MRID 47372327
 (Acceptable)
                                                                        Chronic
                                    Data Gap
 Freshwater Benthic Invertebrates
                                                                          Acute
                                    Data Gap
                                                                        Chronic
                                      TGAI
                                     94.7%

 Midge
 Chironomus tentans
                                    54 days
 Sediment concentrations
 NOAEC = 26 mg a.i./kg sediment
 LOAEC = 48 mg a.i./kg sediment

 Pore water concentrations
 NOAEC = 3.8 mg a.i./L pore water
 LOAEC = 8.8 mg a.i./L pore water
 The most sensitive endpoints were larval survival (assessed on day 20) and percent emergence. These endpoints were statistically-reduced at the 48 and 96 mg TRR/kg sediment levels.  Midge growth (assessed on day 20) and development rate for both sexes were statistically-reduced at the 96 mg TRR/kg sediment level.
 MRID 47372339
 (Supplemental)
 Estuarine/Marine Benthic Invertebrates
                                                                          Acute
                                      TGAI
                                     94.7%
 Saltwater amphipod
 Leptocheirus plumulosus
                                    10 days
 Sediment value:
 LC50 > 100 mg a.i./kg sediment
 NOAEC=100 mg a.i./kg sediment

 Pore water value:
 LC50 > 7.5 mg a.i./L pore water
 NOAEC = 7.5 mg a.i./L pore water

 Mortality was 1, 5, 6, 3 and 2% in the 5.8, 14, 26, 51 and 100 mg [14]C-AEC656948 equivalents/kg dry sediment treatment groups, respectively.

 No sublethal effects observed.
 MRID 47372338
 (Acceptable)
                                                                        Chronic
                                      TGAI
                                     94.7%
 Saltwater amphipod
 Leptocheirus plumulosus
                                    28 days
 Sediment concentrations
 NOAEC = 36 mg TRR/kg sediment
 LOAEC = 92 mg TRR/kg sediment

 Pore water concentrations
 NOAEC = 2.5 mg TRR/L pore water
 LOAEC = 5.9 mg TRR/L pore water
 The reviewer's analysis detected a significant difference between the negative and solvent control groups for this endpoint, with significantly fewer (25%) offspring produced in the solvent control group. The dose-response for reproduction was poor.
 MRID 47372335
 (Supplemental)
 Aquatic Plants
                                                                    Algae Acute

                                      TGAI
                                     94.7%
 Pseudokirchneriella subcapitata
                                    96 hours
 EC50 = 4.3 mg a.i./L
 NOAEC = 1.46 mg a.i./L
 (biomass)
 Biomass was the most sensitive endpoint. Compared to the control, the percent inhibition ranged from 10-99% for cell density, 9-99% for biomass and 2-95% for growth rate. Mean-measured concentrations were <0.005 (<LOQ; controls), 0.093, 0.241, 0.584, 1.46, 3.78, and 9.53 mg a.i./L.
 No cell abnormalities were reported.
                                 MRID 47372403
                                  (Acceptable)

                                      TEP
                                     41.5%
 Pseudokirchneriella subcapitata
                                    72 hours
 EC50 = 3.4 mg a.i./L
 NOAEC = 1.17 mg a.i./L
 (cell density)
 Cell density was the most sensitive endpoint. Compared to the control, the percent inhibition ranged from -18-99% for cell density and -3.4-110% for growth rate. Mean-measured concentrations were <0.002 (<LOQ; controls), 0.379, 1.17, 3.84, 12.5, and 38.65 mg a.i./L.
 No cell abnormalities were reported.
                                 MRID 47372407
                                  (Acceptable)

                         Fluopyram-lactame (metabolite)
                                      94%
 Pseudokirchneriella subcapitata
                                    72 hours
 EC50 >8.87 mg a.i./L
 NOAEC = 8.87 mg a.i./L
 (for both cell density and growth rate)
 No treatment-related effects were observed at the highest level tested for either cell density or growth rate.
                                 MRID 47372418
                                  (Acceptable)
                                   Macrophyte
                                     Acute
                                      TGAI
                                     94.7%
 Duckweed
 Lemna gibba
                                     7 days
 EC50 = 2.6 mg a.i./L
 NOAEC = 0.28 mg a.i./L
 (frond number based on yield)
Frond number based on yield was the most sensitive endpoint. There were no phytotoxic effects in the first three treatment levels.  Small fronds and slight chlorosis were observed in the 4.04 mg a.i./L test concentration, while single fronds and slight to medium chlorosis were observed in the highest test concentration (8.88 mg a.i./L).
 Based on frond number, the percent inhibition in the treated samples as compared to the negative control ranged from 1.2 to 92.9%.  Based on frond area, the percent inhibition in the treated samples as compared to the negative control ranged from -3.8 to 90%.
                                 MRID 47372401
                                  (Acceptable)

                                      TEP
                                     41.6%
 Duckweed
 Lemna gibba
                                     7 days
 EC50 = 2.9 mg a.i./L
 NOAEC = 1.04 mg a.i./L
 (frond number based on yield)
The most sensitive endpoint was frond number based on yield. There were no phytotoxic effects in the first two treatment levels.  Small fronds, medium necrosis, and slight chlorosis were observed in the 4.34 mg a.i./L test concentration.  Single fronds, small fronds, and medium necrosis were observed in the 8.42 mg a.i./L treatment level.  Small fronds, medium necrosis, single fronds, and strong necrosis were observed in the highest test concentration (15.9 mg a.i./L).
 Based on frond number, the percent inhibition in the treated samples as compared to the negative control ranged from 3.9 to 94.5%.  Based on frond area, the percent inhibition in the treated samples as compared to the negative control ranged from 9.7 to 92.2%.
                                 MRID 47372402
                                  (Acceptable)

 [a] These values were used for evaluation of risk via spray drift only.

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

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

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

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

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

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

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

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

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

 No studies were submitted to examine fluopyram chronic effects on estuarine/marine fish.

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

No studies were submitted to examine fluopyram chronic effects on estuarine/marine invertebrates in the water column.

A short-term 10-day study was submitted for sediment-dwelling estuarine/marine invertebrates. No treatment-related effect on survival of the marine amphipod Leptocheirus plumulosus was observed.  The data for the marine amphipod Leptocheirus plumulosus suggest that fluopyram is practically non-toxic to benthic saltwater invertebrates, as no treatment-related effect on survival were observed (LC50 >100 mg TRR/kg dw sediment and > 7.5 mg TRR/L pore water).

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

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

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

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

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

Two aquatic vascular plant studies were submitted for fluopyram, one study with the technical product and another with the formulated product (Fluopyram SC 500A). In a 7-day acute toxicity study, the freshwater macrophyte, duckweed (Lemna gibba), was exposed to fluopyram technical. The most sensitive endpoint was frond number based on yield, with NOAEC and EC50 values of 0.278 and 2.6 mg a.i./L, respectively. There were no phytotoxic effects in the first three treatment levels.  Small fronds and slight chlorosis were observed in the second highest treatment level (4.04 mg a.i./L), while single fronds and slight to medium chlorosis were observed in the highest test concentration (8.88 mg a.i./L). In another 7-day acute toxicity study, freshwater duckweed (Lemna gibba), was exposed to the formulated fluopyram product. Small fronds, necrosis and chlorosis were observed at the three highest treatment levels (4.34, 8.42, and 15.9 mg a.i./L). The most sensitive endpoint was frond number based on yield, with NOAEC and EC50 values of 1.04 and 2.9 mg a.i./L, respectively.

 	2.  Terrestrial Effects

 The acute and chronic toxicity references values associated with fluopyram exposure to terrestrial animals are summarized in Table 16.

 Table 16.  Toxicity reference values for terrestrial organisms exposed to fluopyram technical or formulated fluopyram (Fluopyram SC 500A, 41.5% active ingredient).
                               Exposure Scenario
                              % Active Ingredient
                                    Species
                               Exposure Duration
                                   Toxicity
                                Reference Value
                                     Effect
                                   Reference
 Mammals
                                                                          Acute
TGAI
(94.7% a.i.)

 Laboratory Rat
 (Rattus norvegicus)
 Single oral dose
 LD50 > 2000 mg a.i./kg bw
 No mortalities observed at 2000 mg/kg. No effects on weight or other gross pathological findings were reported.
 MRID
 47372430

 Acceptable
                                                                       Chronic
TGAI
 (94.7% a.i.)

 Laboratory Rat (Rattus norvegicus)
 90-day dietary study
 NOAEL = 13 mg a.i./kg bw/day

 LOAEL = 61 mg a.i./kg bw/day
Decreased body weight and food consumption observed at the two highest treatment levels (61 and 204 mg a.i./kg/day for male rats, 70 and 230 mg a.i./kg day for female rats).

 MRID 47372441

 Acceptable
 Birds
                                                                          Acute
TGAI
 (94.5% a.i. [bobwhite]  and 94.7% a.i [zebra finch]).
 Northern bobwhite quail (Colinus virginianus) and zebra finch (Taeniopygia guttata)
 Single oral dose
 LD50 >2000 mg a.i./kg bw

 Bobwhite quail:  Cumulative mortality was 0/9, 1/10, 1/10, and 4/10 birds from the control, 500, 1000, and 2000 mg ai/kg bw nominal treatment levels, respectively.
 Treatment-related signs of toxicity were observed at all dose levels, including diarrhea, soft excrement, ptosis, fluffed feathers, red excrements, and reduced vigilance. Necropsy of birds that died during the study indicated severe emaciation, reduction in organ size (breast muscle, liver, spleen, heart, and/or liver) and discoloration of organs (gizzard, intestines, and/or pancreas). Therefore, the NOAEL <500 mg a.i./kg bw.

