as 50% mortality did not occur at the highest treatment level in any of the tests (LC50s ranged from >20.31 mg a.i./kg dw soil to >1000 mg a.i./kg dw soil for earthworms; LD50 > 801.8 mL a.i./ha for rove beetles; LC50 >415 mg a.i./kg dw soil for soil mites and springtails; LC50 >825.9 mL a.i./ha for parasitic wasp; LC50 >834.2 mL a.i./ha for predatory mite).  The highest single application rate of 0.222 lbs a.i./acre (6.84 fl oz product/acre) is equivalent to 207 mL a.i./ha. 
 
In two 14-day toxicity studies, statistically significant weight loss (10-23%) was observed in earthworms exposed to fluopyram at treatment levels >131 mg a.i./kg dw of soil. No adverse effects on mortality or growth were observed in a 28-day subchronic study with earthworms exposed to lower levels of the end-use product (1.85 to 20.31 mg a.i./kg dw soil), but a reduced number of surviving juveniles occurred at the highest treatment levels (8-23% reduction compared to the control, NOAEC = 3.27 mg a.i./kg dw soil). In the 28-day reproduction test conducted with the springtail, the test organisms were exposed to nominal application rates of 26.1 to 415 mg a.i./kg dw soil. After 28 days, significant mortality occurred (29.5-45.5%) and the number of juveniles was significantly reduced (36.5-36.9%) at the two highest treatment levels (207.5 and 415 mg a.i./kg dw soil).  
 
 The Agency does not currently assess quantitative risk to non-target terrestrial invertebrates. However, these toxicity data will be used for a qualitative evaluation in the risk characterization section. 
 
 
 Terrestrial Plants
 For terrestrial plants, Tier I seedling emergence and vegetative vigor toxicity tests showed no detrimental effects >=25% in survival, dry weight or height compared to the controls for any test species except buckwheat in the seedling emergence test (MRIDs 47372349 and 47372350). 
 
 In the vegetative vigor study, sugarbeet had the highest level of inhibition in dry weight, a 20.2% reduction in comparison to the negative control at a fluopyram application rate of 0.222 lbs a.i./A. Because this is a Tier I study and a 25% or greater adverse effect did not occur, a Tier II study is not requested. However, a t-test was not able to detect a significant difference between this treatment group and the control. 
 
 The rate applied in the Tier I seedling emergence test, 0.444 lbs a.i./A, was greater than the maximum application rate of 0.222 lbs a.i./A. Because buckwheat showed a 50.4% reduction in dry weight at 0.444 lbs a.i./A in the seedling emergence test, a Tier II test was conducted (MRID 47372349). The most sensitive endpoint was biomass. No clear dose-dependent pattern for effects on biomass was observed due to high variance. Compared to the negative control, reductions in biomass were 12.3, 1.6, 21.3, 40.1 and 6.2% at nominal concentrations of 0.028, 0.056, 0.111, 0.222, and 0.444 lbs a.i./acre respectively. 
 
A non-guideline terrestrial plant study that evaluated the pre-plant incorporated biological effects of fluopyram 500 SC was also submitted. There were no effects on plant emergence across species, except for oat and ryegrass, which experienced effects at the first two treatment levels.  Due to promotion of growth at the highest treatment level, a dose-response relationship cannot be inferred. There was no additional crop damage in any species, and there was no effect of the treatment on fresh weight across all species (EC25 >0.44 lbs a.i./A, NOAEC = 0.44 lbs a.i./A). 

Fluopyram co-formulation toxicity data 
Some toxicity data were submitted for the fluopyram products that are co-formulated with the fungicides tebuconazole, trifloxystrobin, pyrimethanil, and prothioconazole. A complete listing of the currently available ecological toxicity studies is located in Appendix D.

For the fluopyram/tebuconazole SC 400 product, eight studies were submitted that examined the effects of the co-formulation on freshwater fish, freshwater invertebrates, algae, rats, honey bees and terrestrial plants. In all aquatic studies, the fluopyram/tebuconazole product was more toxic than fluopyram technical or formulated fluopyram. This increase in toxicity appears to be tebuconazole's greater toxicity to these organisms, compared to fluopyram. For the terrestrial organisms, none of the submitted studies with fluopyram/tebuconazole resulted in definitive endpoints, either due to lack of 50% mortality for rat and honey bees or lack of a 25% adverse effect for terrestrial plants. Therefore, both fluopyram and the fluopyram/tebuconazole co-formulated product appear to have low overall toxicity to terrestrial organisms. However, no avian data was submitted.

Seven toxicity tests were submitted for the fluopyram/trifloxystrobin 500 SC product. Three aquatic studies were submitted. Based on the results of tests with freshwater fish, freshwater invertebrates and algae, the fluopyram/trifloxystrobin co-formulation has greater toxicity to these species. Like tebuconazole, this increase in toxicity appears to be due to trifloxystrobin's greater toxicity to these organisms compared to fluopyram. Also similar to tebuconazole, none of the submitted terrestrial studies with fluopyram/trifloxystrobin resulted in definitive endpoints, either due to lack of 50% mortality for rat and honey bees or lack of a 25% adverse effect for terrestrial plants. No avian data was submitted. Both fluopyram and the fluopyram/trifloxystrobin co-formulated product appear to have low overall toxicity to terrestrial organisms. 

Only limited toxicity data were available for the fluopyram/pyrimethanil 500 SC and the fluopyram/prothioconazole SC 400 products. Rat acute oral studies were submitted for both co-formulations. Based on these studies, the fluopyram/pyrimethanil and fluopyram/prothioconazole products show low toxicity to mammals, similar to fluopyram technical. No other toxicity studies were submitted for these products.
 
         I. Risk Characterization
 
 Risk characterization is the integration of exposure and effects characterization to determine the ecological risk from the use of fluopyram and the likelihood of effects on aquatic life, wildlife, and plants based on varying pesticide-use scenarios.  The risk characterization provides estimation and a description of the risk; articulates risk assessment assumptions, limitations, and uncertainties; synthesizes an overall conclusion; and provides the risk managers with information to make regulatory decisions.
 
 A.  Risk Estimation - Integration of Exposure and Effects Data  
 	
 Results of the exposure and toxicity effects data are used to evaluate the likelihood of adverse ecological effects on non-target species.  For the assessment of fluopyram risks, the risk quotient (RQ) method is used to compare exposure and measured toxicity values (refer to Appendix F).  Estimated environmental concentrations (EECs) are divided by the most sensitive acute and chronic toxicity values.  The RQs are then compared to the Agency's levels of concern (LOCs). These LOCs, summarized in Appendix F, are the Agency's interpretive policy and are used to analyze potential risk to non-target organisms and the need to consider regulatory action.  These criteria are used to indicate when a pesticide's use as directed on the label has the potential to cause adverse effects on non-target organisms. Details of all RQs are provided in Appendix G.
 
 	
       1.  Non-target Aquatic Animals and Plants  
 
To assess risk of fluopyram to non-target aquatic animals (fish and invertebrates) and plants (macrophytes and algae), surface water, pore water and sediment EECs for fluopyram were obtained from the Tier 2 model PRZM/EXAMS based on the label-recommended usage scenarios (Table 5). In all instances, this risk assessment used the highest peak (instantaneous) concentration in surface water (for water column dwellers), benthic sediment (for benthic organisms), and benthic pore water (for benthic organisms) generated from the PRZM/EXAMS model to represent acute exposure to aquatic organisms. For chronic risk, the 21-day EECs for fluopyram were compared to available aquatic toxicity data. 

 		
             a. Water Column Exposure: Acute and Chronic Risk to Animals 
 
 Fish
 For acute risk to freshwater and estuarine/marine fish species, risk quotients were not calculated because the available toxicity endpoints were not definitive (LC50 > highest test concentration). 
 
For freshwater fish, the chronic risk quotient = 0.001 (Table 17). In EFED risk assessments, endpoints which are considered to be ecologically significant are likely to lead to reductions in survival, growth and/or reproduction of fish. For the submitted early-life stage study with fathead minnow, although sublethal effects including deformed mouth, ventral hematoma, labored respiration, surfacing, dark coloration, swollen belly, loss of equilibrium and lordosis occurred at the third highest treatment level and above (>0.269 mg a.i./L), reductions in survival and growth occurred at only the two highest treatment levels (0.560 and 1.05 mg ai/L). Therefore, 0.269 mg ai/L will be used as the functional NOAEC for chronic risk quotient calculations for freshwater fish. 

A chronic risk quotient was not calculated for estuarine/marine fish, because no chronic toxicity data were submitted for this taxon and appropriate acute-to-chronic ratios could not be determined due to non-definitive acute endpoints for all aquatic taxa. 
 
 		
Table 17. Acute and chronic risk quotients (RQs) for evaluating toxic risk of fluopyram exposure to freshwater and estuarine/marine fish.  
                                       
                                   Organism
                                       
                                     LC50
                                 (ug a.i./L)
                                       
                                     NOAEC
                                 (ug a.i./L)
                                       
                                    EEC[c]
                                     Peak
                                 (ug a.i./L)
                                       
                                    EEC[d]
                                    60-Day
                                 (ug a.i./L)
                                       
                                     Acute
                                      RQ
                                  (EEC/LC50)
                                       
                                    Chronic
                                      RQ
                                  (EEC/NOAEC)
                              Freshwater fish[a]
                                   > 1780
                                      269
                                     7.31
                                     0.286
                                Not calculated
                                     0.001
                           Estuarine/marine fish[b]
                                   > 980
                                 Not available
                                     7.31
                                     0.286
                                Not calculated
                                Not calculated
 [a] Acute toxicity value is based on rainbow trout (Oncorhynchus mykiss) (LC50 >  1.78 mg a.i./L) and chronic toxicity value is based on an early life stage study with fathead minnow (Pimephales promelas) (NOAEC = 0.135  mg a.i./L).
 [b] Acute toxicity value is based on sheepshead minnow (Cyprinodon variegates) LC50 > 0.98 mg a.i./L. Chronic toxicity data were not submitted for estuarine/marine fish.    
[c] EEC values are generated from PRZM/EXAMS and represent the most conservative level of acute exposure based on proposed label rates (watermelons, spray and drip irrigation [same EECs for each], STXmelonNMC scenario). 
d EEC values are generated from PRZM/EXAMS and represent the most conservative level of chronic exposure based on proposed label rates (watermelons, drip irrigation, Florida cucumber scenario).
 
 
 Aquatic Invertebrates
 For acute risk to freshwater and estuarine/marine invertebrate species, risk quotients were not calculated because the available toxicity endpoints were non-definitive (LC50 > highest test concentration). A chronic risk quotient was calculated for freshwater invertebrates (RQ = 0.0006; Table 18). A chronic risk quotient was not calculated for estuarine/marine invertebrates, because no chronic toxicity data were submitted for this taxon and appropriate acute-to-chronic ratios could not be determined due to the lack of definitive acute toxicity endpoints. 
 
