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

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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
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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
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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 TERRPLANT models

D. List of Ecological Effects Data

E. The Risk Quotient Method and Levels of Concern

F. Detailed Risk Quotients

G. Data Requirements
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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
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 fluopyramonly 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
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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.

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

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.
4

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

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.

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

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 nonvascular 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. 

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Table 2. Summary of Environmental Risk Conclusions for Terrestrial Organisms Exposed to Fluopyram

Risk Conclusion Summarized Risk Characterization and Major Uncertainties
5

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.

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

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.
6

Table 2. Summary of Environmental Risk Conclusions for Terrestrial Organisms Exposed to Fluopyram

Risk Conclusion Summarized Risk Characterization and Major Uncertainties

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.

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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.

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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-ofconcern 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.

----------------------------------------------------------------------------------------------------------
7

Table 2. Summary of Environmental Risk Conclusions for Terrestrial Organisms Exposed to Fluopyram

Risk Conclusion Summarized Risk Characterization and Major Uncertainties

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 μg 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.
8

C. Conclusions - Exposure Characterization 

Fluopyram has low vapor pressure/Henry’s Law constant (2.33x10-8torr/2.94 x 10-10 atm m3

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 (90th % t1⁄2 ranges from 1,360 

to 1,757 days); relatively stable to aqueous photolysis (t1⁄2= 57 days), and persistence under 

aerobic soil conditions (90th percentile t1⁄2= 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 
9

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. 

II. 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, 
10

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 10-8torr and Henry’s Law constant= 2.94 x 10-10 atm m3 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 

(90th percentile t1⁄2= 464 days in aerobic systems and stable in anaerobic systems) and in 

aerobic/anaerobic water/sediment systems (extrapolated t1⁄2 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. 
11

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) 
12

Table 3. Taxonomic groups and test species evaluated for ecological effects in this screening-level risk 

assessment.

Taxonomic group Representative species

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
13

Table 4. Toxicity endpoints used in risk quotient calculations 

Taxonomic group Representative species

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 
14

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 
15

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.
16

Figure 1a The aquatic conceptual model for spray application of fluopyram to agricultural crops

(dotted lines indicate unlikely routes of chemical dissipation).
17

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 
18

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-in10 year EECs. More information on these models can be found at 

http://www.epa.gov/oppefed1/models/water/index.htm.
19

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 firstorder 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 halflife (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 
20

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, organlevel 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 
21

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.
22

III. 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
23

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

FLU+PTZ 0.150 2 0.300 7 Ground, Air

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

1Premixed Formulations: Fluopyram alone= FLU SOLO; With Tebuconazole= FLU+TEB; With Trifloxystrobin= FLU+TFS; With 

Pyrimethanil= FLU+PYM; and With Prothioconazole= FLU+PTZ.

2Number 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
24

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 10-8torr 

and Henry’s Law constant= 2.94 x 10-10 atm m3 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 3ppm

In toluene 62.20 x 10 3ppm

In dichloromethane, methanol, acetone, ethyl acetate, 

and di-methyl sulfoxide > 250 x 10 3ppm

Water

MRID 47372247

Solvents

MRID 4732248

Vapor pressure

20°C → 9.00 x 10-9torr; 1.2 x 10-6Pa; 1.18 x 10-11atm

25°C → 2.33 x 10-8torr; 3.1 x 10-6Pa; 3.06 x 10-11atm

50°C → 2.18 x 10-6torr; 2.9 x 10-4Pa; 2.86 x 10-9 atm MRID 47372249

Henry’s Law 

Constant (@ pH 7 

& 20 ̊C) 2.94 x 10-10 atm m3 mole-1 Calculated from VP at 25°C

Kow 2,060 (Log Kow = 3.314) MRID 47372245
25

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 

14

C-labelled active substance 

uniformly labelled in one of the two rings: the phenyl and the pyridyl rings (Figure 3).