 Zebra finch:  Two limit tests were conducted with the zebra finch. Six birds were exposed in each individual test. In the first test, one mortality occurred. A second test was conducted and no mortalities occurred. Pilorection, ataxia, lethargy, wing droop and uncoordination were observed in the single treatment level. Therefore, the NOAEL is <2000 mg a.i./kg bw.
 MRIDs 47372341
 Acceptable

 and

 47567007
 Supplemental

                                                                          Acute
TGAI
 (95.0% a.i.)
 Northern bobwhite quail (Colinus virginianus)
 5-Day dietary
 LC50 >4785 mg a.i./kg diet

 Based upon treatment-related reductions (24 to 64% of control) in food consumption at all treatment levels on day 7, the reviewer determined the NOAEC to be <279 mg ai/kg diet.  There was a statistically-significant reduction in body weight in birds from the 4785 mg ai/kg diet level during the exposure period.  No mortality, clinical signs of toxicity, or post-mortem findings were observed.
 MRID 47372343

 Acceptable
                                                                        Chronic
TGAI
 (94.7% a.i.)
 Bobwhite quail
 (Colinus Virginianus) and Mallard duck (Anas platyrhynchos)
 Avian reproduction study (dietary exposure, one generation)
 NOAEC = 46.7 mg a.i./kg diet[a]

 LOAEC = 75.7 mg a.i./kg diet[a]
 The NOAEC value is based on a treatment-related reduction in 14-day survivor body weight for bobwhite quail chicks (mean-measured concentrations) (MRID 47372344).  In this study, reductions in hatchling body weight and percentage of 14-day survivors/number of hatchlings were also observed at 175 mg a.i./kg diet. Other studies showed additional reproductive effects such as reductions in adult female body weight gain, reduced number of eggs laid, increased numbers of cracked or defective eggs, increased embryonic mortality, reductions in egg shell strength & thickness, and reductions in the number of hatchlings and 14-day chick survivors at higher treatment levels.
 MRIDs 47372344
 Acceptable

 47372345
 Supplemental

 47372346
 Acceptable
 Terrestrial Insects
                                                                          Acute
TGAI
 (95.5% a.i.)
 Honey bee
 (Apis mellifera)

 96-Hour acute contact and oral toxicity test

 Contact toxicity
 LD50 >100 μg test material/bee

 Oral toxicity
 LC50 >102.3 ug test material/bee
 No mortalities or sublethal effects were observed in the controls or treatment groups for either test.
 MRID 47372347

 Contact toxicity test:
 Acceptable

 Note:  No guideline available for acute oral toxicity to honey bees.

                                                                          Acute
TEP
 (41.6% a.i.)
 Honey bee
 (Apis mellifera)

 96-Hour acute contact and oral toxicity test

 Contact toxicity
 LD50 > 83.2 ug a.i./bee

 Oral toxicity
 LC50 > 89 μg a.i./bee

 Contact toxicity
 1/50 mortality in the 83.2 ug a.i./bee level and no mortality in the control (5 reps of 10 bees).

 Oral toxicity
 1/50 mortality in the 89 ug a.i./bee level and no mortality in the control (5 reps of 10 bees).

 No sublethal effects were observed in the controls or treatment groups for either test.
 MRID 47372348

 Contact toxicity test:
 Acceptable

 Note:  No guideline available for acute oral toxicity to honey bees.
 Plants - Tier I seedling emergence
                                                                        Monocot
TEP
 (41% a.i.)
 Oat (Avena sativa), perennial ryegrass (Lolium perenne),  barley (Hordeum vulgare) and corn (Zea mays)
 Single application at test initiation
 EC25 >0.444 lbs a.i./A
 NOAEC = 0.444 lbs a.i./A
 No detrimental effects >=25% were observed for any test species.

 The highest reduction in seedling emergence for monocots was 6.3% in barley (not statistically significant) at the 0.444 lb a.i./A treatment level. The highest reduction in dry weight for monocots was 9.9% in ryegrass (not statistically significant) at the 0.444 lb a.i./A treatment level.
 MRID 47372349

 Acceptable
                                                                          Dicot
TEP
  (41% a.i.)
 Sugarbeet  (Beta vulgaris),  oilseed rape (Brassica napus),  soybean (Glycine max),  cucumber  (Cucumis sativus),  buckwheat  (Fagopyrum esculentum)  and sunflower (Helianthus annuus)
 Single application at test initiation
 EC25 <0.444 lbs a.i./A
 NOAEC <0.444 lbs a.i./A
 Buckwheat was the most sensitive dicot species. A significant reduction (50.4%) was observed in buckwheat dry weight at the 0.444 lbs a.i./A treatment level.

 Mild inhibition in height occurred across treatments, with soybean having the highest level of inhibition of 12.1% in comparison to the control (statistically significant) at the 0.444 lbs a.i./A treatment level. Soybeans also had a statistically significant reduction in dry weight, 14.1% in comparison to the control.
 MRID 47372349

 Acceptable
 Plants - Tier II seedling emergence
                                                                          Dicot
TEP
(41% a.i.)
 Buckwheat
 (Fagopyrum esculentum)
 Single application at test initiation
 No acceptable endpoints available
 The most sensitive endpoint was biomass. No clear dose-dependent pattern for effects on biomass was observed due to high variance. Compared to the negative control, reductions in biomass were 12.3, 1.6, 21.3, 40.1 and 6.2% at nominal concentrations of 0.028, 0.056, 0.111, 0.222, and 0.444 lbs a.i./acre respectively.

 Inhibition in height was very mild across all test concentrations. No other phytotoxic effects were reported.
 MRID 47372349

 Supplemental
 Plants - Tier I vegetative vigor
                                                                        Monocot
TEP
 (41% a.i.)
 Onion (Allium cepa), oat (Avena sativa), perennial ryegrass (Lolium perenne) and corn (Zea mays)
 Single application at test initiation
 EC25 >0.222 lbs a.i./A
 NOAEC = 0.222 lbs a.i./A
 There were no detrimental effects >=25% for any test species and no species or endpoint exhibited a significant reduction in survival, dry weight or height compared to the controls. Corn showed the highest reduction in dry weight in comparison to the control (6.1%) at 0.222 lbs a.i./A, but this difference was not statistically significant.

 Inhibition in height was very mild across all treatments, with no species exhibiting inhibitions of 5% in comparison to the negative control.
 MRID 47372350

 Acceptable
                                                                          Dicot
TEP
 (41% a.i.)
 sugarbeet (Beta vulgaris), oilseed rape (Brassica napus), cucumber (Cucumis sativus), buckwheat (Fagopyrum esculentum), soybean (Glycine max) and sunflower (Helianthus annuus)
 Single application at test initiation
 EC25 >0.222 lbs a.i./A
 NOAEC = 0.222 lbs a.i./A
 For dry weight, sugarbeet had the highest level of inhibition of 20.2% in comparison to the negative control. However, a t-test was not able to detect a significant difference between this treatment group and the control.
 Inhibition in height was very mild across all treatments, with no species exhibiting inhibitions of 5% in comparison to the negative control.
 MRID
 47372350

 Acceptable

 Mammals
 For terrestrial mammals, one acute oral toxicity study, one acute dermal study and two acute inhalation studies were conducted with laboratory rats exposed to fluopyram TGAI (MRIDs 47372430, 47372432, 47372434 and 47372435). Several subchronic and chronic mammalian studies with fluopyram TGAI were submitted, including a 90-day dietary rat study, a 1-year dietary canine study, a chronic feeding/carcinogenicity rat study and a 2-generation reproduction rat study (MRIDs 47372441, 47372449, 47372501 and 47372447). A subchronic dietary rat study was also submitted for fluopyram-PCA (MRID 47372521). No additional information was submitted for the formulated product fluopyram 500 SC (see Appendix D for full mammalian toxicology profile).

 Results of oral, dermal and inhalation toxicity studies on rats show that fluopyram TGAI is practically non-toxic to mammals on an acute basis. The acute 4-hour LC50 was determined to be greater than 2.091 mg/L and 5.1 mg/L in the two rat inhalation studies submitted for fluopyram, which indicates low toxicity via inhalation exposure. No mortality was observed in any of the studies, but sublethal effects observed in the inhalation study included slow and labored breathing, piloerection, ungroomed hair-coat, reduced motility, high-legged gait and limpness. The LD50 is greater than 2000 mg a.i./kg bw for both oral and dermal exposure routes. There were no effects on body weight gain in any of the acute studies. Based on the non-definitive endpoints available from these toxicity studies risk quotients will not be calculated.  However, predicted exposures will be compared to the highest concentrations tested to qualitatively assess risk to these species.

 Chronic and reproductive studies with rats and dogs indicate that fluopyram TGAI can affect both parents and offspring at levels as low as 61 mg/kg/day. Toxicity was observed at similar levels in a chronic 1-year dietary study with dogs and a 2-generation reproduction study with rats. In the chronic dog study, decreased weight and food consumption occurred at the 66 mg/kg bw/day treatment level (NOAEL=13 mg/kg bw/day). In a 90-day rat dietary study with fluopyram, decreased body weight and food consumption were observed at 61 mg/kg bw/day (NOAEL=13 mg/kg/day).Effects observed in the 2-generation rat reproduction study included decreased body weight in the offspring (NOAEL = 15 mg/kg bw/day; LOAEL = 83 mg/kg bw/day). To assess chronic risk to mammals, EFED will use the NOAEL of 13 mg a.i./kg bw/day based on reductions in body weight and food consumption in the submitted 90-day rat dietary study.

In a chronic dietary carcinogenicity study with mice, effects were observed at lower levels of exposure than the dietary and 2-generation studies with rats. The NOAEL for systemic toxicity = 4 mg/kg/day and the LOAEL for systemic toxicity = 21 mg/kg/day, based on treatment-related follicular cell hyperplasia in the thyroid gland, centrilobular to panlobular hypertrophy and hepatocellular single cell degeneration /necrosis in the liver. Because these parameters are not clearly linked to the typical ecological endpoints of survival, growth and reproduction, these endpoints were not selected for risk estimation.