 
Table 18. Acute and chronic risk quotients (RQs) for evaluating toxic risk of fluopyram exposure to freshwater and estuarine/marine aquatic invertebrates.  
                                       
                                   Organism
                                       
                                     LC50
                                 (ug a.i./L)
                                       
                                     NOAEC
                                 (ug a.i./L)
                                       
                                    EEC[c]
                                     Peak
                                 (ug a.i./L)
                                       
                                    EEC[c]
                                    21-Day
                                 (ug a.i./L)
                                       
                                     Acute
                                      RQ
                                (peak EEC/LC50)
                                       
                                    Chronic
                                      RQ
                              (21-day EEC/NOAEC)
                          Freshwater invertebrates[a]
                                  > 17,000
                                     1214
                                     7.31
                                     0.712
                                Not calculated
                                    0.0006
                       Estuarine/marine invertebrates[b]
                                   > 510
                                 Not available
                                     7.31
                                     0.712
                                Not calculated
                                Not calculated
 [a] Acute and chronic toxicity values are based on studies with the water flea (Daphnia magna)  -  acute EC50 >  17 mg a.i./L and chronic toxicity NOAEC = 1214 ug a.i./L.
 [b] Acute toxicity value is based on saltwater mysid Americamysis bahia LC50 > 0.51 mg a.i./L. Chronic water column toxicity data were not submitted for estuarine/marine invertebrates.    
[c] EEC values are generated from PRZM/EXAMS and represent the most conservative level of acute exposure based on proposed label rates (watermelons, spray and drip irrigation [same EECs for each], STXmelonNMC scenario). 
[d] EEC values are generated from PRZM/EXAMS and represent the most conservative level of chronic exposure based on proposed label rates (watermelons, drip irrigation, Florida cucumber scenario). 
 
 
 	b. Sediment Exposure: Acute and Chronic Risk to Benthic Invertebrates 
 
 Comparisons of EECs and sediment toxicity endpoints are provided below to supplement risk estimation to water column organisms. The evaluation of toxic risk to the benthic organisms was approached by assuming equilibrium partitioning of a high Koc compound like fluopyram between the sediment and the pore water (the water found between particulates in the sediment).  Risk to benthic organisms was assessed using two approaches: (1) EECs for sediment were model-generated (PRZM/EXAMS) and compared to the toxicity value as reported for sediment exposure (EC50/LC50/NOAEC) in the sediment toxicity tests (normalized to organic carbon) and (2) EECs for pore water were model-generated (PRZM/EXAMS) and compared to the toxicity value as reported for pore water (EC50/LC50/NOAEC) in the sediment toxicity tests.  
 
 No acute risk quotients were derived for freshwater or estuarine/marine benthic invertebrates via sediment and pore water fluopyram exposure (Table 19). Short-term toxicity data were not provided for freshwater benthic invertebrates and the LC50 endpoint was undefined as no treatment  - related mortality occurred at the highest test concentration (> 2,700,000 ug a.i./kg OC; > 2500 ug a.i./L pore water) of the submitted study with estuarine/marine invertebrates. 
 
 
Table 19. Acute risk quotients (RQs) for evaluating toxic risk of fluopyram exposure to freshwater and estuarine/marine benthic invertebrates.  
                                       
                                   Organism
                                       
                               LC50 a, b, d, [f]
                               (ug a.i./kg OC)
                                     LC50
                            (ug a.i./L pore water)
                                       
                          Peak Sediment EEC c, d, [e]
                               (ug a.i./ kg OC)
                              Peak Pore Water EEC
                          (ug a.i./L pore water) [c]
                                       
                                Acute sediment
                                      RQ
                                (peak EEC/LC50)
                                       
                                    Acute 
                                  pore water
                                      RQ
                               (peak EEC/ LC50)
                          Freshwater invertebrates[a]
                                 Not available
                                 Not available
                                     63.8
                                     0.142
                                Not calculated
                                Not calculated
                       Estuarine/marine invertebrates[b]
                                > 2,700,000
                                   > 2500
                                     63.8
                                     0.142
                                Not calculated
                                Not calculated
 [a] No short-term freshwater sediment toxicity studies were submitted for fluopyram.
 [b] Acute toxicity value is based on the marine amphipod Leptocheirus plumulosus 10-day LC50 > 100 mg TRR/kg sediment and > 2.5 mg TRR/L pore water. 
 [c] EEC values are generated from PRZM/EXAMS and represent the most conservative level of exposure based on proposed label rates (watermelons, STXmelonNMC scenario). 
 [d] Sediment concentrations and toxicity endpoints were normalized to organic carbon (OC) content based on the following equation:      mg/kg OC =         mg/kg dry weight sediment     
                                                   kg TOC/kg dry weight sediment
 [e] The default organic carbon content in PRZM/EXAMS is 4% (0.04 kg TOC/kg dry weight sediment):
                 2.55 ug /kg dry weight sediment           = 63.8 ug a.i./kg OC
 	0.04 kg TOC/kg dry weight sediment
 f The sediment in the 10-day test with Leptocheirus plumulosus contained 3.7% organic carbon (0.037 kg TOC/kg dry weight sediment):
                 100,000 ug /kg dry weight sediment           = 2,700,000 ug a.i./kg OC
 	0.037 kg TOC/kg dry weight sediment
 
 
 
 Chronic risk quotients were derived for both freshwater and estuarine/marine benthic invertebrates via sediment and pore water fluopyram exposure (Table 20). 
 
 
Table 20. Chronic risk quotients (RQs) for evaluating toxic risk of fluopyram exposure to freshwater and estuarine/marine benthic invertebrates.  
                                       
                                   Organism
                                       
                             NOAEC [a,]b,  d, [f]
                               (ug a.i./kg OC)
                                     NOAEC
                            (ug a.i./L pore water)
                                       
                         21-day Sediment EEC [c, d, f]
                               (ug a.i./ kg OC)
                             21-day Pore Water EEC
                          (ug a.i./L pore water) [c]
                                       
                               Chronic sediment
                                      RQ
                              (21-day EEC/ NOAEC)
                                       
                                   Chronic 
                                  pore water
                                      RQ
                              (21-day EEC/NOAEC)
                          Freshwater invertebrates[a]
                                   1,180,000
                                     3800
                                     12.2
                                     0.027
                                    0.00001
                                   0.000007
                       Estuarine/marine invertebrates[b]
                                    643,000
                                     2500
                                     12.2
                                     0.027
                                    0.00002
                                    0.00001
 a The chronic toxicity value for freshwater benthic invertebrates is based on the midge (Chironomus tentans) 54-day NOAEC = 26 mg TRR/kg sediment and 3.8 mg TRR/L pore water.
 [b] The chronic toxicity value for estuarine/marine benthic invertebrates is based on the amphipod Leptocheirus plumulosus 28-day NOAEC = 36 mg TRR/kg sediment and 2.5 mg TRR/L pore water. 
 [c] EEC values are generated from PRZM/EXAMS and represent the most conservative level of exposure based on proposed label rates (Florida potato scenario). 
 [d] Sediment concentrations and toxicity endpoints were normalized to organic carbon (OC) content based on the following equation:      mg/kg OC =         mg/kg dry weight sediment     
                                                   kg TOC/kg dry weight sediment
 [e] The default organic carbon content in PRZM/EXAMS is 4% (0.04 kg TOC/kg dry weight sediment). 
                 0.487 ug /kg dry weight sediment           = 12.2 ug a.i./kg OC
 	0.04 kg TOC/kg dry weight sediment
 f The sediment in the 54-day test with Chironomus tentans contained 2.2% organic carbon (0.022 kg TOC/kg dry weight sediment):
                 26,000 ug /kg dry weight sediment        = 1,180,000 ug a.i./kg OC
 	0.022 kg TOC/kg dry weight sediment
   The sediment in the 28-day test with Leptocheirus plumulosus contained 5.6% organic carbon (0.056 kg TOC/kg dry   
   weight sediment):
                 36,000 ug /kg dry weight sediment        = 643,000 ug a.i./kg OC
 	0.056 kg TOC/kg dry weight sediment
 
 
 		c.  Aquatic Plants 
 
 Acute risk quotients for listed and non-listed vascular and non-vascular aquatic were calculated for the modeled crop use with the highest estimated exposure values (watermelon) for aquatic ecosystems (Table 21).
 
 Table 21.  Acute RQs for non-vascular and vascular aquatic plants exposed to fluopyram. 
                                        
                                   Plant Type
                                      EC50
                                  (μg a.i./L)
                                 NOAEC or EC05
                                  (μg a.i./L)
                       Peak Water Column EEC (μg a.i./L)
                                       RQ
                               endangered species
                              (Peak EEC/EC50) [c]
                                      RQs
                            other non-target plants
                          (Peak EEC/NOAEC or EC05) [d]
 Non-vascular plants [a]
                                      3400
                                      1170
                                      7.31
                                    0.00215
                                     0.006
 Vascular plants [b]
                                      2600
                                      278
                                      7.31
                                    0.00281
                                     0.026
 a For freshwater green algae (Pseudokirchneriella subcapitata) the EC50 = 3.4 mg a.i./L and NOAEC = 1.17 mg a.i./L based on a study with the formulated fluopyram product (41.5% active ingredient). The most sensitive endpoint was cell density.
 [b] For duckweed (Lemna gibba), the EC50 = 2.6 mg a.i./L and NOAEC = 0.278 mg a.i./L based on a study with fluopyram technical. The most sensitive endpoint was frond number based on yield.
[c] Endangered species LOC > 0.05
[d] Acute toxicity LOC > 0.5
 	
 
       2.  Non-target Terrestrial Animals  
 
 The EFED terrestrial exposure model T-REX was used to estimate exposure and risks in conservative scenarios to avian and mammalian species for four forage food types with spray applications of fluopyram as described in the Exposure Characterization. For this risk assessment, terrestrial EECs as a result of fluopyram spray applications were estimated using the maximum proposed application rate (0.222 lb a.i./A), the maximum number of applications with this rate (2), and the minimum application interval (5 days). Risk quotients were calculated using upper-bound EECs. 
 
 All toxicity reference values for terrestrial animals that are used for calculating risk quotients (RQs) are based on exposure to fluopyram TGAI and are summarized in Table 16. Dietary-based and dose-based and chronic RQs for mammals based on a maximum spray application scenario are listed in Table 22 and Table 23, respectively. . Dietary-based chronic RQs for avian species based on a maximum spray application scenario are summarized in Table 24. All chronic terrestrial RQs can be found in Appendix F.
 
 		a.  Spray Applications: Acute Risk to Birds and Mammals 
 
 Mammals
 Acute dose-based RQ values for mammalian receptors were not calculated because the results of the definitive submitted acute oral toxicity studies on mammals did not allow calculation of a definitive LD50 values. 
 
 Birds
 Acute dose- or dietary-based RQs for birds were not calculated because definitive LD50 and LC50 values were not available. 
 
             b. Spray Applications: Chronic Risk to Birds and Mammals 
 
 Mammals
 Dietary-based RQs were calculated using EECs expressed in terms of residue concentration for the various forage categories, and the toxicity value (NOAEC) is expressed in units of dietary concentration. Dose-based RQs were calculated using EECs expressed in terms of a dose concentration for the various forage categories and the estimated toxicity value (NOAEL). The dose-based EECs are calculated by using the estimated dietary concentrations and assuming the laboratory rat consumes 5% of its body weight daily. Three weight categories (or sizes) were considered for dose-based risk calculations (Tables 22 and 23).  
 	
 
 Table 22. Dietary-based chronic RQs for mammals exposed to fluopyram based on upper-bound residues on short grass, tall grass, broadleaf plants/small insects, and fruits/pods/seeds/large insects as calculated by T-REX 
                      Mammalian Chronic Risk Quotients[*]
                                  Short Grass
                                   Tall Grass
                               Broadleaf Plants/
                                 Small Insects
                               Fruits/Pods/Seeds/
                                 Large Insects
                                      7.58
                                      3.58
                                      4.39
                                      0.49
 [*] These values were calculated using the maximum application rate (0.222 lb a.i./A), the maximum number of applications (2), the minimum application interval (5 days), and a chronic NOAEC = 13 mg a.i./kg diet in rats and a default chemical foliar half-life of 35 days.
 	