N

H

O

N

Cl CF3

CF3

*

* denotes position of radiolabel, uniformly labelled in 

the phenyl ring

N

H

O

N

Cl CF3

CF3

* *

* denotes position of radiolabel, labelled in the 2- and 

6-position of the pyridyl ring

[phenyl-UL14C] 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-UL14C] and the [pyrrdyl-2,6 14C] 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 (t1⁄2= 57 days; MRID 473723-07) and was practically stable by photolysis on soil 

surfaces subjected to sunlight (t1⁄2= 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
26

Property Description or Value Reference*

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 (1st

value for Pyridyl 

label and the 2nd

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-methylsulfoxide (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
27

Property Description or Value Reference*

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, Fluopyrambenzamide and Fluopyram-PCA with maximum concentrations of 9.8 μg/kg 

(equivalent to 19% of 0-day parent) and 10.2 μg/kg (16%), respectively, at 6 

DAT

Minor Degradation products: one minor transformation product, Fluopyram7-hydroxy with a maximum concentration of 3.0 μg/kg (3% of 0-day parent 

equivalent) were observed at the CA site

475670-01

475670-02

475670-03

475670-04

and

475670-05
28

Property Description or Value Reference*

Fish 

Bioconcentration

(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-OHGA (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).
29

CF3 O

N

H

N

CF Cl 3

CF3 O

NH2

HO

N

CF Cl 3

O

HO

N

CF S 3

O

O

H3C

CF3 O

N

H

N

CF Cl 3

OH

Figure 4 Environmental degradation pathways for fluopyram 

 Fluopyram Parent

N

CF3

HN

O

F3C

 Molecular Cleavage

 

Lactam 7-Hydroxy

 Cleavage

Benzamide PCA

Methyl Sulfoxide

Very Limited aerobic soil degradation (Parent hydroxylation) limited aqueous photolysis
30

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
31

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-

14C] 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 (9x10-9torr) 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 biotransformation 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 
32

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 1st

lb a.i./A Kg a.i./ha Application (DD/MM)**

(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
33

Crop Scenario*

Single Application Rate

Number of 

Applications

Date of 1st

lb a.i./A Kg a.i./ha Application (DD/MM)**

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
34

Crop Scenario*

Single Application Rate

Number of 

Applications

Date of 1st

lb a.i./A Kg a.i./ha Application (DD/MM)**

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

CAStrawberrynoplasticRLF_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. 
35

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-m

3 mol-1 @ 20 oC) 2.94E-10

Solubility in Water(mg/L) 16

Photolysis in Water (t1⁄2 in days @ pH 7) 57

Aerobic Soil Metabolism (90th % t1⁄2 in days for 6 soils x two labels) 464

Hydrolysis (t1⁄2 in days @ pH 7) Stable

Aerobic Aquatic Metabolism (90th % t1⁄2 in days whole system t1⁄2 in days

for two systems x two labels) 1,360

Anaerobic Aquatic Metabolism (90th % t1⁄2 in days whole system t1⁄2 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 

Application intervals Table 2, above)

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 μg 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
36

Crop Scenario Peak 21-day 60-day

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
37

Crop Scenario Peak 21-day 60-day

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 
38

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. 
39

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)
40

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 (semiaquatic areas) lbs a.i./A for ground application and from 0.011 (spray drift) to 0.055 (semiaquatic 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
41

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
42

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)

TEP

41.5%

Rainbow Trout

Oncorhynchus 

mykiss

96 hours LC50 >46.4 mg 

a.i./Lb

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 μg a.i./L

LOAEC = 

2996 μg a.i./L

Offspring production was affected 

at the highest treatment level, 

2996 μg 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 μg a.i./L.

MRID 47372334

(Acceptable)

Estuarine/Marine Fish
43

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)

Acute TGAI

94.7%

Sheepshead minnow

Cyprinodon 

variegatus

96 hours LC50 >0.98 mg 

a.i./La

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
44

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)

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 

14C-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
45

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)

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. Meanmeasured 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)

Fluopyramlactame 

(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)
46

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)

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 
47

mortality or sublethal effects were observed at the solubility limit (1.78 mg a.i./L, meanmeasured) 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. 
48

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 μg/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 
49

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). 
50

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 fluopyramspiked 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 
51

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
52

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

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 postmortem findings were observed.