 Fluopyram-PCA, a metabolite of fluopyram, showed much lower toxicity than the parent compound based on a single 28-day dietary rat toxicity study. In the subchronic study with fluopyram-PCA, no treatment-related effects were observed at the highest level tested (NOAEL=1574 mg/kg/day). In similary subchronic 28-day rat and mouse dietary studies conducted with the parent compound fluopyram, treatment-related effects including decreased body weight gain and increased liver weight were observed at levels as low as 162 mg/kg/day (MRIDs 47372516 and 47372517).

 Birds
 All toxicity reference values used to assess the potential acute and chronic risks of fluopyram exposure to birds were obtained from studies using fluopyram TGAI.

 The results of a two oral toxicity studies with fluopyram indicate that the chemical is practically nontoxic to avian species on an acute basis, based on mortality effects. The incidence of mortalities did not occur at a level high enough to establish an LD50 in either study (bobwhite quail LD50  > 2000 mg a.i./kg bw, MRID 47372341; zebra finch LD50 > 2000 mg a.i./kg bw, MRID 47567007). In the study conducted with bobwhite quail, mortality occurred at all treatment levels (4 out of 10 test birds died at the highest treatment level [2000 mg ai/kg bw level], while 1 out of 10 birds died in the other two lower treatments [500 mg a.i./kg bw and 1000 mg a.i./kg bw]). Slight to severe treatment-related effects on food consumption were observed at all dose levels. Body weight losses were observed in test birds at the 2000 mg ai/kg bw level. Two limit tests were conducted with the zebra finch. Six birds were exposed in each individual test. In the first test, one mortality occurred. A second test was conducted and no mortalities occurred. Pilorection, ataxia, lethargy, wing droop and uncoordination were observed in the single treatment level. Therefore, the NOAEL is <2000 mg a.i./kg bw.

 Because the low mortality (<50%) in submitted acute avian tests, which did not allow determination of an LD50, acute risk quotients will not be calculated. Nonetheless, the observed mortality and sublethal effects of fluopyram and comparison to expected environmental exposure concentrations will be discussed in the risk characterization section of this document.

 Two submitted 5-day dietary toxicity studies are available for fluopyram. In a study with mallard duck, there were no treatment-related effects on mortality, clinical signs of toxicity, body weight, or food consumption to the tested species, mallard duck. The acute dietary LC50 was >4604 mg ai/kg diet. Based upon a notable increase in the incidences of red pancreases in surviving birds at the 4604 mg ai/kg diet level, the NOAEC was 2307 mg ai/kg diet. The acute dietary toxicity fluopyram technical to 9-day old northern bobwhite quail was also assessed. The acute dietary LC50 was >4785 mg ai/kg diet.  Based upon treatment-related reductions (24 to 64% of control) in food consumption at all treatment levels on day 7, the reviewer determined the NOAEC to be <279 mg ai/kg diet. Furthermore, there was a statistically-significant reduction in body weight in birds from the 4785 mg ai/kg diet level during the exposure period.  No mortality, additional clinical signs of toxicity, or post-mortem findings were observed. Because these studies resulted in a non-definitive LC50 endpoint, risk quotients will not be calculated. However, predicted exposures will be compared to the levels at which mortality and sublethal effects were observed to qualitatively assess dietary risk to these species.

 Results of avian reproduction studies show that there is concern for exposure to fluopyram TGAI with effects seen in both parents and hatchlings. The NOAEC value for birds is 46.7 mg a.i./kg diet based on a treatment-related reduction in 14-day survivor body weight for bobwhite quail chicks in a one-generation reproductive toxicity test, with corresponding LOAEC of 75.7 mg a.i./kg diet (based on mean-measured concentrations) (MRID 47372344).  In this study, reductions in hatchling body weight and percentage of 14-day survivors/number of hatchlings were also observed at 175 mg a.i./kg diet. Other studies showed additional reproductive effects such as reductions in adult female body weight gain, reduced number of eggs laid, increased numbers of cracked or defective eggs, increased embryonic mortality, reductions in egg shell strength & thickness, and reductions in the number of hatchlings and 14-day chick survivors at higher treatment levels (MRIDs 47372345 and 47372346). To assess chronic risk to birds, the chronic NOAEC of 46.7 mg a.i./kg diet (MRID 47372344) will be used to calculate risk quotients.

 Terrestrial Invertebrates
 Results of acute contact toxicity studies with honey bees demonstrate that fluopyram TGAI is practically non-toxic to beneficial insects.  Two acute oral toxicity tests conducted with fluopyram showed the TGAI having an LD50 > 97.7 μg a.i./bee (102.3 μg test material/bee) and formulated fluopyram having an LD50 > 89 μg a.i./bee. The acute contact tests showed an LC50 > 95.5 μg a.i./bee (100 μg test material/bee) for the TGAI and an LC50 > 83.2 μg a.i./bee for the fluopyram formulation. No definitive endpoints were given in any of the acute toxicity tests with honeybees, due to lack of mortality.

 Additional studies with fluopyram technical and the end-use product (Fluopyram SC 500, 41.8% active ingredient) were submitted for other nontarget terrestrial invertebrates, including predatory mite (Typhlodromus pyri), rove beetle (Aleochara bilineata, springtail (Folsomia candida), soil mite (Hypoaspis aculeifer) and earthworm (Eisenia fetida). None of these studies resulted in an LC50 or EC50, as 50% mortality did not occur at the highest treatment level in any of the tests (LC50s ranged from >20.31 mg a.i./kg dw soil to >1000 mg a.i./kg dw soil for earthworms; LD50 > 801.8 mL a.i./ha for rove beetles; LC50 >415 mg a.i./kg dw soil for soil mites and springtails; LC50 >825.9 mL a.i./ha for parasitic wasp; LC50 >834.2 mL a.i./ha for predatory mite).  The highest single application rate of 0.222 lbs a.i./acre (6.84 fl oz product/acre) is equivalent to 207 mL a.i./ha.

In two 14-day toxicity studies, statistically significant weight loss (10-23%) was observed in earthworms exposed to fluopyram at treatment levels >131 mg a.i./kg dw of soil. No adverse effects on mortality or growth were observed in a 28-day subchronic study with earthworms exposed to lower levels of the end-use product (1.85 to 20.31 mg a.i./kg dw soil), but a reduced number of surviving juveniles occurred at the highest treatment levels (8-23% reduction compared to the control, NOAEC = 3.27 mg a.i./kg dw soil). In the 28-day reproduction test conducted with the springtail, the test organisms were exposed to nominal application rates of 26.1 to 415 mg a.i./kg dw soil. After 28 days, significant mortality occurred (29.5-45.5%) and the number of juveniles was significantly reduced (36.5-36.9%) at the two highest treatment levels (207.5 and 415 mg a.i./kg dw soil).

 The Agency does not currently assess quantitative risk to non-target terrestrial invertebrates. However, these toxicity data will be used for a qualitative evaluation in the risk characterization section.

 Terrestrial Plants
 For terrestrial plants, Tier I seedling emergence and vegetative vigor toxicity tests showed no detrimental effects >=25% in survival, dry weight or height compared to the controls for any test species except buckwheat in the seedling emergence test (MRIDs 47372349 and 47372350).

 In the vegetative vigor study, sugarbeet had the highest level of inhibition in dry weight, a 20.2% reduction in comparison to the negative control at a fluopyram application rate of 0.222 lbs a.i./A. Because this is a Tier I study and a 25% or greater adverse effect did not occur, a Tier II study is not requested. However, a t-test was not able to detect a significant difference between this treatment group and the control.

 The rate applied in the Tier I seedling emergence test, 0.444 lbs a.i./A, was greater than the maximum application rate of 0.222 lbs a.i./A. Because buckwheat showed a 50.4% reduction in dry weight at 0.444 lbs a.i./A in the seedling emergence test, a Tier II test was conducted (MRID 47372349). The most sensitive endpoint was biomass. No clear dose-dependent pattern for effects on biomass was observed due to high variance. Compared to the negative control, reductions in biomass were 12.3, 1.6, 21.3, 40.1 and 6.2% at nominal concentrations of 0.028, 0.056, 0.111, 0.222, and 0.444 lbs a.i./acre respectively.

A non-guideline terrestrial plant study that evaluated the pre-plant incorporated biological effects of fluopyram 500 SC was also submitted. There were no effects on plant emergence across species, except for oat and ryegrass, which experienced effects at the first two treatment levels.  Due to promotion of growth at the highest treatment level, a dose-response relationship cannot be inferred. There was no additional crop damage in any species, and there was no effect of the treatment on fresh weight across all species (EC25 >0.44 lbs a.i./A, NOAEC = 0.44 lbs a.i./A).

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

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

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

Only limited toxicity data were available for the fluopyram/pyrimethanil 500 SC and the fluopyram/prothioconazole SC 400 products. Rat acute oral studies were submitted for both co-formulations. Based on these studies, the fluopyram/pyrimethanil and fluopyram/prothioconazole products show low toxicity to mammals, similar to fluopyram technical. No other toxicity studies were submitted for these products.

         I. Risk Characterization

 Risk characterization is the integration of exposure and effects characterization to determine the ecological risk from the use of fluopyram and the likelihood of effects on aquatic life, wildlife, and plants based on varying pesticide-use scenarios.  The risk characterization provides estimation and a description of the risk; articulates risk assessment assumptions, limitations, and uncertainties; synthesizes an overall conclusion; and provides the risk managers with information to make regulatory decisions.

 A.  Risk Estimation - Integration of Exposure and Effects Data

 Results of the exposure and toxicity effects data are used to evaluate the likelihood of adverse ecological effects on non-target species.  For the assessment of fluopyram risks, the risk quotient (RQ) method is used to compare exposure and measured toxicity values (refer to Appendix F).  Estimated environmental concentrations (EECs) are divided by the most sensitive acute and chronic toxicity values.  The RQs are then compared to the Agency's levels of concern (LOCs). These LOCs, summarized in Appendix F, are the Agency's interpretive policy and are used to analyze potential risk to non-target organisms and the need to consider regulatory action.  These criteria are used to indicate when a pesticide's use as directed on the label has the potential to cause adverse effects on non-target organisms. Details of all RQs are provided in Appendix G.