 
 Table 23. Dose-based chronic RQs for small (15g), intermediate (35g), and large (1,000g) mammals exposed to fluopyram based on upper-bound residues on short grass, tall grass, broadleaf plants/small insects, fruits/pods/large insects and seeds as calculated by T-REX 
                                        
                      Mammalian Chronic Risk Quotient[*] 
                                        
                                  Body Weight
                                      (g)
                                        
                                  Short Grass
                                   Tall Grass
                               Broadleaf Plants/
                                 Small Insects
                                  Fruits/Pods/
                                 Large Insects
                                     Seeds
                                       15
                                     67.76
                                     31.06
                                     38.12
                                      4.24
                                      0.94
                                       35
                                     57.88
                                     26.53
                                     32.56
                                      3.62
                                      0.80
                                      1000
                                     31.03
                                     14.22
                                     17.45
                                      1.94
                                      0.43
 [*] These values were calculated using the maximum application rate (0.222 lb a.i./A), the maximum number of applications (2), the minimum application interval (5 days), and an estimated chronic NOAEL = 0.75 mg a.i./kg body weight/day in rats based on the chronic dietary NOAEC = 13 mg ai/kg diet and a default chemical foliar half-life of 35 days.
 			
 Birds
 For birds, chronic RQs were derived using a dietary-based chronic toxicity value. Dietary-based RQs were calculated using EECs expressed in terms of residue concentration for the various forage categories, and the toxicity value (NOAEC) is expressed in units of dietary concentration (Table 24). 
 
 
 Table 24. Dietary-based chronic RQs for birds exposed to fluopyram based on upper-bound residues on short grass, tall grass, broadleaf plants/small insects, and fruits/pods/seeds/large insects as calculated by T-REX 
                        Avian Chronic Risk Quotients [a]
                                  Short Grass
                                   Tall Grass
                               Broadleaf Plants/
                                 Small Insects
                               Fruits/Pods/Seeds/
                                 Large Insects
                                      2.17
                                      1.00
                                      1.22
                                      0.14
 [a] These values were calculated using the maximum application rate (0.222 lb a.i./A), the maximum number of applications (2), the minimum application interval (5 days), and a chronic NOAEC = 46.70 mg a.i./kg diet in bobwhite quail and a default chemical foliar half-life of 35 days.
 		
 
 	3.  Non-target Terrestrial and Semi-Aquatic Plants 						
 
 A preliminary run of TERR-PLANT was conducted using the maximum application scenarios for ground application (labeled use rates for watermelons) and aerial application (labeled use rates for almond, pecan, pistachios and tree nuts). All EECs ranged from 0.002 (spray drift) to 0.047 (semi-aquatic areas) lbs a.i./A for ground application and from 0.011 (spray drift) to 0.055 (semi-aquatic areas) lbs a.i./A for aerial application. 
 
 Compared to the available toxicity studies, in the vegetative vigor study, sugarbeet had the highest level of inhibition in dry weight, a 20.2% reduction in comparison to the negative control at a fluopyram application rate of 0.222 lbs a.i./A. The rate applied in the Tier I seedling emergence test, 0.444 lbs a.i./A, was greater than the maximum application rate of 0.222 lbs a.i./A. Because buckwheat showed a 50.4% reduction in dry weight at 0.444 lbs a.i./A in the seedling emergence test, a Tier II test was conducted (MRID 47372349). The most sensitive endpoint was biomass. No clear dose-dependent pattern for effects on biomass was observed due to high variance. Compared to the negative control, reductions in biomass were 12.3, 1.6, 21.3, 40.1 and 6.2% at nominal concentrations of 0.028, 0.056, 0.111, 0.222, and 0.444 lbs a.i./acre respectively. 
 
 
 B.  Risk Description - Interpretation of Direct Effects  

 The purpose of the risk description is to characterize risk and incorporate other lines of evidence including non-standard methods and data.
 
 
       1.  Risks to Aquatic Organisms  
 
  
 		a.  Aquatic Animals and Plants:  Water Column Exposure 
 
 Acute Risk to Fish and Aquatic-phase Amphibians
 For acute risk to freshwater and estuarine/marine fish species (and aquatic-phase amphibians using the surrogate species approach), risk quotients were not calculated because the available toxicity endpoints were non-definitive (LC50 > highest test concentration). However, as shown in Table 13, the peak estimated exposure concentration for aquatic organisms (7.31 ug a.i./L) is more than two orders of magnitude less than the highest tested fluopyram technical concentrations in acute toxicity tests that caused no adverse effects to freshwater and estuarine/marine fish species (LC50 > 0.98 mg a.i./L and NOAEC = 0.98 mg a.i./L for sheepshead minnow; LC50 >1.78 mg a.i./L and NOAEC = 1.78 mg a.i./L for rainbow trout). No mortality or sublethal effects were observed in acute fish studies with the fluopyram active ingredient. In studies with the formulated product (fluopyram 500 SC, 41.5% active ingredient), sublethal effects at the 8.27- 46.4 mg ai/L treatment groups included fish lying on the bottom of the test chamber, dark coloration, labored respiration, mucous secretion from intestine, surfacing, and lying on side/back (NOAEC =1.31 mg a.i./L). However, these effects were observed at much higher concentrations than is expected to occur in the environment.
 
 Acute risk to freshwater and saltwater fish from fluopyram use is expected to be low.
 
 
 Chronic Risk to Fish and Aquatic-phase Amphibians
 The level-of-concern for chronic risk to aquatic organisms (LOC > 1.0) was not exceeded for freshwater fish (and aquatic-phase amphibians using the surrogate species approach) (RQ = 0.001; Table 17). A chronic risk quotient was not calculated for estuarine/marine fish, because no chronic toxicity data were submitted for this taxon and appropriate acute-to-chronic ratios could not be determined due to lack of available data on definitive acute toxicity endpoints for any aquatic taxa. 
 
 Chronic risk to fish species resulting from the proposed uses of fluopyram appears to be low. Because the expected exposure concentration of fluopyram (60-day EEC = 0.286 ug a.i./L) is much lower than the levels at which adverse chronic effects to fish are expected to occur (NOAEC =  0.135 mg a.i./L and LOAEC = 0.269 mg a.i./L for fathead minnow), the submission of a fish full life cycle test or additional chronic testing with estuarine/marine fish is not expected to greatly influence the overall risk picture for fluopyram.
 
 
 Acute Risk to Aquatic Invertebrates
For acute risk to freshwater and estuarine/marine invertebrate species, risk quotients were not calculated because the available toxicity endpoints were non-definitive (LC50 > highest test concentration). However, as shown in Table 18, the peak estimated exposure concentration for aquatic organisms (7.31 ug a.i./L or 0.00731 mg a.i./L) is at least two orders of magnitude less than the highest tested fluopyram concentrations in the available acute toxicity tests, ranging from 0.51 mg a.i./L to 38.2 mg a.i./L, in which no EC50 values were definitively calculated due to low mortality.  
 
No immobility (assumed to be equivalent to death) or sublethal effects were observed in tests with technical grade fluopyram and water flea (Daphnia magna; EC50 >17 mg a.i./L and NOAEC=17 mg a.i./L). However, immobility was observed at the two highest treatment levels (20.4 and 38.2 mg a.i./L) in a Daphnia magna test with fluopyram end-use product (EC50 > 38.2 mg a.i./L and NOAEC =11.6 mg a.i./L). In addition, the submitted acute study with the saltwater mysid resulted in 10% mortality in the highest treatment group, 0.51 mg ai/L (LC50:  >0.51 mg ai/L, NOAEC = 0.27 mg ai/L). Nonetheless, the peak estimated exposure concentration for aquatic organisms (7.31 ug a.i./L or 0.00731 mg a.i./L; Table 13) is still two orders of magnitude less than the level at which immobility was observed in the these aquatic invertebrate tests. Therefore, based on currently available information, acute risk to aquatic invertebrate species due to water column exposure appears to be low following application of fluopyram from the proposed uses.
 
 
 Chronic Risk to Aquatic Invertebrates
 The level-of-concern for chronic risk to aquatic organisms (LOC > 1.0) was not exceeded for freshwater invertebrates (RQ = 0.0006; Table 17). 
 
 A chronic risk quotient was not calculated for estuarine/marine invertebrates, because no chronic toxicity data were submitted for this taxon and appropriate acute-to-chronic ratios could not be determined due to the lack of definitive acute toxicity endpoints for any aquatic species. One additional way to approximate toxicity to this taxon is to use the available chronic estuarine/marine benthic invertebrate toxicity endpoint based on pore water concentrations and compare this chronic exposure concentrations in the water column. This approach assumes that equal toxicity exists for water column and benthic invertebrates. This assumption is employed in the equilibrium partitioning (EqP) approach (Di Toro et al, 1991) when deriving sediment benchmarks when only data for water column species is available (US EPA, 2005 and US EPA, 2002). Chronic data on fluopyram were submitted for estuarine/marine benthic invertebrates. The EEC is 0.712 ug a.i./L  for the use scenario with the highest 21-day water column estimated exposure (watermelon) (Table 11). In a 28-day test with the estuarine amphipod Leptocheirus plumulosus, the NOAEC was 2.5 mg TRR/L pore water (or 2500 ug a.i./L), and the total toxic residues are assumed to be predominantly the parent chemical fluopyram. The highest chronic water column EEC (Table 12) is approximately four orders of magnitude less than the estuarine/marine benthic invertebrate NOAEC based on pore water concentrations. Some uncertainty are inherent in this comparison, due to differences in exposure routes of the toxicity tests, water-column only exposure vs. sediment ingestion in combination with pore water, as well as the life histories of the organisms. In addition, the study was considered supplemental due to the lack of a clear dose-response for reproductive endpoints. However, in the absence of additional data, this is considered the best available approximation for chronic risk to estuarine/marine invertebrates.
 
 Based on these lines of evidence, low chronic risk is presumed for aquatic invertebrates in the water column.
 
 
 Aquatic Plants
 
No acute risk quotients for non-vascular or vascular aquatic plants exceeded any of the levels-of-concern (1.0) for the modeled crop use with the highest estimated exposure values (watermelons) (Table 21). Risk quotients ranged from 0.00215 to 0.0263. The most sensitive endpoints for vascular and nonvascular plants were similar.

Two of the four algal species in toxicity studies submitted for fluopyram technical showed no adverse effects were  observed at any test level (Skeletonema costatum, NOAEC=1.13 and EC50 >1.13 mg a.i./L; Anabaena flos-aquae, NOAEC = 9.69 mg a.i./L and EC50  >9.69 mg a.i./L). Other species exhibited negative effects on cell density, biomass and growth rate following exposure to fluopyram technical (Navicula pelliculosa, the NOAEC = 2.47 and EC50 = 6.1 mg a.i./L; Pseudokirchneriella subcapitata NOAEC = 1.46 and EC50 = 4.3 mg a.i./L). 

In addition to studies with fluopyram technical, Pseudokirchneriella subcapitata was exposed to the fluopyram formulated product (NOAEC = 1.17 mg a.i./L and EC50 = 3.4 mg a.i./L). Based on the results of these studies with the same species, fluopyram appears to have effects on algal growth at similar levels, whether the exposure occurs in the form of the active ingredient alone or the as the formulated product. However, the duration of exposure was shorter for the study with the formulated product, 72 hours compared to the 96 hour duration of the test with fluopyram technical. In addition, the test with the formulated product was conducted with a higher light intensity, 5620-7090 lux compared to 4300 lux in the test with fluopyram technical. The higher light intensity likely did not change the chemical concentrations, as fluopyram degrades relatively slowly by aqueous photolysis (t(1/2)= 57 days; MRID 47372307). In addition, Time 0 measured concentrations yielded recoveries of 93 to 98% of the nominal test concentrations, and day 4 measured concentrations yielded recoveries of 88 to 95% of nominal, which indicate that fluopyram technical was relatively stable under the test conditions. However, the higher light intensity may have created differences in the rate of algal growth between the tests. Both study duration and light intensity are factors that create sources of uncertainty in directly comparing the results of the two tests. 