MRID 

47372343

Acceptable 
53

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

Chronic TGAI

(94.7% a.i.)

Bobwhite 

quail

(Colinus 

Virginianus) 

and Mallard 

duck (Anas 

platyrhyncho

s)

Avian 

reproduction 

study 

(dietary 

exposure, 

one 

generation) 

NOAEC = 46.7 mg 

a.i./kg dieta

LOAEC = 75.7 mg 

a.i./kg dieta

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 μg 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 μg a.i./bee

Oral toxicity

LC50 > 89 μg a.i./bee

Contact toxicity

1/50 mortality in the 83.2 μg a.i./bee

level and no mortality in the control 

(5 reps of 10 bees). 

Oral toxicity

1/50 mortality in the 89 μg 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
54

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

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
55

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

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, 
56

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. 
57

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 
58

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
59

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 coformulated product appear to have low overall toxicity to terrestrial organisms. However, no 

avian data was submitted.
60

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 coformulated 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 coformulations. 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.
61

IV. 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 
62

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

(μg a.i./L)

NOAEC

(μg a.i./L)

EECc

Peak

(μg a.i./L)

EECd

60-Day

(μg a.i./L)

Acute

RQ

(EEC/LC50)

Chronic

RQ

(EEC/NOAEC)

Freshwater fisha> 1780 269 7.31 0.286 Not 

calculated 0.001

Estuarine/marine 

fishb > 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

(μg a.i./L)

NOAEC

(μg a.i./L)

EECc

Peak

(μg a.i./L)

EECc

21-Day

(μg a.i./L)

Acute

RQ

(peak 

EEC/LC50)

Chronic

RQ

(21-day 

EEC/NOAEC)
63

Table 18. Acute and chronic risk quotients (RQs) for evaluating toxic risk of fluopyram exposure to 

freshwater and estuarine/marine aquatic invertebrates. 

Organism

LC50

(μg a.i./L)

NOAEC

(μg a.i./L)

EECc

Peak

(μg a.i./L)

EECc

21-Day

(μg a.i./L)

Acute

RQ

(peak 

EEC/LC50)

Chronic

RQ

(21-day 

EEC/NOAEC)

Freshwater 

invertebratesa > 17,000 1214 7.31 0.712 Not calculated 0.0006

Estuarine/marine 

invertebratesb > 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 μg 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 μg a.i./kg 

OC; > 2500 μg 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

(μg a.i./kg 

OC)

LC50

(μg a.i./L 

pore water)

Peak 

Sediment 

EEC c, d, e

(μg a.i./ kg 

OC)

Peak Pore 

Water EEC

(μg a.i./L pore 

water) c

Acute 

sediment

RQ

(peak 

EEC/LC50)

Acute 

pore water

RQ

(peak EEC/ 

LC50)
64

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

(μg a.i./kg 

OC)

LC50

(μg a.i./L 

pore water)

Peak 

Sediment 

EEC c, d, e

(μg a.i./ kg 

OC)

Peak Pore 

Water EEC

(μg a.i./L pore 

water) c

Acute 

sediment

RQ

(peak 

EEC/LC50)

Acute 

pore water

RQ

(peak EEC/ 

LC50)

Freshwater 

invertebratesa

Not 

available

Not 

available 63.8 0.142 Not calculated Not calculated

Estuarine/marine 

invertebratesb > 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 μg /kg dry weight sediment = 63.8 μg 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 μg /kg dry weight sediment = 2,700,000 μg 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

(μg a.i./kg 

OC)

NOAEC

(μg a.i./L 

pore water)

21-day 

Sediment 

EEC c, d, f

(μg a.i./ kg 

OC)