       1.  Non-target Aquatic Animals and Plants

To assess risk of fluopyram to non-target aquatic animals (fish and invertebrates) and plants (macrophytes and algae), surface water, pore water and sediment EECs for fluopyram were obtained from the Tier 2 model PRZM/EXAMS based on the label-recommended usage scenarios (Table 5). In all instances, this risk assessment used the highest peak (instantaneous) concentration in surface water (for water column dwellers), benthic sediment (for benthic organisms), and benthic pore water (for benthic organisms) generated from the PRZM/EXAMS model to represent acute exposure to aquatic organisms. For chronic risk, the 21-day EECs for fluopyram were compared to available aquatic toxicity data.

             a. Water Column Exposure: Acute and Chronic Risk to Animals

 Fish
 For acute risk to freshwater and estuarine/marine fish species, risk quotients were not calculated because the available toxicity endpoints were not definitive (LC50 > highest test concentration).

For freshwater fish, the chronic risk quotient = 0.001 (Table 17). In EFED risk assessments, endpoints which are considered to be ecologically significant are likely to lead to reductions in survival, growth and/or reproduction of fish. For the submitted early-life stage study with fathead minnow, although sublethal effects including deformed mouth, ventral hematoma, labored respiration, surfacing, dark coloration, swollen belly, loss of equilibrium and lordosis occurred at the third highest treatment level and above (>0.269 mg a.i./L), reductions in survival and growth occurred at only the two highest treatment levels (0.560 and 1.05 mg ai/L). Therefore, 0.269 mg ai/L will be used as the functional NOAEC for chronic risk quotient calculations for freshwater fish.

A chronic risk quotient was not calculated for estuarine/marine fish, because no chronic toxicity data were submitted for this taxon and appropriate acute-to-chronic ratios could not be determined due to non-definitive acute endpoints for all aquatic taxa.

Table 17. Acute and chronic risk quotients (RQs) for evaluating toxic risk of fluopyram exposure to freshwater and estuarine/marine fish.

                                   Organism

                                     LC50
                                 (ug a.i./L)

                                     NOAEC
                                 (ug a.i./L)

                                    EEC[c]
                                     Peak
                                 (ug a.i./L)

                                    EEC[d]
                                    60-Day
                                 (ug a.i./L)

                                     Acute
                                      RQ
                                  (EEC/LC50)

                                    Chronic
                                      RQ
                                  (EEC/NOAEC)
                              Freshwater fish[a]
                                   > 1780
                                      269
                                     7.31
                                     0.286
                                Not calculated
                                     0.001
                           Estuarine/marine fish[b]
                                   > 980
                                 Not available
                                     7.31
                                     0.286
                                Not calculated
                                Not calculated
 [a] Acute toxicity value is based on rainbow trout (Oncorhynchus mykiss) (LC50 >  1.78 mg a.i./L) and chronic toxicity value is based on an early life stage study with fathead minnow (Pimephales promelas) (NOAEC = 0.135  mg a.i./L).
 [b] Acute toxicity value is based on sheepshead minnow (Cyprinodon variegates) LC50 > 0.98 mg a.i./L. Chronic toxicity data were not submitted for estuarine/marine fish.
[c] EEC values are generated from PRZM/EXAMS and represent the most conservative level of acute exposure based on proposed label rates (watermelons, spray and drip irrigation [same EECs for each], STXmelonNMC scenario).
d EEC values are generated from PRZM/EXAMS and represent the most conservative level of chronic exposure based on proposed label rates (watermelons, drip irrigation, Florida cucumber scenario).

 Aquatic Invertebrates
 For acute risk to freshwater and estuarine/marine invertebrate species, risk quotients were not calculated because the available toxicity endpoints were non-definitive (LC50 > highest test concentration). A chronic risk quotient was calculated for freshwater invertebrates (RQ = 0.0006; Table 18). A chronic risk quotient was not calculated for estuarine/marine invertebrates, because no chronic toxicity data were submitted for this taxon and appropriate acute-to-chronic ratios could not be determined due to the lack of definitive acute toxicity endpoints.

Table 18. Acute and chronic risk quotients (RQs) for evaluating toxic risk of fluopyram exposure to freshwater and estuarine/marine aquatic invertebrates.

                                   Organism

                                     LC50
                                 (ug a.i./L)

                                     NOAEC
                                 (ug a.i./L)

                                    EEC[c]
                                     Peak
                                 (ug a.i./L)

                                    EEC[c]
                                    21-Day
                                 (ug a.i./L)

                                     Acute
                                      RQ
                                (peak EEC/LC50)

                                    Chronic
                                      RQ
                              (21-day EEC/NOAEC)
                          Freshwater invertebrates[a]
                                  > 17,000
                                     1214
                                     7.31
                                     0.712
                                Not calculated
                                    0.0006
                       Estuarine/marine invertebrates[b]
                                   > 510
                                 Not available
                                     7.31
                                     0.712
                                Not calculated
                                Not calculated
 [a] Acute and chronic toxicity values are based on studies with the water flea (Daphnia magna)  -  acute EC50 >  17 mg a.i./L and chronic toxicity NOAEC = 1214 ug a.i./L.
 [b] Acute toxicity value is based on saltwater mysid Americamysis bahia LC50 > 0.51 mg a.i./L. Chronic water column toxicity data were not submitted for estuarine/marine invertebrates.
[c] EEC values are generated from PRZM/EXAMS and represent the most conservative level of acute exposure based on proposed label rates (watermelons, spray and drip irrigation [same EECs for each], STXmelonNMC scenario).
[d] EEC values are generated from PRZM/EXAMS and represent the most conservative level of chronic exposure based on proposed label rates (watermelons, drip irrigation, Florida cucumber scenario).

 	b. Sediment Exposure: Acute and Chronic Risk to Benthic Invertebrates

 Comparisons of EECs and sediment toxicity endpoints are provided below to supplement risk estimation to water column organisms. The evaluation of toxic risk to the benthic organisms was approached by assuming equilibrium partitioning of a high Koc compound like fluopyram between the sediment and the pore water (the water found between particulates in the sediment).  Risk to benthic organisms was assessed using two approaches: (1) EECs for sediment were model-generated (PRZM/EXAMS) and compared to the toxicity value as reported for sediment exposure (EC50/LC50/NOAEC) in the sediment toxicity tests (normalized to organic carbon) and (2) EECs for pore water were model-generated (PRZM/EXAMS) and compared to the toxicity value as reported for pore water (EC50/LC50/NOAEC) in the sediment toxicity tests.

 No acute risk quotients were derived for freshwater or estuarine/marine benthic invertebrates via sediment and pore water fluopyram exposure (Table 19). Short-term toxicity data were not provided for freshwater benthic invertebrates and the LC50 endpoint was undefined as no treatment  - related mortality occurred at the highest test concentration (> 2,700,000 ug a.i./kg OC; > 2500 ug a.i./L pore water) of the submitted study with estuarine/marine invertebrates.

Table 19. Acute risk quotients (RQs) for evaluating toxic risk of fluopyram exposure to freshwater and estuarine/marine benthic invertebrates.

                                   Organism

                               LC50 a, b, d, [f]
                               (ug a.i./kg OC)
                                     LC50
                            (ug a.i./L pore water)

                          Peak Sediment EEC c, d, [e]
                               (ug a.i./ kg OC)
                              Peak Pore Water EEC
                          (ug a.i./L pore water) [c]

                                Acute sediment
                                      RQ
                                (peak EEC/LC50)

                                    Acute
                                  pore water
                                      RQ
                               (peak EEC/ LC50)
                          Freshwater invertebrates[a]
                                 Not available
                                 Not available
                                     63.8
                                     0.142
                                Not calculated
                                Not calculated
                       Estuarine/marine invertebrates[b]
                                > 2,700,000
                                   > 2500
                                     63.8
                                     0.142
                                Not calculated
                                Not calculated
 [a] No short-term freshwater sediment toxicity studies were submitted for fluopyram.
 [b] Acute toxicity value is based on the marine amphipod Leptocheirus plumulosus 10-day LC50 > 100 mg TRR/kg sediment and > 2.5 mg TRR/L pore water.
 [c] EEC values are generated from PRZM/EXAMS and represent the most conservative level of exposure based on proposed label rates (watermelons, STXmelonNMC scenario).
 [d] Sediment concentrations and toxicity endpoints were normalized to organic carbon (OC) content based on the following equation:      mg/kg OC =         mg/kg dry weight sediment
                                                   kg TOC/kg dry weight sediment
 [e] The default organic carbon content in PRZM/EXAMS is 4% (0.04 kg TOC/kg dry weight sediment):
                 2.55 ug /kg dry weight sediment           = 63.8 ug a.i./kg OC
 	0.04 kg TOC/kg dry weight sediment
 f The sediment in the 10-day test with Leptocheirus plumulosus contained 3.7% organic carbon (0.037 kg TOC/kg dry weight sediment):
                 100,000 ug /kg dry weight sediment           = 2,700,000 ug a.i./kg OC
 	0.037 kg TOC/kg dry weight sediment

 Chronic risk quotients were derived for both freshwater and estuarine/marine benthic invertebrates via sediment and pore water fluopyram exposure (Table 20).

Table 20. Chronic risk quotients (RQs) for evaluating toxic risk of fluopyram exposure to freshwater and estuarine/marine benthic invertebrates.