Both a study with the technical product and the formulated product (Fluopyram SC 500A) were submitted for freshwater duckweed (Lemna gibba). In the acute study with fluopyram technical, the NOAEC = 0.278 mg a.i./L and EC50 = 2.6 mg a.i./L, respectively. In another acute toxicity study with freshwater duckweed exposed to the formulated fluopyram product, the endpoints were similar to those observed in the study with the technical product, with a NOAEC = 1.04 and EC50  = 2.9 mg a.i./L, respectively. Small fronds, necrosis and chlorosis were observed in both studies, at higher treatment levels ranging from 4.04 to 15.9 mg a.i./L. 

In addition to studies conducted on the parent compound, one algal study with Pseudokirchneriella subcapitata was submitted for the degradate fluopyram lactame which showed low toxicity of this degradates to nonvascular plant species (EC50 >8.87 mg/L and NOAEC = 8.87 mg/L).
 
 
 

 		b.  Aquatic Animals:  Sediment Exposure 
 
 Fluopyram shows the potential to bind to particulate and organic carbon (with a high log Kow = 3.314, although the log Koc = 439 is not particularly high), which increases the likelihood of occurrence of this chemical in sediment. Exposure to this sediment can result in a direct impact to aquatic life through respiration, ingestion, dermal contact, as well as indirect impact through alterations of the food chain. Coupled with fluopyram's expected persistence in aerobic and anaerobic environments, sediment-bound fluopyram could present a toxicity risk for benthic and epibenthic aquatic life, and aquatic ecosystems in general.  Therefore, risk to benthic organisms was considered in addition to risk to water-column dwelling organisms. 
 
 No acute risk quotients were derived for freshwater or estuarine/marine benthic invertebrates via sediment and pore water fluopyram exposure (Table 19). Short-term toxicity data was not provided for freshwater benthic invertebrates and the LC50 endpoint was undefined (> 2,700,000 ug a.i./kg OC; > 2500 ug a.i./L pore water) in the submitted study with estuarine/marine invertebrates. Based on information in the available, the predicted environmental concentrations for the modeled crop use with the highest peak aquatic EEC value (watermelons) are more than four orders of magnitude lower than the highest fluopyram levels tested that did not elicit adverse effects on the survival of estuarine/marine benthic invertebrates.  The EqP approach, as described above in the water column exposure section, was also used to approximate acute risk to freshwater benthic invertebrates, as no toxicity studies were submitted for this taxon. The levels at which no adverse effects were observed acute water column toxicity tests with freshwater invertebrate (EC50>17 mg a.i./L) is 5 orders of magnitude greater than the predicted maximum peak pore water concentrations (0.142 ug a.i./L pore water). Therefore, overall acute risk to freshwater and estuarine/marine benthic organisms is expected to be low. In addition, no chronic levels-of-concern were exceeded and chronic risk to freshwater or estuarine/marine benthic invertebrates is not expected from current proposed uses of fluopyram (Table 20).
 
    
       3.  Risks to Terrestrial Organisms   
 		
             a.  Spray Applications: Acute and Chronic Risk to Birds and Mammals 
 
 Acute Risk to Birds, Reptiles and Terrestrial-phase Amphibians
 Risk quotients were not calculated for acute risk to birds (and reptiles and terrestrial-phase amphibians using the surrogate species approach) based on the nondefinitive endpoints in the submitted acute and dietary studies (LD50 > 2000 mg ai/kg bw; LC50 > 4785 mg ai/kg bw). However, mortality and sublethal effects were noted. In the acute oral study with bobwhite quail, mortalities were observed in all treatment levels, ranging from 1/10 birds at 500 mg ai/kg bw (lowest treatment level) and 4/10 birds at the 2000 mg ai/kg bw (highest treatment level. In addition, One mortality was also observed in the limit test with zebra finch (1/6 birds). A second test was conducted and no mortality occurred. However, sublethal clinical effects such as ataxia, piloerection, wing droop and uncoordination were observed in the limit test.
 
 In the dietary tests, there were no treatment-related effects on mortality, clinical signs of toxicity, body weight, or food consumption to the tested species, mallard duck (dietary LC50 >4604 mg ai/kg diet). However, based upon a notable increase in the incidences of red pancreases in surviving birds at the 4604 mg ai/kg diet level, the NOAEC was 2307 mg ai/kg diet (note that this effect does not appear to be directly linked to the typical US EPA ecological risk assessment endpoints of survival, growth or reproduction of an organism). In a study with northern bobwhite, exposure to fluopyram technical resulted in a dietary LC50 >4785 mg ai/kg diet.  Based upon treatment-related reductions in food consumption at all treatment levels, the NOAEC <279 mg ai/kg diet. A statistically-significant reduction in body weight also occurred in birds from the 4785 mg ai/kg diet level during the exposure period. 
 
For the highest use scenario (watermelons and strawberries), the most conservative acute dose-based and dietary EECs for birds would be 101.54 ppm (short grass) and 115.64 ppm (15-gram bird, short grass), respectively (assuming the default 35-day half-life). Therefore, these observations of mortality and sublethal effects occurred at levels that are approximately 2.7 to 4.3 times higher than the upper bound EECs of the highest fluopyram use scenario. Some uncertainty exists in defining the lowest level at which mortality or sublethal effects would occur, since no NOAEC was established in the most sensitive acute oral and dietary studies. Therefore, acute risk to avian species cannot be entirely precluded.
 
 
 Chronic Risk to Birds, Reptiles and Terrestrial-phase Amphibians 
 The dietary-based chronic RQs for avian species (and reptiles and terrestrial-phase amphibians using the surrogate species approach) exceed the chronic risk LOC (EEC/NOAEC >= 1) for three of the four dietary items (short grass, tall grass and broadleaf plants/small insects). The dietary-based chronic avian RQs for the fruits/pods/seeds/large insects dietary category did not exceed the chronic risk level of concern (RQ range = 0.14 to 2.17; Table 24). Therefore, chronic risk concerns exist for avian species. Potential chronic effects to avian species, such as reduction in 14-day survivor body weight for chicks, could occur at environmentally-relevant exposure concentrations of fluopyram following proposed label use rates. 
 
 Exceedances of the chronic levels-of-concern for this taxa occurred for all crops on the proposed label, with the exception of cherry (see detailed risk quotients in Appendix F).
 
 
 Acute Risk to Mammals
 Results of oral toxicity study conducted on rats show that fluopyram TGAI is practically non-toxic to mammals on an acute basis (LD50 > 2000 mg a.i./kg bw). No mortality or sublethal effects were observed in this study.
 
For the highest use scenario (watermelons and strawberries), the most conservative acute dose-based EEC for mammals is 96.81 ppm (15-gram mammal, short grass), assuming the default 35-day half-life. The highest fluopyram concentration in the acute oral study with rats did not result in any mortality or sublethal effects and is approximately 20 times greater than the highest EEC predicted for the most conservative use scenario. Therefore, acute dose-based risk to mammalian species is presumed to be low.
 
 
 Chronic Risk to Mammals
 For the maximum application scenario considered in this risk assessment (watermelons and strawberries), dietary-based RQs for chronic risk to mammalian species are above the chronic risk level-of-concern (EEC/NOAEC >= 1) for three of the four dietary items (short grass, tall grass and broadleaf plants/small insects). The dietary-based chronic mammalian RQs for the fruits/pods/seeds/large insects dietary category did not exceed the chronic risk level of concern (RQ range = 0.49 to 7.81; Table 22).
 
 Dose-based RQs for chronic risk to mammalian species exceed the chronic LOC for all dietary routes of exposure with the exception of seeds (overall RQ range = 0.43 to 67.76; Table 23).  Specifically, chronic RQs exceed the LOC for all size classes of mammals feeding on short grass (RQ range = 31.03 to 67.76), tall grass (RQ range = 14.22 to 31.06), broadleaf plants/small insects (RQ range = 17.45 to 38.12) and fruits/pods/large insects (RQ range = 1.94 to 4.24). The chronic LOC is not exceeded for mammals of any size feeding on seeds (RQ range = 0.43 to 0.94).
 
 Exceedances of the chronic levels-of-concern for this taxa occurred for all crops on the proposed label (see detailed risk quotients in Appendix F).
 
 Based on this analysis, the potential for chronic adverse affects to mammalian species could occur at environmentally-relevant exposure concentrations. These potential effects include decreased body weight in adults and offspring, as well as reduced food consumption.
 
 
 		b.  Non-target Terrestrial Invertebrates 
 
 US EPA does not evaluate the potential exposure of terrestrial insects to pesticides or quantitatively evaluate risk to this taxonomic group in new chemical screening level assessments. The risk characterization for terrestrial insects and mites that follows below is based solely on available toxicity data. 
 	
 Results of the submitted acute toxicity studies demonstrate that fluopyram TGAI and the fluopyram formulated product show little toxicity to honey bees on an acute contact or oral basis (acute oral:  LD50 > 97.7 μg a.i./bee for fluopyram TGAI and LD50 > 89 μg a.i./bee for formulated fluopyram ; acute contact:  LC50 > 95.5 μg a.i./bee for fluopyram TGAI and an LC50 > 83.2 μg a.i./bee for formulated fluopyram).
 
 Additional studies with fluopyram technical and the end-use product (Fluopyram SC 500, 41.8% active ingredient) were submitted for other nontarget terrestrial invertebrates, including predatory mite (Typhlodromus pyri), rove beetle (Aleochara bilineata, springtail (Folsomia candida), soil mite (Hypoaspis aculeifer) and earthworm (Eisenia fetida). None of these studies resulted in an LC50 or EC50, as 50% mortality did not occur at the highest treatment level in any of the tests (LC50s ranged from >20.31 mg a.i./kg dw soil to >1000 mg a.i./kg dw soil for earthworms; LD50 > 801.8 mL a.i./ha for rove beetles; LC50 >415 mg a.i./kg dw soil for soil mites and springtails; LC50 >825.9 mL a.i./ha for parasitic wasp; LC50 >834.2 mL a.i./ha for predatory mite).  The highest single application rate of 0.222 lbs a.i./acre (6.84 fl oz product/acre) is equivalent to 207 mL a.i./ha, which is lower than the highest levels tested in comparable units. Therefore, acute toxicity to these additional nontarget terrestrial invertebrates appears to be low.
 
In two 14-day toxicity studies, statistically significant weight loss (10-23%) was observed in earthworms exposed to fluopyram at treatment levels >131 mg a.i./kg dw of soil. No adverse effects on mortality or growth were observed in a 28-day subchronic study with earthworms exposed to lower levels of the end-use product (1.85 to 20.31 mg a.i./kg dw soil), but a reduced number of surviving juveniles occurred at the highest treatment levels (8-23% reduction compared to the control, NOAEC = 3.27 mg a.i./kg dw soil). In the 28-day reproduction test conducted with the springtail, the test organisms were exposed to nominal application rates of 26.1 to 415 mg a.i./kg dw soil. After 28 days, significant mortality occurred (29.5-45.5%) and the number of juveniles was significantly reduced (36.5-36.9%) at the two highest treatment levels (207.5 and 415 mg a.i./kg dw soil). Based on submitted terrestrial field dissipation studies, the maximum soil concentration following fluopyram application at 0.446 lb a.i/A (twice the maximum label rate) is 286 ug a.i./kg soil (MRIDs 47567001, 47567002, 47567003, 47567004 and 47567005). This maximum empirical soil concentration is approximately 1-3 orders of magnitude less than the exposure concentrations that caused adverse reproductive effects in the studies with earthworms and springtails. Therefore, the potential for adverse effects to soil-dwelling invertebrates following fluopyram application appears to be low, based on the currently available information.

 
 		c.  Terrestrial Plants 
 
 The maximum modeled EECs ranged from 0.002 (spray drift) to 0.047 (semi-aquatic areas) lbs a.i./A for ground application and from 0.011 (spray drift) to 0.055 (semi-aquatic areas) lbs a.i./A for aerial application. Compared to the available toxicity studies, in the vegetative vigor study, sugarbeet had the highest level of inhibition in dry weight, a 20.2% reduction in comparison to the negative control at a fluopyram application rate of 0.222 lbs a.i./A. Therefore, it does not appear as if fluopyram spray applications will have any direct phytotoxic effects on the height or weight of exposed monocot or dicot species at these proposed label rates.
 