21-day Pore 

Water EEC

(μg a.i./L pore 

water) c

Chronic

sediment

RQ

(21-day EEC/

NOAEC)

Chronic

pore water

RQ

(21-day 

EEC/NOAEC)

Freshwater 

invertebratesa 1,180,000 3800 12.2 0.027 0.00001 0.000007

Estuarine/marine 

invertebratesb 643,000 2500 12.2 0.027 0.00002 0.00001
65

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

(μg a.i./kg 

OC)

NOAEC

(μg a.i./L 

pore water)

21-day 

Sediment 

EEC c, d, f

(μg a.i./ kg 

OC)

21-day Pore 

Water EEC

(μg a.i./L pore 

water) c

Chronic

sediment

RQ

(21-day EEC/

NOAEC)

Chronic

pore water

RQ

(21-day 

EEC/NOAEC)

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 μg /kg dry weight sediment = 12.2 μg 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 μg /kg dry weight sediment = 1,180,000 μg 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 μg /kg dry weight sediment = 643,000 μg 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 a3400 1170 7.31 0.00215 0.006

Vascular plants b2600 278 7.31 0.00281 0.026
66

Table 21. Acute RQs for non-vascular and vascular aquatic plants exposed to fluopyram. 

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. Dietarybased 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 
67

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 halflife 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). 
68

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 TREX 

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 
69

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 μg 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 μg 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 μg 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 
70

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 μg 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 μg 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 μg 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.
71

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-ofconcern (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 (t1⁄2= 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. 
72

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 

μg a.i./kg OC; > 2500 μg 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 μg 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 
73

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 dosebased 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 dietarybased 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).
74

Acute Risk to Mammals

Results of oral toxicity study conducted on rats show that fluopyram TGAI is practically nontoxic 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 dosebased 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. 
75

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 μg 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 soildwelling 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 
76

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 
77

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 
78

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 
79

uniform mixing does not account for stratification due to thermoclines (e.g., seasonal 

stratification in deep water bodies). Additionally, the dimensions of the standard runoff 

scenario assume a watershed area to water body volume ratio of 10 ha: 20,000m3. This 

ratio is recommended to maintain a sustainable constructed pond in the Southeastern 

United States. The use of higher watershed area to water body volume ratios (as 

recommended for sustainable ponds in drier regions of the United States) may lead to 

higher pesticide concentrations when compared to the standard watershed area to water 

body volume ratio.

• The standard runoff scenario assumes uniform soils and agronomic management 

practices across the standard 10 hectare field. Soils can vary substantially across even 

small areas; this variation is not reflected in the model simulations. Additionally, the 

impact of unique soil characteristics and soil management practices (e.g., tile drainage) 

are not considered in the standard runoff scenario. The assumption of uniform site and 

management conditions is not expected to represent some site-specific conditions. 

Extrapolating the risk conclusions from the standard pond scenario to other aquatic 

habitats (e.g., marshes, streams, creeks, and shallow rivers, intermittent aquatic areas) 

may either underestimate or overestimate the potential risks in those habitats.

• For an acute risk assessment, there is 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 timeto-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). 
80

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 postapplication, 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 90th 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 90th 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 
81

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 scenarioa

Cherries 

min exposure 

scenariob

Potatoes

scenario with highest 

number of 

applicationsc

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.
82

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 scenarioa

Cherries 

min exposure 

scenariob

Potatoes

scenario with highest 

number of 

applicationsc

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 scenarioa

Cherries 

min exposure 

scenariob

Potatoes

scenario with highest 

number of 

applicationsc

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
83

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. 
84

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:
85

 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 acuteto-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 μg 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 
86

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).
87

 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 coformulated 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 anilinepyrimidine 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 
88

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. 
89

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 

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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.
90

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.

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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

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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

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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.
91

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 
92

MRID Author(s) Year Title 

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 
93

MRID Author(s) Year Title 

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 
94

MRID Author(s) Year Title 

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 
95

MRID Author(s) Year Title 

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 
96

MRID Author(s) Year Title 

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 

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