                                   Organism

                             NOAEC [a,]b,  d, [f]
                               (ug a.i./kg OC)
                                     NOAEC
                            (ug a.i./L pore water)

                         21-day Sediment EEC [c, d, f]
                               (ug a.i./ kg OC)
                             21-day Pore Water EEC
                          (ug a.i./L pore water) [c]

                               Chronic sediment
                                      RQ
                              (21-day EEC/ NOAEC)

                                   Chronic
                                  pore water
                                      RQ
                              (21-day EEC/NOAEC)
                          Freshwater invertebrates[a]
                                   1,180,000
                                     3800
                                     12.2
                                     0.027
                                    0.00001
                                   0.000007
                       Estuarine/marine invertebrates[b]
                                    643,000
                                     2500
                                     12.2
                                     0.027
                                    0.00002
                                    0.00001
 a The chronic toxicity value for freshwater benthic invertebrates is based on the midge (Chironomus tentans) 54-day NOAEC = 26 mg TRR/kg sediment and 3.8 mg TRR/L pore water.
 [b] The chronic toxicity value for estuarine/marine benthic invertebrates is based on the amphipod Leptocheirus plumulosus 28-day NOAEC = 36 mg TRR/kg sediment and 2.5 mg TRR/L pore water.
 [c] EEC values are generated from PRZM/EXAMS and represent the most conservative level of exposure based on proposed label rates (Florida potato scenario).
 [d] Sediment concentrations and toxicity endpoints were normalized to organic carbon (OC) content based on the following equation:      mg/kg OC =         mg/kg dry weight sediment
                                                   kg TOC/kg dry weight sediment
 [e] The default organic carbon content in PRZM/EXAMS is 4% (0.04 kg TOC/kg dry weight sediment).
                 0.487 ug /kg dry weight sediment           = 12.2 ug a.i./kg OC
 	0.04 kg TOC/kg dry weight sediment
 f The sediment in the 54-day test with Chironomus tentans contained 2.2% organic carbon (0.022 kg TOC/kg dry weight sediment):
                 26,000 ug /kg dry weight sediment        = 1,180,000 ug a.i./kg OC
 	0.022 kg TOC/kg dry weight sediment
   The sediment in the 28-day test with Leptocheirus plumulosus contained 5.6% organic carbon (0.056 kg TOC/kg dry
   weight sediment):
                 36,000 ug /kg dry weight sediment        = 643,000 ug a.i./kg OC
 	0.056 kg TOC/kg dry weight sediment

 		c.  Aquatic Plants

 Acute risk quotients for listed and non-listed vascular and non-vascular aquatic were calculated for the modeled crop use with the highest estimated exposure values (watermelon) for aquatic ecosystems (Table 21).

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

                                   Plant Type
                                      EC50
                                  (μg a.i./L)
                                 NOAEC or EC05
                                  (μg a.i./L)
                       Peak Water Column EEC (μg a.i./L)
                                       RQ
                               endangered species
                              (Peak EEC/EC50) [c]
                                      RQs
                            other non-target plants
                          (Peak EEC/NOAEC or EC05) [d]
 Non-vascular plants [a]
                                      3400
                                      1170
                                      7.31
                                    0.00215
                                     0.006
 Vascular plants [b]
                                      2600
                                      278
                                      7.31
                                    0.00281
                                     0.026
 a For freshwater green algae (Pseudokirchneriella subcapitata) the EC50 = 3.4 mg a.i./L and NOAEC = 1.17 mg a.i./L based on a study with the formulated fluopyram product (41.5% active ingredient). The most sensitive endpoint was cell density.
 [b] For duckweed (Lemna gibba), the EC50 = 2.6 mg a.i./L and NOAEC = 0.278 mg a.i./L based on a study with fluopyram technical. The most sensitive endpoint was frond number based on yield.
[c] Endangered species LOC > 0.05
[d] Acute toxicity LOC > 0.5

       2.  Non-target Terrestrial Animals

 The EFED terrestrial exposure model T-REX was used to estimate exposure and risks in conservative scenarios to avian and mammalian species for four forage food types with spray applications of fluopyram as described in the Exposure Characterization. For this risk assessment, terrestrial EECs as a result of fluopyram spray applications were estimated using the maximum proposed application rate (0.222 lb a.i./A), the maximum number of applications with this rate (2), and the minimum application interval (5 days). Risk quotients were calculated using upper-bound EECs.

 All toxicity reference values for terrestrial animals that are used for calculating risk quotients (RQs) are based on exposure to fluopyram TGAI and are summarized in Table 16. Dietary-based and dose-based and chronic RQs for mammals based on a maximum spray application scenario are listed in Table 22 and Table 23, respectively. . Dietary-based chronic RQs for avian species based on a maximum spray application scenario are summarized in Table 24. All chronic terrestrial RQs can be found in Appendix F.

 		a.  Spray Applications: Acute Risk to Birds and Mammals

 Mammals
 Acute dose-based RQ values for mammalian receptors were not calculated because the results of the definitive submitted acute oral toxicity studies on mammals did not allow calculation of a definitive LD50 values.

 Birds
 Acute dose- or dietary-based RQs for birds were not calculated because definitive LD50 and LC50 values were not available.

             b. Spray Applications: Chronic Risk to Birds and Mammals

 Mammals
 Dietary-based RQs were calculated using EECs expressed in terms of residue concentration for the various forage categories, and the toxicity value (NOAEC) is expressed in units of dietary concentration. Dose-based RQs were calculated using EECs expressed in terms of a dose concentration for the various forage categories and the estimated toxicity value (NOAEL). The dose-based EECs are calculated by using the estimated dietary concentrations and assuming the laboratory rat consumes 5% of its body weight daily. Three weight categories (or sizes) were considered for dose-based risk calculations (Tables 22 and 23).

 Table 22. Dietary-based chronic RQs for mammals exposed to fluopyram based on upper-bound residues on short grass, tall grass, broadleaf plants/small insects, and fruits/pods/seeds/large insects as calculated by T-REX
                      Mammalian Chronic Risk Quotients[*]
                                  Short Grass
                                   Tall Grass
                               Broadleaf Plants/
                                 Small Insects
                               Fruits/Pods/Seeds/
                                 Large Insects
                                      7.58
                                      3.58
                                      4.39
                                      0.49
 [*] These values were calculated using the maximum application rate (0.222 lb a.i./A), the maximum number of applications (2), the minimum application interval (5 days), and a chronic NOAEC = 13 mg a.i./kg diet in rats and a default chemical foliar half-life of 35 days.

 Table 23. Dose-based chronic RQs for small (15g), intermediate (35g), and large (1,000g) mammals exposed to fluopyram based on upper-bound residues on short grass, tall grass, broadleaf plants/small insects, fruits/pods/large insects and seeds as calculated by T-REX

                      Mammalian Chronic Risk Quotient[*]

                                  Body Weight
                                      (g)

                                  Short Grass
                                   Tall Grass
                               Broadleaf Plants/
                                 Small Insects
                                  Fruits/Pods/
                                 Large Insects
                                     Seeds
                                       15
                                     67.76
                                     31.06
                                     38.12
                                      4.24
                                      0.94
                                       35
                                     57.88
                                     26.53
                                     32.56
                                      3.62
                                      0.80
                                      1000
                                     31.03
                                     14.22
                                     17.45
                                      1.94
                                      0.43
 [*] These values were calculated using the maximum application rate (0.222 lb a.i./A), the maximum number of applications (2), the minimum application interval (5 days), and an estimated chronic NOAEL = 0.75 mg a.i./kg body weight/day in rats based on the chronic dietary NOAEC = 13 mg ai/kg diet and a default chemical foliar half-life of 35 days.

 Birds
 For birds, chronic RQs were derived using a dietary-based chronic toxicity value. Dietary-based RQs were calculated using EECs expressed in terms of residue concentration for the various forage categories, and the toxicity value (NOAEC) is expressed in units of dietary concentration (Table 24).

 Table 24. Dietary-based chronic RQs for birds exposed to fluopyram based on upper-bound residues on short grass, tall grass, broadleaf plants/small insects, and fruits/pods/seeds/large insects as calculated by T-REX
                        Avian Chronic Risk Quotients [a]
                                  Short Grass
                                   Tall Grass
                               Broadleaf Plants/
                                 Small Insects
                               Fruits/Pods/Seeds/
                                 Large Insects
                                      2.17
                                      1.00
                                      1.22
                                      0.14
 [a] These values were calculated using the maximum application rate (0.222 lb a.i./A), the maximum number of applications (2), the minimum application interval (5 days), and a chronic NOAEC = 46.70 mg a.i./kg diet in bobwhite quail and a default chemical foliar half-life of 35 days.

 	3.  Non-target Terrestrial and Semi-Aquatic Plants

 A preliminary run of TERR-PLANT was conducted using the maximum application scenarios for ground application (labeled use rates for watermelons) and aerial application (labeled use rates for almond, pecan, pistachios and tree nuts). All EECs ranged from 0.002 (spray drift) to 0.047 (semi-aquatic areas) lbs a.i./A for ground application and from 0.011 (spray drift) to 0.055 (semi-aquatic areas) lbs a.i./A for aerial application.

 Compared to the available toxicity studies, in the vegetative vigor study, sugarbeet had the highest level of inhibition in dry weight, a 20.2% reduction in comparison to the negative control at a fluopyram application rate of 0.222 lbs a.i./A. The rate applied in the Tier I seedling emergence test, 0.444 lbs a.i./A, was greater than the maximum application rate of 0.222 lbs a.i./A. Because buckwheat showed a 50.4% reduction in dry weight at 0.444 lbs a.i./A in the seedling emergence test, a Tier II test was conducted (MRID 47372349). The most sensitive endpoint was biomass. No clear dose-dependent pattern for effects on biomass was observed due to high variance. Compared to the negative control, reductions in biomass were 12.3, 1.6, 21.3, 40.1 and 6.2% at nominal concentrations of 0.028, 0.056, 0.111, 0.222, and 0.444 lbs a.i./acre respectively.

 B.  Risk Description - Interpretation of Direct Effects

 The purpose of the risk description is to characterize risk and incorporate other lines of evidence including non-standard methods and data.