 The rate applied in the Tier I seedling emergence test, 0.444 lbs a.i./A, was greater than the maximum application rate of 0.222 lbs a.i./A. Because buckwheat showed a 50.4% reduction in dry weight at 0.444 lbs a.i./A in the seedling emergence test, a Tier II test was conducted (MRID 47372349). The most sensitive endpoint was biomass. No clear dose-dependent pattern for effects on biomass was observed due to high variance. Compared to the negative control, reductions in biomass were 12.3, 1.6, 21.3, 40.1 and 6.2% at nominal concentrations of 0.028, 0.056, 0.111, 0.222, and 0.444 lbs a.i./acre respectively. Therefore, it appears as if some reduction in biomass following seedling emergence of certain dicot species, such as buckwheat, may occur at environmentally relevant concentrations of fluopyram exposure following the proposed spray application rates.
 
 
       4.  Review of Incident Data  
 
 Because fluopyram has not been previously approved for use in the United States, there are no incident reports for this chemical.
 
 	
 	5.  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 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 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 fluopyram, the potential direct effects to listed species should they co-occur with application sites are indicated for mammals and birds (based on consumption of short grass, tall grass and broadleaf plants/small insects).  
 
 Screening-level chronic RQs for avian and mammalian species exceed the chronic endangered species risk LOCs. In addition, acute risk to avian species could not be discounted. Listed species LOCs are not exceeded for any other taxonomic group assessed (aquatic animals, terrestrial or aquatic plants, nontarget invertebrates).  For the maximum proposed fluopyram 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 plants
 
A spatial co-occurrence analysis would be necessary to delineate the action area. 
 
 
 C.  Description of Assumptions, Limitations, Uncertainties, Strengths and Data Gaps  
 
       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 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.  However, if there are conditions under which there is more than one growing season for a crop within a single year, exposure estimates and risk to aquatic and terrestrial organisms could be significantly underestimated.  
   
       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 fluopyram, 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 aquatic risk assessment.  
  
 ::	The frequency at which actual fluopyram 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 fluopyram, given available data and model limitations.	
 
 ::	Although there are uncertainties associated with using the standard PRZM/EXAMS runoff scenario (10 ha field draining into 20,000 m[3] pond with no outlet) for an aquatic exposure assessment, it is designed to represent pesticide exposure from an agricultural watershed impacting a vulnerable aquatic environment.  Extrapolating the risk conclusions from this standard pond scenario may either underestimate or overestimate the potential risks.
 
 ::	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 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: 20,000m[3].  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 no averaging time for exposure.  A peak concentration, with a 1 in 10 year return frequency, is assumed.  The use of the peak concentration in the calculation of risk quotients assumes 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.
 
 
       3.  Exposure for Terrestrial Species 
 
 This risk assessment relies on the best available estimates of environmental fate and physicochemical properties, maximum application rate of fluopyram, 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.  
 
 Choice of Half-life Value Used in Terrestrial Exposure Modeling
 One source of uncertainty for the terrestrial risk assessment relates to the magnitude of the estimated exposure concentrations representing terrestrial exposure to fluopyram is based on a 35-day foliar dissipation half-life. When data are absent, US EPA assumes a 35-day foliar dissipation half-life as an input to T-REX model. The use of the 35-day half-life is based on the highest reported value (36.9 days) on the foliar dissipation rate of a wide range of pesticides, as reported in Willis and McDowell (1987). 
 
Some data were submitted by the registrant regarding the foliar dissipation half-life. These magnitude of residue studies were conducted on different crops than those on the proposed label. Residue decline trials were conducted on corn, sorghum, wheat, cabbage, mustard greens, lettuce, spinach, radish, sugar beet, turnip, soybean, Bermuda grass and timothy grass (MRIDs 47372606, 47567010, 47567011, 47567014, 47567015, 47567016, 47567025 and 47567026). Because the tested crops differ from the crops on the proposed label, these studies were not submitted to or reviewed by the Health Effects Division, as is typical for foliar dissipation studies. A summary of the data (MRID 47567008) and the individual study reports were preliminarily reviewed by the Environmental Fate and Effects Division. The residue trials report fluopyram concentrations following a single foliar application of fluopyram 500 SC at the maximum allowable rate (reported to be 0.223 lbs a.i./A which is slightly higher than the 0.222 lbs a.i/A used for modeling, presumably due to rounding differences). Fluopyram concentrations were analyzed in the homogenized above-ground foliage, and extracted residues were quantified using high performance liquid chromatography-electrospray ionization/tandem mass spectrometry. Sampling occurred at day 0 and four additional time points until day 10-28 post-application, depending on the study. All residue trials were conducted in typical growing areas for the examined crop. Half-lives were calculated assuming a first-order decay rate.

One potential concern exists for using the empirical half-lives from the trials. Rainfall and/or sprinkler irrigation occurred in all of the trials to varying degrees, ranging from 0.1 to 11.5 inches rainfall and 0.99 to 2.50 inches of irrigation water. When precipitation occurs, this can reduce the residues present on plant surfaces. Regardless, an additional analysis was conducted to explore how changes in the half-life used in terrestrial exposure modeling may affect risk conclusions.
 
 Based on this information, it appears that the foliar dissipation half-life could be lower than the default value of 35 days, and the terrestrial EECs may be overestimated to some degree. The range of half-lives calculated from the field trials ranged from 0.76 to 9.27 days, with the exception of an estimated half-life of 45.6 days in one trial with corn. In addition to appearing to be an outlier in the data set, the concentrations in this corn trial were highly variable and suggest that the results are questionable. From the available data in the 15 other field trials, excluding the suspect corn trial, the 90[th] percentile of the mean half-life values was calculated. This alternate half-life value for fluopyram is 7.37 days (Note:  If the 45.6 half-life value from the corn trial is added to the data set, the 90[th] percentile of the mean changes slightly to a half-life value of 8.45 days). This differs slightly from the suggested value in the summary report, 4.08 days, which is based on the overall mean of the 15 trials.
 
 The highest use scenario, the lowest use scenario, and the scenario with the greatest number of applications were run again in T-REX using 7.37-day dissipation half-life, in addition to the 35-day half-life used to calculate risk quotients. The highest and lowest use scenarios were used to bound potential exposure and risk estimates. When multiple applications are modeled, residue concentrations resulting from the final application and remaining residue from previous applications are summed. The maximum concentration calculated (out of the 365 days) is the EEC used to estimate potential risk to birds and mammals. Therefore, the number of applications is an important consideration for comparing estimated exposure based on potential differences in the half-life of a chemical. To account for the influence, the scenario with the highest number of applications was also included in this comparison. 
 
 Based on this exploratory analyses, EECs are reduced by approximately 15% of those calculated using a 35-day half-life when a 7.37-day half-life is used for the maximum and minimum use scenario. For the use scenario with the highest number of applications, EECs are reduced by about 25% when a 7.37-day half-life is used instead of the default 35 days. Despite these reductions in EECs, using a 7.37-day half-life would still result in chronic dietary-based exceedances for birds (RQs range from 0.05 to 1.85) and mammals (RQs range from 0.15 to 6.77) (Table 25-27).  This comparison suggests that even if the foliar dissipation half-life for fluopyram is the lower value reported in the residue decline trials, the chronic risks to birds and mammals as a result fluopyram exposure would remain similar. 
 
 Table 25.  Terrestrial EECs (ppm) estimated for fluopyram use scenarios with 35-day and 7.37-day foliar dissipation half-lives using upper-bound Kenaga values 
                                        
                          Watermelons and Strawberries
                            max exposure scenario[a]
                                   Cherries 
                            min exposure scenario[b]
                                    Potatoes
                scenario with highest number of applications[c]
                                  Forage Type
                                        
                                35-day half-life
                               7.37-day half-life
                                35-day half-life
                               7.37-day half-life
                                35-day half-life
                               7.37-day half-life
                                  short grass
                                     101.54
                                     86.57
                                     42.08
                                     35.88
                                     60.19
                                     44.50
                                   tall grass
                                     46.54
                                     39.68
                                     19.29
                                     16.44
                                     27.59
                                     20.39
                       broadleaf plants and small insects
                                     57.11
                                     48.70
                                     23.67
                                     20.18
                                     33.86
                                     25.03
                           fruits/pods/large insects
                                      6.35
                                      5.41
                                      2.63
                                      2.24
                                      3.76
                                      2.78
 [a]  The maximum application rate for watermelons and strawberries is 0.222 lbs a.i./A, with a 5-day application interval and 2 applications.
 [b] The maximum application rate for cherries is 0.092 lbs a.i./A, with a 5-day application interval and 2 applications. This scenario for cherries results in the lowest EECs from any of proposed application rates for any crop on the Fluopyram 500 SC label. All scenarios for terrestrial modeling use the maximum application rate for any given use pattern. Therefore, these numbers represent the exposure from the maximum application rate for the crop with the lowest proposed use rates of fluopyram. 
 [c] The maximum aerial application rate for potatoes is 0.092 lbs a.i./A, with 5-day application interval and 3 applications. The aerial scenario for potatoes has the highest number of applications for any crop on the Fluopyram 500 SC label.
 
 
 Table 26.  Chronic avian dietary RQs estimated for fluopyram use scenarios with 35-day and 7.37-day foliar dissipation half-lives using upper-bound Kenaga values 
                                        
                          Watermelons and Strawberries
                            max exposure scenario[a]
                                   Cherries 
                            min exposure scenario[b]
                                    Potatoes
                scenario with highest number of applications[c]
                                  Forage Type
                                        
                                35-day half-life
                               7.37-day half-life
                                35-day half-life
                               7.37-day half-life
                                35-day half-life
                               7.37-day half-life
                                  short grass
                                      2.17
                                      1.85
                                      0.90
                                      0.77
                                      1.29
                                      0.95
                                   tall grass
                                      1.00
                                      0.85
                                      0.41
                                      0.35
                                      0.59
                                      0.44
                       broadleaf plants and small insects
                                      1.22
                                      1.04
                                      0.51
                                      0.43
                                      0.73
                                      0.54
                           fruits/pods/large insects
                                      0.14
                                      0.12
                                      0.06
                                      0.05
                                      0.08
                                      0.06
 [a]  The maximum application rate for watermelons and strawberries is 0.222 lbs a.i./A, with a 5-day application interval and 2 applications.
 [b] The maximum application rate for cherries is 0.092 lbs a.i./A, with a 5-day application interval and 2 applications. This scenario for cherries results in the lowest EECs from any of proposed application rates for any crop on the Fluopyram 500 SC label. All scenarios for terrestrial modeling use the maximum application rate for any given use pattern. Therefore, these numbers represent the exposure from the maximum application rate for the crop with the lowest proposed use rates of fluopyram. 
 [c] The maximum aerial application rate for potatoes is 0.092 lbs a.i./A, with 5-day application interval and 3 applications. The aerial scenario for potatoes has the highest number of applications for any crop on the Fluopyram 500 SC label.
 Bolded values represent LOC exceedances (RQ >=1).
 
 
 Table 27.  Chronic mammalian dietary RQs estimated for fluopyram use scenarios with 35-day and 7.37-day foliar dissipation half-lives using upper-bound Kenaga values
                                        
                          Watermelons and Strawberries
                            max exposure scenario[a]
                                   Cherries 
                            min exposure scenario[b]
                                    Potatoes
                scenario with highest number of applications[c]
                                  Forage Type
                                        
                                35-day half-life
                               7.37-day half-life
                                35-day half-life
                               7.37-day half-life
                                35-day half-life
                               7.37-day half-life
                                  short grass
                                      7.81
                                      6.66
                                      3.24
                                      2.76
                                      4.63
                                      3.42
                                   tall grass
                                      3.58
                                      3.05
                                      1.48
                                      1.26
                                      2.12
                                      1.57
                       broadleaf plants and small insects
                                      4.39
                                      3.75
                                      1.82
                                      1.55
                                      2.60
                                      1.93
                           fruits/pods/large insects
                                      0.49
                                      0.42
                                      0.20
                                      0.17
                                      0.29
                                      0.21
 a  The maximum application rate for watermelons and strawberries is 0.222 lbs a.i./A, with a 5-day application interval and 2 applications.
 [b] The maximum application rate for cherries is 0.092 lbs a.i./A, with a 5-day application interval and 2 applications. This scenario for cherries results in the lowest EECs from any of proposed application rates for any crop on the Fluopyram 500 SC label. All scenarios for terrestrial modeling use the maximum application rate for any given use pattern. Therefore, these numbers represent the exposure from the maximum application rate for the crop with the lowest proposed use rates of fluopyram. 
 [c] The maximum aerial application rate for potatoes is 0.092 lbs a.i./A, with 5-day application interval and 3 applications. The aerial scenario for potatoes has the highest number of applications for any crop on the Fluopyram 500 SC label.
 Bolded values represent LOC exceedances (RQ >=1).
 
 
 		a.  Location of Wildlife Species 	
 
 For screening terrestrial risk assessments, a generic bird or mammal is assumed to occupy either the treated field or adjacent areas receiving the pesticide at a rate equivalent with the treatment rate on the target field.  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.  
 
 		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. The assumption of 100% diet from a treated area may be realistic for acute exposures, but long-term exposures modeled as single food types composed entirely of material from a treated field is uncertain. 
 
 Inhalation Exposure
 The screening risk assessment also considered acute inhalation exposure from spray material in droplet form at the time of application and vapor phase pesticide volatilizing from treated surfaces. Inputs for the STIR tool (version 1.0) included fluopyram's molecular weight (396.72 g/mole), vapor pressure (2.33 x 10[-8] mm Hg), maximum application rate (0.222 lbs a.i./acre), as well as available avian and mammalian toxicity information. Because no definitive endpoints were available for acute oral mammalian or avian studies, the highest concentration tested was used as an upper-bound estimate of acute toxicity (2000 mg a.i./kg bw for both mammals and birds). A 4-hour rat inhalation study was submitted for fluopyram (LC50 = 2.091 mg a.i./L). Due to the chemical's low vapor pressure, low acute oral toxicity to mammals and birds and low inhalation toxicity to mammals, acute inhalation exposure at the time of fluopyram application is not an appreciable route of exposure for mammals or birds. 
 
 Dermal Exposure
 The screening assessment does not consider fluopyram dermal exposure to terrestrial organisms. 
 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. Fluopyram's solubility in water (16 mg/L) and toxicity to avian and mammalian species are inputs for the potential upper-bound drinking water calculations. Because no definitive endpoints were available for acute oral mammalian or avian studies, the highest concentration tested was used as an upper-bound estimate of acute toxicity (2000 mg a.i./kg bw for both mammals and birds). Chronic NOAEL/NOAEC toxicity values were 15 mg a.i./kg bw for mammals and 46.7 mg a.i./kg diet for birds. Based on this information, fluopyram exposure through drinking water alone does not present an acute concern for mammals or birds or chronic concern for mammals. There is a potential chronic concern from drinking water exposure for birds.			
 	
       	c.  Incidental Pesticide Releases Associated with Use 	
 
 This risk assessment is based on the assumption that the entire treatment area is subject to fluopyram application at the rates specified on the label.  In reality, there is the potential for uneven application of fluopyram 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.  Residue Levels Selection 
 			
 As discussed earlier in the exposure section of this document, the Agency relies on the work of Kenaga and Fletcher et al. (1994) for setting the assumed pesticide residues in wildlife dietary items. The Agency believes that these residue assumptions reflect a realistic upper-bound residue estimate for pesticides, with the assumption that these residues reflect a chemical-specific estimate for fluopyram.  
 
 
       4.  Effects Assessment 
 
 

 The data available to support the terrestrial and aquatic effects assessment for fluopyram is incomplete.  Data gaps, uncertainties and limitations are summarized as follows:
 
   * Non-definitive acute avian endpoints:  Risk quotients were not calculated for acute risk to birds based on the non-definitive endpoints in the submitted acute and dietary studies (LD50 > 2000 mg ai/kg bw; LC50 > 4785 mg ai/kg bw). However, mortality and sublethal effects were noted at the lowest concentrations tested. The lowest treatment level at which observations of mortality and sublethal effects occurred (mortality occurred in 1/10 birds; 500 mg ai/kg bw) is approximately 4 to 71 times higher than the peak upper bound EECs of the highest fluopyram use scenario (0.41  -  116 mg ai/kg bw), depending on the dietary item and using the smallest size of the bird (most conservative) in the terrestrial exposure modeling. Some uncertainty exists in defining the lowest level at which mortality or sublethal effects would occur, since a NOAEC was not established in the most sensitive acute oral and dietary studies. All submitted acute oral and dietary studies with birds were determined to be acceptable and meet US EPA guideline requirements, with the exception of the limit test conduct with a passerine species (zebra finch, supplemental). Because overall acute risk to avian species appears to be low, an additional passerine study is not requested at this time.

   * Chronic effects to estuarine/marine fish and estuarine/marine invertebrates:  No chronic data were submitted for estuarine/marine fish or estuarine/marine invertebrates. An acute-to-chronic ratio could not be calculated due to lack of available data on definitive acute toxicity endpoints for any aquatic taxa. The expected chronic exposure of fluopyram to aquatic organisms is low (60-day EEC = 0.286 ug a.i./L). The level-of-concern for chronic risk to aquatic organisms was not exceeded for freshwater fish or freshwater aquatic invertebrates (LOC >1.0; freshwater fish chronic RQ = 0.001, Table 17; freshwater invertebrate chronic RQ = 0.0006, Table 18). On an acute basis, both freshwater and estuarine/marine fish showed low sensitivity to fluopyram exposure (LC50 > 0.98 mg a.i./L and NOAEC = 0.98 mg a.i./L for sheepshead minnow; LC50 >1.78 mg a.i./L and NOAEC = 1.78 mg a.i./L for rainbow trout; Table 15). Freshwater and estuarine/marine invertebrates also showed low sensitivity on an acute basis (EC50 > 17 mg a.i./L and NOAEC = 17 mg a.i./L for Daphnia magna; EC50 >0.51 mg a.i./L and NOAEC = 0.98 mg a.i./L for saltwater mysid; Table 15). In addition, the maximum chronic predicted exposure concentration in the water column is approximately four orders of magnitude less than the available chronic estuarine/marine benthic invertebrate toxicity endpoint (NOAEC) based on pore water concentrations. Based on these lines of evidence, chronic testing with estuarine/marine fish or estuarine/marine invertebrates is not requested at this time.

   * Differences in TGAI vs. TEP:  In this risk assessment, ecological effects studies with the fluopyram technical grade active ingredient were compared to predicted exposure concentrations based on movement of the chemical via runoff/erosion and spray drift. However, in EFED risk assessments, toxicity endpoints from studies with water column dwelling animals and the typical end use product (TEP) are used quantitatively to estimate risk resulting from exposure to spray drift only. Formulated products containing fluopyram are expected to be directly deposited to aquatic systems via spray drift. Therefore, to provide a realistic representation of the expected effects and risk to aquatic animals associated with spray drift, toxicity endpoints based on concentrations of the active ingredient in laboratory studies with the formulated product are compared to estimated exposure concentrations from expected concentrations of the active ingredient to aquatic environments via drift only. Because the spray drift is only a fraction of the total aquatic EECs, and the TEP does not show greatly enhanced toxicity compared to the TGAI (see Table 15), the risk quotients calculated with the spray drift + runoff/erosion EECs and fluopyram technical toxicity endpoints are expected to be a more conservative estimate of risk than estimates with spray drift only and fluopyram TEP toxicity endpoints. However, the solubility of the TEP may be greater than that of the TGAI, which can result in increased bioavailability in the environment (see discussion of solubility in aquatic tests below).

   * Solubility in aquatic tests:  According to the submitted fate information, fluopyram is characterized by a water solubility ranging from 15 to 16 mg a.i./L in acidic to alkaline conditions. However, acute fish studies with technical-grade fluopyram were conducted up to the limits of solubility determined under the specific test conditions, which ranged from 1 to 6 mg a.i./L. In the TEP toxicity study, treatment levels were up to fluopyram concentrations of 46.4 mg ai/L for freshwater fish. In the submitted acute study for mysid, a solvent was used without adverse impacts on the solvent control test organisms (0.1 mL/L DMF). However, the solubility of the test material was also low in this study, as fluopyram levels were only tested up to 0.51 mg ai/L. In acute studies with Daphnia magna, studies were conducted up to the limit of solubility that was determined to be 17 mg a.i./L for the technical product and 38.2 for the formulated fluopyram 500 SC, under the specific test conditions. One submitted aquatic study with the formulated product noted the presence of undissolved test material (highest three treatment levels that were nominally 8.72 to 49.8 mg ai/L, acute test with rainbow trout, MRID 473723333). In another test with the technical product, the presence of undissolved test material was observed at all treatment levels (nominal concentrations of 11.8 to 189 mg ai/L, acute test with carp, MRID 47372332). No undissolved test material was noted in any other submitted studies with the formulated or technical product. It is unclear why the solubility of fluopyram technical would be much lower in the test conditions of some of the aquatic toxicity tests. 

The higher solubility of the formulated product in some toxicity studies indicates that the solubility of fluopyram in the environment may be higher than the concentrations of active ingredient that were tested. However, the TEP showed low solubility in a study with rainbow trout. The maximum potential for exposure to aquatic ecosystems, utilizing the value for water solubility (16 mg a.i./L) reported in the available fate information, is much lower than any of the levels at which effects were observed in the submitted aquatic organism toxicity tests (see Risk Characterization section). 

   * Terrestrial plant toxicity studies: No acceptable Tier II study is available for buckwheat, which showed a 50% reduction in biomass in the acceptable Tier I study. The submitted Tier II study did not allow reliable calculation of an EC25 or NOAEC.

   * Fluopyram co-formulations:  Based on the toxicity data submitted for the fluopyram coformulations with tebuconazole and trifloxystrobin, these products are more toxic to aquatic organisms than fluopyram only. This increase in toxicity appears to be attributable to the presence of the non-fluopyram active ingredients, which are more toxic to aquatic taxa. Although no data were submitted for the coformulated products, both pyrimethanil and prothioconazole are more toxic to aquatic organisms than fluopyram, with the potential exception of pyrimethanil effects to freshwater fish. Therefore, it appears as if use of the fluopyram co-formulated products with tebuconazole, trifloxystrobin, pyrimethanil, and prothioconazole have a higher potential to adversely impact aquatic ecosystems than use of the proposed fluopyram-only product. Overall, the coformulations for all fluopyram products with dual active ingredients appear to have low acute toxicity to terrestrial organisms, but no avian data were submitted for any co-formulated product. However, only rat acute oral studies were submitted for pyrimethanil and prothioconazole coformulations. Although these studies indicate that the products show low acute toxicity to mammals, there is uncertainty regarding the effects of these products on other terrestrial taxa.