       1.  Risks to Aquatic Organisms

 		a.  Aquatic Animals and Plants:  Water Column Exposure

 Acute Risk to Fish and Aquatic-phase Amphibians
 For acute risk to freshwater and estuarine/marine fish species (and aquatic-phase amphibians using the surrogate species approach), risk quotients were not calculated because the available toxicity endpoints were non-definitive (LC50 > highest test concentration). However, as shown in Table 13, the peak estimated exposure concentration for aquatic organisms (7.31 ug a.i./L) is more than two orders of magnitude less than the highest tested fluopyram technical concentrations in acute toxicity tests that caused no adverse effects to freshwater and estuarine/marine fish species (LC50 > 0.98 mg a.i./L and NOAEC = 0.98 mg a.i./L for sheepshead minnow; LC50 >1.78 mg a.i./L and NOAEC = 1.78 mg a.i./L for rainbow trout). No mortality or sublethal effects were observed in acute fish studies with the fluopyram active ingredient. In studies with the formulated product (fluopyram 500 SC, 41.5% active ingredient), sublethal effects at the 8.27- 46.4 mg ai/L treatment groups included fish lying on the bottom of the test chamber, dark coloration, labored respiration, mucous secretion from intestine, surfacing, and lying on side/back (NOAEC =1.31 mg a.i./L). However, these effects were observed at much higher concentrations than is expected to occur in the environment.

 Acute risk to freshwater and saltwater fish from fluopyram use is expected to be low.

 Chronic Risk to Fish and Aquatic-phase Amphibians
 The level-of-concern for chronic risk to aquatic organisms (LOC > 1.0) was not exceeded for freshwater fish (and aquatic-phase amphibians using the surrogate species approach) (RQ = 0.001; Table 17). A chronic risk quotient was not calculated for estuarine/marine fish, because no chronic toxicity data were submitted for this taxon and appropriate acute-to-chronic ratios could not be determined due to lack of available data on definitive acute toxicity endpoints for any aquatic taxa.

 Chronic risk to fish species resulting from the proposed uses of fluopyram appears to be low. Because the expected exposure concentration of fluopyram (60-day EEC = 0.286 ug a.i./L) is much lower than the levels at which adverse chronic effects to fish are expected to occur (NOAEC =  0.135 mg a.i./L and LOAEC = 0.269 mg a.i./L for fathead minnow), the submission of a fish full life cycle test or additional chronic testing with estuarine/marine fish is not expected to greatly influence the overall risk picture for fluopyram.

 Acute Risk to Aquatic Invertebrates
For acute risk to freshwater and estuarine/marine invertebrate species, risk quotients were not calculated because the available toxicity endpoints were non-definitive (LC50 > highest test concentration). However, as shown in Table 18, the peak estimated exposure concentration for aquatic organisms (7.31 ug a.i./L or 0.00731 mg a.i./L) is at least two orders of magnitude less than the highest tested fluopyram concentrations in the available acute toxicity tests, ranging from 0.51 mg a.i./L to 38.2 mg a.i./L, in which no EC50 values were definitively calculated due to low mortality.

No immobility (assumed to be equivalent to death) or sublethal effects were observed in tests with technical grade fluopyram and water flea (Daphnia magna; EC50 >17 mg a.i./L and NOAEC=17 mg a.i./L). However, immobility was observed at the two highest treatment levels (20.4 and 38.2 mg a.i./L) in a Daphnia magna test with fluopyram end-use product (EC50 > 38.2 mg a.i./L and NOAEC =11.6 mg a.i./L). In addition, the submitted acute study with the saltwater mysid resulted in 10% mortality in the highest treatment group, 0.51 mg ai/L (LC50:  >0.51 mg ai/L, NOAEC = 0.27 mg ai/L). Nonetheless, the peak estimated exposure concentration for aquatic organisms (7.31 ug a.i./L or 0.00731 mg a.i./L; Table 13) is still two orders of magnitude less than the level at which immobility was observed in the these aquatic invertebrate tests. Therefore, based on currently available information, acute risk to aquatic invertebrate species due to water column exposure appears to be low following application of fluopyram from the proposed uses.

 Chronic Risk to Aquatic Invertebrates
 The level-of-concern for chronic risk to aquatic organisms (LOC > 1.0) was not exceeded for freshwater invertebrates (RQ = 0.0006; Table 17).

 A chronic risk quotient was not calculated for estuarine/marine invertebrates, because no chronic toxicity data were submitted for this taxon and appropriate acute-to-chronic ratios could not be determined due to the lack of definitive acute toxicity endpoints for any aquatic species. One additional way to approximate toxicity to this taxon is to use the available chronic estuarine/marine benthic invertebrate toxicity endpoint based on pore water concentrations and compare this chronic exposure concentrations in the water column. This approach assumes that equal toxicity exists for water column and benthic invertebrates. This assumption is employed in the equilibrium partitioning (EqP) approach (Di Toro et al, 1991) when deriving sediment benchmarks when only data for water column species is available (US EPA, 2005 and US EPA, 2002). Chronic data on fluopyram were submitted for estuarine/marine benthic invertebrates. The EEC is 0.712 ug a.i./L  for the use scenario with the highest 21-day water column estimated exposure (watermelon) (Table 11). In a 28-day test with the estuarine amphipod Leptocheirus plumulosus, the NOAEC was 2.5 mg TRR/L pore water (or 2500 ug a.i./L), and the total toxic residues are assumed to be predominantly the parent chemical fluopyram. The highest chronic water column EEC (Table 12) is approximately four orders of magnitude less than the estuarine/marine benthic invertebrate NOAEC based on pore water concentrations. Some uncertainty are inherent in this comparison, due to differences in exposure routes of the toxicity tests, water-column only exposure vs. sediment ingestion in combination with pore water, as well as the life histories of the organisms. In addition, the study was considered supplemental due to the lack of a clear dose-response for reproductive endpoints. However, in the absence of additional data, this is considered the best available approximation for chronic risk to estuarine/marine invertebrates.

 Based on these lines of evidence, low chronic risk is presumed for aquatic invertebrates in the water column.

 Aquatic Plants

No acute risk quotients for non-vascular or vascular aquatic plants exceeded any of the levels-of-concern (1.0) for the modeled crop use with the highest estimated exposure values (watermelons) (Table 21). Risk quotients ranged from 0.00215 to 0.0263. The most sensitive endpoints for vascular and nonvascular plants were similar.

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

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

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

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

 		b.  Aquatic Animals:  Sediment Exposure

 Fluopyram shows the potential to bind to particulate and organic carbon (with a high log Kow = 3.314, although the log Koc = 439 is not particularly high), which increases the likelihood of occurrence of this chemical in sediment. Exposure to this sediment can result in a direct impact to aquatic life through respiration, ingestion, dermal contact, as well as indirect impact through alterations of the food chain. Coupled with fluopyram's expected persistence in aerobic and anaerobic environments, sediment-bound fluopyram could present a toxicity risk for benthic and epibenthic aquatic life, and aquatic ecosystems in general.  Therefore, risk to benthic organisms was considered in addition to risk to water-column dwelling organisms.

 No acute risk quotients were derived for freshwater or estuarine/marine benthic invertebrates via sediment and pore water fluopyram exposure (Table 19). Short-term toxicity data was not provided for freshwater benthic invertebrates and the LC50 endpoint was undefined (> 2,700,000 ug a.i./kg OC; > 2500 ug a.i./L pore water) in the submitted study with estuarine/marine invertebrates. Based on information in the available, the predicted environmental concentrations for the modeled crop use with the highest peak aquatic EEC value (watermelons) are more than four orders of magnitude lower than the highest fluopyram levels tested that did not elicit adverse effects on the survival of estuarine/marine benthic invertebrates.  The EqP approach, as described above in the water column exposure section, was also used to approximate acute risk to freshwater benthic invertebrates, as no toxicity studies were submitted for this taxon. The levels at which no adverse effects were observed acute water column toxicity tests with freshwater invertebrate (EC50>17 mg a.i./L) is 5 orders of magnitude greater than the predicted maximum peak pore water concentrations (0.142 ug a.i./L pore water). Therefore, overall acute risk to freshwater and estuarine/marine benthic organisms is expected to be low. In addition, no chronic levels-of-concern were exceeded and chronic risk to freshwater or estuarine/marine benthic invertebrates is not expected from current proposed uses of fluopyram (Table 20).

       3.  Risks to Terrestrial Organisms

             a.  Spray Applications: Acute and Chronic Risk to Birds and Mammals

 Acute Risk to Birds, Reptiles and Terrestrial-phase Amphibians
 Risk quotients were not calculated for acute risk to birds (and reptiles and terrestrial-phase amphibians using the surrogate species approach) based on the nondefinitive endpoints in the submitted acute and dietary studies (LD50 > 2000 mg ai/kg bw; LC50 > 4785 mg ai/kg bw). However, mortality and sublethal effects were noted. In the acute oral study with bobwhite quail, mortalities were observed in all treatment levels, ranging from 1/10 birds at 500 mg ai/kg bw (lowest treatment level) and 4/10 birds at the 2000 mg ai/kg bw (highest treatment level. In addition, One mortality was also observed in the limit test with zebra finch (1/6 birds). A second test was conducted and no mortality occurred. However, sublethal clinical effects such as ataxia, piloerection, wing droop and uncoordination were observed in the limit test.

 In the dietary tests, there were no treatment-related effects on mortality, clinical signs of toxicity, body weight, or food consumption to the tested species, mallard duck (dietary LC50 >4604 mg ai/kg diet). However, based upon a notable increase in the incidences of red pancreases in surviving birds at the 4604 mg ai/kg diet level, the NOAEC was 2307 mg ai/kg diet (note that this effect does not appear to be directly linked to the typical US EPA ecological risk assessment endpoints of survival, growth or reproduction of an organism). In a study with northern bobwhite, exposure to fluopyram technical resulted in a dietary LC50 >4785 mg ai/kg diet.  Based upon treatment-related reductions in food consumption at all treatment levels, the NOAEC <279 mg ai/kg diet. A statistically-significant reduction in body weight also occurred in birds from the 4785 mg ai/kg diet level during the exposure period.