All four fungicides in the coformulation have different modes-of-action than fluopyram (FRAC, 2009). Fluopyram is a succinate dehydrogenase inhibitor that alters cellular respiration. Tebuconazole and prothioconazole are demethylation inhibitors that affect sterol biosynthesis in membranes. Trifloxystrobin is the most similar to fluopyram, as quinine outside inhibitor that also affects respiration. Pyrimethanil is an aniline-pyrimidine that impacts amino acid and protein synthesis. This indicates that these chemicals should act independently within an exposed organism, with the potential exception of trifloxystrobin.
 
 
 		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.
 
 		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 fluopyram than the surrogates, risks may be under- or overestimated, respectively. The Agency is not limited to a base set of surrogate toxicity information in establishing risk assessment conclusions. The Agency also considers toxicity data on non-standard test species when available. Further research is needed to determine whether, in general, reptiles and terrestrial-phase amphibians are suitably represented by bird species in assessing risks for fluopyram and fish are an appropriate surrogate for aquatic-phase amphibians.   	
 					
 		
 		c.  Use of the Most Sensitive Species Tested 
 
 Although the screening 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. 	Literature Cited
 
Environmental Fate Studies 

47372247
Bogdoll, B.; Eyrich, U. (2005) Water Solubility of AE C656948 at pH 4, pH 7, pH 9 and in Distilled Water (Flask Method). Project Number: PA05/074. Unpublished study prepared by Bayer Cropscience Gmbh. 22 p.
47372249
Smeykal, H. (2008) 1st Amendment to Report No. 20050612.01: AE C656948; Substance, Pure: AE C656948 00 1B99 0001: Vapour Pressure A.4. (OECD 104). Project Number: 20050612/01. Unpublished study prepared by Siemens Axiva GmbH & Co. KG. 19 p.
47372245
Eyrich, U.; Bogdoll, B. (2006) Partition Coefficients 1-Octanol / Water of AE C656948 (Shake Flask Method). Project Number: PA06/065. Unpublished study prepared by Bayer Cropscience Gmbh. 22 p.
47372248
Bogdoll, B.; Lemke, G. (2006) Solubility in Organic Solvents: AE C656948: Pure Substance. Project Number: PA05/113. Unpublished study prepared by Bayer Cropscience Gmbh. 21 p.
47372303
Doble, M.; Oddy, A. (2006) [Carbon 14]-AE C656948: Aqueous Hydrolysis at pH 4, 7 and 9. Project Number: CX/06/015, M/282473/01/2. Unpublished study prepared by Battelle UK, Ltd. 69 p.
47372304
Oddy, A.; Brett, R. (2008) [Carbon 14]-AE C656948: Aqueous Photolysis in Buffer at pH 7. Project Number: CX/06/016, M/297180/02/2. Unpublished study prepared by Battelle UK, Ltd. 121 p.
47372305
Stupp, H.; Koehn, D. (2007) [Phenyl-UL-(Carbon 14)]AE C656948 and [Pyridyl-2-6-(Carbon 14)]AE C656948: Phototransformation in Natural Water. Project Number: M1121681/0, MEF/07/227, M/296408/01/2. Unpublished study prepared by Bayer CropScience AG. 81 p.
47372306
Doble, M.; Oddy, A. (2007) [Carbon 14]-AE C656948: Soil Photolysis. Project Number: CX/06/022, M286872/01/3. Unpublished study prepared by Battelle UK, Ltd. 82 p.
47372307
Babczinski, P. (2008) [Phenyl-UL-(Carbon 14)]AE C656948: Aerobic Soil Metabolism/Degradation and Time-Dependent Sorption in Four Soils. Project Number: MEF/06/295, BCP/133, M1311501/2. Unpublished study prepared by Bayer CropScience AG. 145 p.
47372308
Menke, U.; Telscher, M. (2008) [Pyridine-2,6-(Carbon 14)] AE C656948: Aerobic Metabolism/Degradation and Time-Dependent Sorption in Soils. Project Number: M165/1679/1, MEF/07/424, M298413/01/2. Unpublished study prepared by Bayer CropScience AG. 148 p.
47372309
Meyer, B. (2008) [Phenyl-UL-(Carbon 14)] and [Pyridyl-2-6-(Carbon 14)]AE C656948: Aerobic Soil Metabolism in Two US Soils. Project Number: MEGMP069/1, M/299548/02/1. Unpublished study prepared by Bayer CropScience. 91 p.
47372310
Meyer, B. (2008) [Phenyl-UL-(Carbon 14)] and [Pyridyl-2-6-(Carbon 14)]AE C656948: Anaerobic Soil Metabolism . Project Number: MEGMP070/1, M292022/02/1. Unpublished study prepared by Bayer CropScience. 82 p.
47372311
Allan, J.; Shepherd, J. (2007) [Pyridyl-Ring-UL-(Carbon 14)]-AE C656948 and [Triflurobenzamide-Ring-UL-(Carbon 14)]-AE C656948: Aerobic Aquatic Metabolism. Project Number: MEGMP064, M/290531/01/2. Unpublished study prepared by Bayer CropScience. 109 p.
47372312
Dallstream, K.; Mislankar, S.; Desmarteau, D. (2007) [(Carbon 14)-Phenyl-UL]AE C656948: Anaerobic Aquatic Metabolism. Project Number: MEGMP063, M/293275/01/2. Unpublished study prepared by Bayer CropScience. 68 p.
47372313
Dallstream, K.; Mislankar, S.; Desmarteau, D. (2007) [Pyridyl-2,6-(Carbon 14)]AE C656948: Anaerobic Aquatic Metabolism. Project Number: MEGMP063, M293276/01/2. Unpublished study prepared by Bayer CropScience. 68 p.
47372301
Henk, F.; Haas, M. (2005) AE C656948: Adsorption/Desorption on Five Soils. Project Number: MEF/04/499, M1311423/5, MO/05/006241. Unpublished study prepared by Bayer CropScience AG. 84 p.
47372302
Heinemann, O.; Dehner, D. (2007) [Pyridine-2,6-(Carbon 14)] AE C656948-7-Hydroxy: Adsorption/Desorption on Four EU Soils. Project Number: MEF/07/149, M1311630/5, M289570/01/2. Unpublished study prepared by Bayer CropScience. 79 p.
47567001
Xu, T. (2008) Terrestrial Field Dissipation of AE C656948 in a Washington Soil, 2006. Project Number: MEGMP065, M/306817/01/2, 01023. Unpublished study prepared by Bayer CropScience, Agvise Laboratories. and Qualls Ag Laboratory. 235 p.
47567002
Xu, T. (2008) Terrestrial Field Dissipation of AE C656948 in a New York Soil, 2006. Project Number: MEGMP084, M/306809/01/2, P601060020. Unpublished study prepared by Bayer CropScience, Agvise Laboratories and Agricultural Chemistry Development Services, Inc. (ACDS). 238 p.
47567003
Xu, T. (2008) Terrestrial Field Dissipation of AE C656948 in a North Dakota Soil, 2006. Project Number: M/306812/01/2, MEGMP085, 01023. Unpublished study prepared by Bayer CropScience, Agvise Laboratories and Agvise Research. 237 p.
47567004
Xu, T. (2008) Terrestrial Field Dissipation of AE C656948 in a Georgia Soil, 2006. Project Number: MEGMP086, M/306814/01/2, 01023. Unpublished study prepared by Bayer CropScience, Agvise Laboratories and Ag Research Associates. 234 p.
47567005
Lembrich, D.; Rapp, V.; Neumann, B.; et al. (2008) Terrestrial Field Dissipation of AE C656948 in California Soil, 2006. Project Number: MEGMP087, M/306820/01/2. Unpublished study prepared by Agvise Laboratories, California Agricultural Research Inc. and Bayer CropScience. 150 p.
47372337
Bruns, E.; Weber, E. (2008) [Pyridyl-2,6-(Carbon 14)]- Fluopyram Bioconcentration and Biotransformation in Fish (Lepomis macrochirus). Project Number: EBGMP116, E/244/3300/6, M/298506/01/2. Unpublished study prepared by Bayer CropScience AG. 251 p.
EU study No MRID
Heinemann, O.; Telscher, M. (2007) Determination of the Residues of AE C656948 in/on Soil after Spraying of AE C656948 (250 SC) in the Field in Germany, United Kingdom, Sweden, France, Spain and Italy
EU study No MRID
Heinemann, O.; Telscher, M. (2007) Interim Report: Determination of the Residues of AE C656948 in/on Soil after Spraying of AE C656948 (250 SC) in Germany and France
 
 
 B.  Ecological Effects Studies Submitted to EPA 
MRID
Author(s)
Year
Title 
47372349
Bach, F.; Nguyen, D. H.
2008
AE C656948 SC 500A G effect on seedling emergence and seedling growth test of ten species of non-target terrestrial plants (Tier 1 and 2)
SE07/037 BCS  

47372350
Bach, F.; Nguyen, D. H.
2008
AE C656948 SC 500A G - Effect on the vegetative vigour of ten species of non-target terrestrial plants (Tier 1)
VV07/038 BCS  

47372403
Banman, C. S.; Lam, C. V.
2007
Toxicity of AE C656948 technical to the green alga Pseudokirchneriella subcapitata
EBGMP048 BCS  
 
47372406
Banman, C. S.; Lam, C. V.
2007
Toxicity of AE C656948 technical to the  freshwater diatom Navicula pelliculosa
EBGMP040 BCS  
 
47372404
Banman, C. S.; Lam, C. V.
2007
Toxicity of AE C656948 technical to the blue-green algae Anabaena flos-aquae
EBGMP049 BCS  
 
47372330
Banman, C. S.; Lam, C. V.
2006
Acute toxicity of AE C656948 technical to the sheepshead minnow (Cyprinodon variegatus) under static conditions
EBGMP053 BCS  
 
47372405
Banman, C. S.; Lam, C. V.
2007
Toxicity of AE C656948 technical to the saltwater diatom Skeletonema costatum
EBGMP050 BCS  
 
47372341
Barfknecht, R.
2008
Acute oral toxicity for bobwhite quail (Colinus virginianus) with AE C656948 technical
BAR/LD 074 BCS  
 
47372343
Barfknecht, R.
2007
AE C656948 technical 5-day-dietary LC50 for bobwhite quail (Colinus virginianus)
BAR/LC 023 BCS  
 
47372342
Barfknecht, R.
2007
AE C656948 technical 5-day-dietary LC50 mallard duck (Anas platyrhynchos)
BAR/LC 020 BCS  
 
47372324
Bruns, E.
2007
Acute toxicity of AE C656948 (tech.) to the waterflea Daphnia magna in a static laboratory test system
EBGMP046 BCS  
 
47372334
Bruns, E.
2008
Influence of AE C656948 (tech.) on development and reproductive output of the waterflea Daphnia magna in a static renewal laboratory test system
EBGMP047 BCS  
 
47372325
Bruns, E.
2008
Acute toxicity of AE C656948 SC 500A G to the waterflea Daphnia magna in a static laboratory test system
EBGMP067 BCS  
GLP: Y, published: N
1783598 / 
47372337
Bruns, E.;  Weber, E.
2008
[pyridyl-2,6-14C]- fluopyram bioconcentration and biotransformation in fish (Lepomis macrochirus)
EBGMP116 BCS  
 