For the highest use scenario (watermelons and strawberries), the most conservative acute dose-based and dietary EECs for birds would be 101.54 ppm (short grass) and 115.64 ppm (15-gram bird, short grass), respectively (assuming the default 35-day half-life). Therefore, these observations of mortality and sublethal effects occurred at levels that are approximately 2.7 to 4.3 times higher than the upper bound EECs of the highest fluopyram use scenario. Some uncertainty exists in defining the lowest level at which mortality or sublethal effects would occur, since no NOAEC was established in the most sensitive acute oral and dietary studies. Therefore, acute risk to avian species cannot be entirely precluded.

 Chronic Risk to Birds, Reptiles and Terrestrial-phase Amphibians
 The dietary-based chronic RQs for avian species (and reptiles and terrestrial-phase amphibians using the surrogate species approach) exceed the chronic risk LOC (EEC/NOAEC >= 1) for three of the four dietary items (short grass, tall grass and broadleaf plants/small insects). The dietary-based chronic avian RQs for the fruits/pods/seeds/large insects dietary category did not exceed the chronic risk level of concern (RQ range = 0.14 to 2.17; Table 24). Therefore, chronic risk concerns exist for avian species. Potential chronic effects to avian species, such as reduction in 14-day survivor body weight for chicks, could occur at environmentally-relevant exposure concentrations of fluopyram following proposed label use rates.

 Exceedances of the chronic levels-of-concern for this taxa occurred for all crops on the proposed label, with the exception of cherry (see detailed risk quotients in Appendix F).

 Acute Risk to Mammals
 Results of oral toxicity study conducted on rats show that fluopyram TGAI is practically non-toxic to mammals on an acute basis (LD50 > 2000 mg a.i./kg bw). No mortality or sublethal effects were observed in this study.

For the highest use scenario (watermelons and strawberries), the most conservative acute dose-based EEC for mammals is 96.81 ppm (15-gram mammal, short grass), assuming the default 35-day half-life. The highest fluopyram concentration in the acute oral study with rats did not result in any mortality or sublethal effects and is approximately 20 times greater than the highest EEC predicted for the most conservative use scenario. Therefore, acute dose-based risk to mammalian species is presumed to be low.

 Chronic Risk to Mammals
 For the maximum application scenario considered in this risk assessment (watermelons and strawberries), dietary-based RQs for chronic risk to mammalian species are above the chronic risk level-of-concern (EEC/NOAEC >= 1) for three of the four dietary items (short grass, tall grass and broadleaf plants/small insects). The dietary-based chronic mammalian RQs for the fruits/pods/seeds/large insects dietary category did not exceed the chronic risk level of concern (RQ range = 0.49 to 7.81; Table 22).

 Dose-based RQs for chronic risk to mammalian species exceed the chronic LOC for all dietary routes of exposure with the exception of seeds (overall RQ range = 0.43 to 67.76; Table 23).  Specifically, chronic RQs exceed the LOC for all size classes of mammals feeding on short grass (RQ range = 31.03 to 67.76), tall grass (RQ range = 14.22 to 31.06), broadleaf plants/small insects (RQ range = 17.45 to 38.12) and fruits/pods/large insects (RQ range = 1.94 to 4.24). The chronic LOC is not exceeded for mammals of any size feeding on seeds (RQ range = 0.43 to 0.94).

 Exceedances of the chronic levels-of-concern for this taxa occurred for all crops on the proposed label (see detailed risk quotients in Appendix F).

 Based on this analysis, the potential for chronic adverse affects to mammalian species could occur at environmentally-relevant exposure concentrations. These potential effects include decreased body weight in adults and offspring, as well as reduced food consumption.

 		b.  Non-target Terrestrial Invertebrates

 US EPA does not evaluate the potential exposure of terrestrial insects to pesticides or quantitatively evaluate risk to this taxonomic group in new chemical screening level assessments. The risk characterization for terrestrial insects and mites that follows below is based solely on available toxicity data.

 Results of the submitted acute toxicity studies demonstrate that fluopyram TGAI and the fluopyram formulated product show little toxicity to honey bees on an acute contact or oral basis (acute oral:  LD50 > 97.7 μg a.i./bee for fluopyram TGAI and LD50 > 89 μg a.i./bee for formulated fluopyram ; acute contact:  LC50 > 95.5 μg a.i./bee for fluopyram TGAI and an LC50 > 83.2 μg a.i./bee for formulated fluopyram).

 Additional studies with fluopyram technical and the end-use product (Fluopyram SC 500, 41.8% active ingredient) were submitted for other nontarget terrestrial invertebrates, including predatory mite (Typhlodromus pyri), rove beetle (Aleochara bilineata, springtail (Folsomia candida), soil mite (Hypoaspis aculeifer) and earthworm (Eisenia fetida). None of these studies resulted in an LC50 or EC50, as 50% mortality did not occur at the highest treatment level in any of the tests (LC50s ranged from >20.31 mg a.i./kg dw soil to >1000 mg a.i./kg dw soil for earthworms; LD50 > 801.8 mL a.i./ha for rove beetles; LC50 >415 mg a.i./kg dw soil for soil mites and springtails; LC50 >825.9 mL a.i./ha for parasitic wasp; LC50 >834.2 mL a.i./ha for predatory mite).  The highest single application rate of 0.222 lbs a.i./acre (6.84 fl oz product/acre) is equivalent to 207 mL a.i./ha, which is lower than the highest levels tested in comparable units. Therefore, acute toxicity to these additional nontarget terrestrial invertebrates appears to be low.

In two 14-day toxicity studies, statistically significant weight loss (10-23%) was observed in earthworms exposed to fluopyram at treatment levels >131 mg a.i./kg dw of soil. No adverse effects on mortality or growth were observed in a 28-day subchronic study with earthworms exposed to lower levels of the end-use product (1.85 to 20.31 mg a.i./kg dw soil), but a reduced number of surviving juveniles occurred at the highest treatment levels (8-23% reduction compared to the control, NOAEC = 3.27 mg a.i./kg dw soil). In the 28-day reproduction test conducted with the springtail, the test organisms were exposed to nominal application rates of 26.1 to 415 mg a.i./kg dw soil. After 28 days, significant mortality occurred (29.5-45.5%) and the number of juveniles was significantly reduced (36.5-36.9%) at the two highest treatment levels (207.5 and 415 mg a.i./kg dw soil). Based on submitted terrestrial field dissipation studies, the maximum soil concentration following fluopyram application at 0.446 lb a.i/A (twice the maximum label rate) is 286 ug a.i./kg soil (MRIDs 47567001, 47567002, 47567003, 47567004 and 47567005). This maximum empirical soil concentration is approximately 1-3 orders of magnitude less than the exposure concentrations that caused adverse reproductive effects in the studies with earthworms and springtails. Therefore, the potential for adverse effects to soil-dwelling invertebrates following fluopyram application appears to be low, based on the currently available information.

 		c.  Terrestrial Plants

 The maximum modeled EECs ranged from 0.002 (spray drift) to 0.047 (semi-aquatic areas) lbs a.i./A for ground application and from 0.011 (spray drift) to 0.055 (semi-aquatic areas) lbs a.i./A for aerial application. Compared to the available toxicity studies, in the vegetative vigor study, sugarbeet had the highest level of inhibition in dry weight, a 20.2% reduction in comparison to the negative control at a fluopyram application rate of 0.222 lbs a.i./A. Therefore, it does not appear as if fluopyram spray applications will have any direct phytotoxic effects on the height or weight of exposed monocot or dicot species at these proposed label rates.

 The rate applied in the Tier I seedling emergence test, 0.444 lbs a.i./A, was greater than the maximum application rate of 0.222 lbs a.i./A. Because buckwheat showed a 50.4% reduction in dry weight at 0.444 lbs a.i./A in the seedling emergence test, a Tier II test was conducted (MRID 47372349). The most sensitive endpoint was biomass. No clear dose-dependent pattern for effects on biomass was observed due to high variance. Compared to the negative control, reductions in biomass were 12.3, 1.6, 21.3, 40.1 and 6.2% at nominal concentrations of 0.028, 0.056, 0.111, 0.222, and 0.444 lbs a.i./acre respectively. Therefore, it appears as if some reduction in biomass following seedling emergence of certain dicot species, such as buckwheat, may occur at environmentally relevant concentrations of fluopyram exposure following the proposed spray application rates.

       4.  Review of Incident Data

 Because fluopyram has not been previously approved for use in the United States, there are no incident reports for this chemical.

 	5.  Threatened and Endangered Species Concerns

For listed species assessment purposes, the action area is considered to be the area affected directly or indirectly by the Federal action and not merely the immediate area involved in the action. At the initial screening-level, the risk assessment considers broadly described taxonomic groups and so conservatively assumes that list species within those broad groups are collocated within the pesticide treatment area. This means that terrestrial plants and wildlife are assumed to be located on or adjacent to the treated site and aquatic organisms are assumed to be located in a surface water body adjacent to the treated site. The assessment also assumes that the listed species are located within an assumed area which has the relatively highest potential exposure to the pesticide, and that exposures are likely to decrease with distance from the treated area.

If the assumptions associated with the screening-level action area result in RQs that are below the listed species LOCs, "no effect," determination conclusion may be made with respect to listed species in that taxa (for direct effects), and no further refinement of the action is necessary.  Furthermore, RQs below the listed species LOCs for a given taxonomic group indicate no concern for indirect effects upon listed species that depend upon the taxonomic group as a resource.  However, in situations where the screening assumptions lead to RQs in excess of the listed species LOCs for a given taxonomic group, a potential "may affect," conclusion exists and may be associated with direct effects on listed species belonging to that taxonomic group or may extend to indirect effects upon listed species that depend on that taxonomic group as a resource.  In such cases, additional information on the biology of the listed species, the locations of these species, and the locations of use sites could be considered along with available information on the fate and transport properties of the pesticide to determine the extent to which screening assumptions regarding an action area apply to a particular listed organism.  These subsequent refinement steps could consider how this information would impact the action area for a particular listed organism and may potentially include areas of exposure that are downwind and downstream of the pesticide use site.