47372346
Christ, M.T.; Lam, C. V.
2008
Effect of AE C656948 technical on reproduction of the mallard duck (Anas platyrhynchos)
EBGMP041 BCS  
 
47567008
Desmarteau, D.; Sabbagh,G.
2008
Foliar half-life calculation for AE C656948 in grass forage and hay
EBGMP158 BCS  
 
47372418
Dorgerloh, M.
2008
Pseudokirchneriella subcapitata growth inhibition test with fluopyram-lactame
EBGMP155 BCS  
 
47372340
Dorgerloh, M.
2008
Chironomus riparius 28-day chronic toxicity test with fluopyram (tech.) in a water-sediment system using spiked water
EBGMP121 BCS  
 
47372401
Dorgerloh, M.
2007
Lemna gibba G3 - Growth inhibition test with AE C656948 under static conditions
EBGMP051 BCS  
 
47372333
Dorgerloh, M.
2008
Acute toxicity of fluopyram SC 500 G to fish (Oncorhynchus mykiss) under static conditions
EBGMP066 BCS  
 
47372407
Dorgerloh, M.
2008
Pseudokirchneriella subcapitata growth inhibition test with fluopyram SC 500
EBGMP068 BCS  
 
47372402
Dorgerloh, M.
2008
Lemna gibba G3 growth inhibition test with fluopyram SC 500A G under static conditions
EBGMP151 BCS  
 
47372432
Eiben, R.
2005
AE C656948 SC 500 - Acute toxicity in the rat after dermal application
AT02500 BCS  
47372435
Folkerts, Andree
2007
AE C656948 SC 500 - Acute inhalation toxicity in rats
AT03663 BCS
47372434
Folkerts, Andree
2006
AE C656948 SC 500 - Acute inhalation toxicity in rats
AT03464 BCS
47372344
Frey, L. T.; Martin, K. H.; Beavers, J. B.; Jaber, M.
2008
AE C656948: A reproduction study with the Northern bobwhite
EBGMP152 BCS  
 
47372426

Frommholz, U.
2007
AE C656948 SC 500A G: Influence on the reproduction of the collembola species Folsomia candida tested in artificial soil with 5 % peat
FRM-COLL-50/07 BCS  

47372409
Heimbach, F.
2008
AE C656948 SC 500: Effects on survival, growth and reproduction on the earthworm Eisenia fetida tested in artifical soil with 5 percent peat
LKC-RG-R-20/06 BCS  

47372418
Hills, M.
2008
Evaluation of the pre-emergence (PPI) biological activity of AE C656948 SC 500
PPI-07002 BCS  

47372441
Kennel, P.
2005
AE C656948 90-day toxicity study in the rat by dietary administration
SA04048 BCS  
47372425
Kratz, M. A.
2007
Fluopyram SC 500: Influence on mortality and reproduction on the soil mite species Hypoaspis aculeifer tested in artificial soil with 5 % peat
KRA-HR-3/07 BCS  

47372408
Lechelt-Kunze, C.
2005
AE C656948: Acute toxicity  to earthworms (Eisenia fetida) tested in artificial soil with 5 percent peat
LKC/RG-A-57/05 BCS  
 
47372410
Leicher, T.
2006
AE C656948 SC 500: acute toxicity to earthworms (Eisenia fetida) tested in artificial soil with 5 percent peat
LRT/RG-A-78/06 BCS  
 
47372331
Matlock, D.; Lam, C. V.
2008
Acute toxicity of AE C656948 technical to the fathead minnow (Pimephales promelas) under static conditions
EBGMP237 BCS  
 
47372328
Nieden, D.
2008
Acute toxicity of AE C656948 (tech.) to fish (Oncorhynchus mykiss) under static conditions
EBGMP017 BCS  
 
47372329
Nieden, D.
2008
Acute toxicity of AE C656948 (tech.) to fish (Lepomis  macrochirus) under static conditions
EBGMP052 BCS  
 
47372332
Nieden, D.
2008
Acute toxicity of AE C656948 (tech.) to fish (Cyprinus carpio) under static conditions
EBGMP020 BCS  
 
47372336
Nieden, D.
2007
Early-life stage toxicity of AE C656948 (tech.) to fish Pimephales promelas)
EBGMP054 BCS  
 
47372327
                                       
Palmer, S. J.; Kendall, T. Z.; Krueger, H. O.
2007
AE C656948: A 96-hour flow-through acute toxicity test with the saltwater mysid (Americamysis bahia)
EBGMP043 BCS  
 
47372326
Palmer, S. J.; Sutherland, C. A.; Kendall, T. Z.; Krueger, H. O.
2006
AE C656948: A 96-hour shell deposition test with the eastern oyster (Crassostrea virginica)
EBGMP045 BCS  
 
47372338
Putt, A. E.
2008
AEC656948 - Toxicity to marine amphipods (Leptocheirus plumulosus) during a 10-day sediment exposure
EBGMP119 BCS  
 
47372339
Putt, A. E.
2008
AEC656948 - Life-cycle toxicity test exposing midges (Chironomus tentans) to a test substance applied to sediment under static-renewal conditions following EPA test methods
EBGMP128 BCS  
 
47372335
Putt, A. E.
2008
AEC656948 - Toxicity to estuarine amphipods (Leptocheirus plumulosus) during a 28-day sediment exposure
EBGMP153 BCS  
 
47372427
Roehlig, U.
2007
Dose-response toxicity (LR50) of AE C656948 SC 500 to the parasitic wasp Aphidius rhopalosiphi   under laboratory conditions
06 10 48 187 BCS  

47372428

Roehlig, U.
2007
Dose-response toxicity (LR50) of AE C656948 SC 500  to the predatory mite Typhlodromus pyri under laboratory conditions
06 10 48 188 BCS  

47372424
Roehlig, U.
2007
Chronic dose-response toxicity (ER50) of AE C656948 SC 500 to the rove beetle Aleochara bilineata under extended laboratory conditions
07 10 48 018 A BCS  

47372347
Schmitzer, S.
2007
Effects of AE C656948 (acute contact and oral) on honey bees (Apis mellifera L.) in the laboratory
24851035 BCS  

47372348
Schmitzer, S.
2008
Effects of AE C656948 SC 500A G (acute contact and oral) on honey bees (Apis mellifera L.) in the laboratory
34481035 BCS  

47372430
Schuengel, M.
2008
AE C656948 SC 500 - Acute toxicity in the rat after oral administration
AT03603 BCS  
 
47567007
Stafford, J. M.
2008
AE C656948 - Acute oral toxicity test (LD50) with the zebra finch (Taeniopygia guttata) following OECD draft guideline 223
EBGMP117-1 BCS  
 
47372345
Stoughton, T. L.; Lam, C. V.
2008
Effect of AE C656948 technical on reproduction of the northern bobwhite quail
EBGMP004-1 BCS  
 
 
 
 C.  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.
 
 Carsel, R. F., J. C. Imhoff, P. R. Humel, J. M. Cheplick, and A. S. Donigian, Jr. 1997. PRZM-3, A Model for Predicting Pesticide and Nitrogen Fate in the Crop Root and Unsaturated Zones: User's Manual for Release 3.0. National Exposure Research Laboratory, Office of Research and Development, U. S. Environmental Protection Agency, Athens, GA.
 
Di Toro, D.M., C. Zarba, D.J. Hansen, W. Berry, R.C.Swartz, C.E. Cowan, S.P. Pavlou, and H.E. Allen.
1991. Technical basis for establishing sediment quality criteria for nonionic organic chemicals using
equilibrium partitioning. Environ. Toxicol.Chem. 10:1541-1583.
 
 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. And Chem. 13(9):1383-1391.
 
 Fungicide Resistance Action Committee. FRAC code list:  Fungicides sorted by mode of action. 2009. http://www.frac.info/frac/publication/anhang/FRAC_CODE_LIST.pdf   
 
 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.
 
 Terrestrial Residue Exposure Model (T-REX), Version 1.4.1.  October 2008.  Environmental Fate and Effects Division, Office of Pesticide Programs, U.S. Environmental Protection Agency, Washington, D.C.
 
 US EPA. 1993. Wildlife Exposure Factors Handbook. Volume I of II.  EPA/600/R-93/187a. Office of Research and Development, Washington, D. C. 20460.
 
 US EPA. 1996. Ecological Effects Test Guidelines, 850.2100 Avian Acute Oral Toxicity Test. Office of Chemical Safety and Pollution Prevention. EPA 712-C-96-139.
 
 US EPA. 2002. Technical Basis for the Derivation of Equilibrium Partitioning Sediment Guidelines (ESGs) for the Protection of Benthic Organisms:  Nonionic Organics. Office of Science and Technology and Office of Research and Development. Washington, DC 20460. EPA/822-R-02-041.
 
 US EPA. 2004a. 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.
 
 USEPA. 2004b.  Scientific Advisory Panel.  March 30 - April 2, 2004: Refined (Level II) Terrestrial and Aquatic Models for Probabilistic and Ecological Assessment of Pesticides.  Available: http://www.epa.gov/scipoly/sap/meetings/2004/033004_mtg.htm
 
 USEPA, 2005. Procedures for the Derivation of Equilibrium Partitioning Sediment Benchmarks (ESBs) for the Protection of Benthic Organisms:  Metal Mixtures (Cadmium, Copper, Lead, Nickel, Silver and Zinc). Office of Research and Development. Washington, DC 20460. EPA/600/R-02/011.
 
USEPA 2009.  Evaluation of Potential Ecological Risks from the Proposed New Use of Tebuconazole on Fruiting Vegetables (Crop Group 8). DP Barcode:  DP362764. Office of Chemical Safety and Pollution Prevention. Washington, DC. November 13, 2009.

USEPA 2010a. Ecological risk assessment for the new use of Trifloxystrobin [Trifloxystrobin Flowable Fungicide, EPA Reg. No. 264-989] on alfalfa seed. DP Barcode:  D378918. Office of Chemical Safety and Pollution Prevention. Washington, DC. December 17, 2010.

US EPA 2010b. Environmental Fate and Ecological Risk Assessment for New Uses of Prothioconazole, DP Barcodes:  D378999, 373681, 378623, 381890. Office of Chemical Safety and Pollution Prevention. Washington, DC. December, 2010
 
USEPA 2011a. Drinking water and ecological risk for an increase of maximum use rate of tebuconazole on golf course turf. DP Barcode(s): 389256, 389288, 386328. Office of Chemical Safety and Pollution Prevention. Washington, DC. July 28, 2011.

USEPA 2011b. Ecological Risk Assessment for Use of Fluopyram/Trifloxystrobin 500 SC on Almonds, Apples, Cherries, Cucurbit Vegetables, Peanuts, Pecans, Pistachios, Potatoes, Sugar Beets, Stone Fruits, Tree Nuts, and Wine Grapes. DP Barcode(s): D385876, D387594. Office of Chemical Safety and Pollution Prevention. Washington, DC. June 13, 2011.

USEPA 2011c. Prothioconazole:  Evaluation of Proposed New Fungicide Products Containing Prothioconazole and Fluopyram. DP Barcode:  D385873. Office of Chemical Safety and Pollution Prevention. Washington, DC. May 17, 2011.

USEPA 2011d.  Section 3 New Use: Ecological Risk Assessment for the proposed use of pyrimethanil (co-formulated with fluopyram) on almond, apple, pistachio, potato, stone fruit (except cherries), and wine grapes. DP Barcode:  D387590. Office of Chemical Safety and Pollution Prevention. Washington, DC. July 26, 2011.

US Office of the Federal Registrar. 2011. Code of Federal Regulations 40, Parts 150-189. 
 
 Willis and McDowell, 1987. Pesticide persistence on foliage. Environ. Contam. Toxicol.  100:23-73.