In conducting a screen for indirect effects, direct effects LOCs for each taxonomic group are used to make inferences concerning the potential for indirect effects upon listed species that rely upon non-listed organisms in these taxonomic groups as resources critical to their cycle.  Pesticide use scenarios resulting in RQs that are below all direct effect listed species LOCs for all taxonomic groups assessed are considered of no concern for risks to listed species either by direct or indirect effects.

For fluopyram, the potential direct effects to listed species should they co-occur with application sites are indicated for mammals and birds (based on consumption of short grass, tall grass and broadleaf plants/small insects).

 Screening-level chronic RQs for avian and mammalian species exceed the chronic endangered species risk LOCs. In addition, acute risk to avian species could not be discounted. Listed species LOCs are not exceeded for any other taxonomic group assessed (aquatic animals, terrestrial or aquatic plants, nontarget invertebrates).  For the maximum proposed fluopyram application rates, there may be a potential concern for direct effects to the following groups of organisms:

 Birds
 Mammals
 Terrestrial-phase reptiles
 Terrestrial-phase amphibians
 Terrestrial plants

A spatial co-occurrence analysis would be necessary to delineate the action area.

 C.  Description of Assumptions, Limitations, Uncertainties, Strengths and Data Gaps

       1.  Exposure for All Taxa

 There are a number of areas of uncertainty in the aquatic and terrestrial risk assessments.  The toxicity assessment for terrestrial and aquatic plants and animals is limited by the number of species tested in the available toxicity studies.  Use of toxicity data on representative species does not provide information on the potential variability in susceptibility to acute and chronic exposures.

 For each proposed use, the risk assessment is based on the maximum application rate on the proposed label. The frequency at which actual uses approach these maximum scenarios is dependent on the resistance to the pesticide, the timing of applications, and market forces. Exposure and risks could be overestimated if the actual application rates, frequency of application, or number of applications are lower than the input parameters used for the conservative exposure scenario that was modeled.  However, if there are conditions under which there is more than one growing season for a crop within a single year, exposure estimates and risk to aquatic and terrestrial organisms could be significantly underestimated.

       2.  Exposure for Aquatic Species

 This Tier II risk assessment relies on best available estimates of environmental fate and physicochemical properties, maximum application rate of fluopyram, maximum number of applications, and the shortest interval between applications.  However, several uncertainties and model limitations are noted and should be considered in interpreting the results of this aquatic risk assessment.

 ::	The frequency at which actual fluopyram uses approach the use estimates modeled is dependent on resistance to the insecticide, timing of applications, and market forces. In general, model output values represent the upper-bound estimates of concentrations that might be observed in surface water due to the application of fluopyram, given available data and model limitations.

 ::	Although there are uncertainties associated with using the standard PRZM/EXAMS runoff scenario (10 ha field draining into 20,000 m[3] pond with no outlet) for an aquatic exposure assessment, it is designed to represent pesticide exposure from an agricultural watershed impacting a vulnerable aquatic environment.  Extrapolating the risk conclusions from this standard pond scenario may either underestimate or overestimate the potential risks.

 ::	Major uncertainties associated with the standard runoff scenario include the physical construct of the watershed and representation of vulnerable aquatic environments for different geographic regions.  The physicochemical properties (pH, redox conditions, etc.) of the standard farm pond are based on a Georgia farm pond.  These properties are likely to be regionally specific because of local hydrogeological conditions.  Any alteration in water quality parameters may impact the environmental behavior of a pesticide.  The farm pond represents a well mixed, static water body.  Because the farm pond is a static water body (no flow through), it does not account for pesticide removal through flow through or water releases.  The lack of flow through the farm pond provides an environmental condition for accumulation of persistent pesticides.  The assumption of uniform mixing does not account for stratification due to thermoclines (e.g., seasonal stratification in deep water bodies).  Additionally, the dimensions of the standard runoff scenario assume a watershed area to water body volume ratio of 10 ha: 20,000m[3].  This ratio is recommended to maintain a sustainable constructed pond in the Southeastern United States.  The use of higher watershed area to water body volume ratios (as recommended for sustainable ponds in drier regions of the United States) may lead to higher pesticide concentrations when compared to the standard watershed area to water body volume ratio.

 ::	The standard runoff scenario assumes uniform soils and agronomic management practices across the standard 10 hectare field.  Soils can vary substantially across even small areas; this variation is not reflected in the model simulations.  Additionally, the impact of unique soil characteristics and soil management practices (e.g., tile drainage) are not considered in the standard runoff scenario.  The assumption of uniform site and management conditions is not expected to represent some site-specific conditions.  Extrapolating the risk conclusions from the standard pond scenario to other aquatic habitats (e.g., marshes, streams, creeks, and shallow rivers, intermittent aquatic areas) may either underestimate or overestimate the potential risks in those habitats.

 ::	For an acute risk assessment, there is no averaging time for exposure.  A peak concentration, with a 1 in 10 year return frequency, is assumed.  The use of the peak concentration in the calculation of risk quotients assumes that exposure is sufficient to elicit acute effects comparable to those observed over more protracted exposure periods tested in the laboratory, typically 48 to 96 hours.  In the absence of data regarding time-to-toxic event analyses and latent responses to peak exposure, the degree to which risk is overestimated cannot be quantified.

       3.  Exposure for Terrestrial Species

 This risk assessment relies on the best available estimates of environmental fate and physicochemical properties, maximum application rate of fluopyram, maximum number of applications, and the shortest interval between applications.  However, several uncertainties and model limitations are noted and should be considered in interpreting the results of this terrestrial risk assessment.

 Choice of Half-life Value Used in Terrestrial Exposure Modeling
 One source of uncertainty for the terrestrial risk assessment relates to the magnitude of the estimated exposure concentrations representing terrestrial exposure to fluopyram is based on a 35-day foliar dissipation half-life. When data are absent, US EPA assumes a 35-day foliar dissipation half-life as an input to T-REX model. The use of the 35-day half-life is based on the highest reported value (36.9 days) on the foliar dissipation rate of a wide range of pesticides, as reported in Willis and McDowell (1987).

Some data were submitted by the registrant regarding the foliar dissipation half-life. These magnitude of residue studies were conducted on different crops than those on the proposed label. Residue decline trials were conducted on corn, sorghum, wheat, cabbage, mustard greens, lettuce, spinach, radish, sugar beet, turnip, soybean, Bermuda grass and timothy grass (MRIDs 47372606, 47567010, 47567011, 47567014, 47567015, 47567016, 47567025 and 47567026). Because the tested crops differ from the crops on the proposed label, these studies were not submitted to or reviewed by the Health Effects Division, as is typical for foliar dissipation studies. A summary of the data (MRID 47567008) and the individual study reports were preliminarily reviewed by the Environmental Fate and Effects Division. The residue trials report fluopyram concentrations following a single foliar application of fluopyram 500 SC at the maximum allowable rate (reported to be 0.223 lbs a.i./A which is slightly higher than the 0.222 lbs a.i/A used for modeling, presumably due to rounding differences). Fluopyram concentrations were analyzed in the homogenized above-ground foliage, and extracted residues were quantified using high performance liquid chromatography-electrospray ionization/tandem mass spectrometry. Sampling occurred at day 0 and four additional time points until day 10-28 post-application, depending on the study. All residue trials were conducted in typical growing areas for the examined crop. Half-lives were calculated assuming a first-order decay rate.

One potential concern exists for using the empirical half-lives from the trials. Rainfall and/or sprinkler irrigation occurred in all of the trials to varying degrees, ranging from 0.1 to 11.5 inches rainfall and 0.99 to 2.50 inches of irrigation water. When precipitation occurs, this can reduce the residues present on plant surfaces. Regardless, an additional analysis was conducted to explore how changes in the half-life used in terrestrial exposure modeling may affect risk conclusions.

 Based on this information, it appears that the foliar dissipation half-life could be lower than the default value of 35 days, and the terrestrial EECs may be overestimated to some degree. The range of half-lives calculated from the field trials ranged from 0.76 to 9.27 days, with the exception of an estimated half-life of 45.6 days in one trial with corn. In addition to appearing to be an outlier in the data set, the concentrations in this corn trial were highly variable and suggest that the results are questionable. From the available data in the 15 other field trials, excluding the suspect corn trial, the 90[th] percentile of the mean half-life values was calculated. This alternate half-life value for fluopyram is 7.37 days (Note:  If the 45.6 half-life value from the corn trial is added to the data set, the 90[th] percentile of the mean changes slightly to a half-life value of 8.45 days). This differs slightly from the suggested value in the summary report, 4.08 days, which is based on the overall mean of the 15 trials.

 The highest use scenario, the lowest use scenario, and the scenario with the greatest number of applications were run again in T-REX using 7.37-day dissipation half-life, in addition to the 35-day half-life used to calculate risk quotients. The highest and lowest use scenarios were used to bound potential exposure and risk estimates. When multiple applications are modeled, residue concentrations resulting from the final application and remaining residue from previous applications are summed. The maximum concentration calculated (out of the 365 days) is the EEC used to estimate potential risk to birds and mammals. Therefore, the number of applications is an important consideration for comparing estimated exposure based on potential differences in the half-life of a chemical. To account for the influence, the scenario with the highest number of applications was also included in this comparison.

 Based on this exploratory analyses, EECs are reduced by approximately 15% of those calculated using a 35-day half-life when a 7.37-day half-life is used for the maximum and minimum use scenario. For the use scenario with the highest number of applications, EECs are reduced by about 25% when a 7.37-day half-life is used instead of the default 35 days. Despite these reductions in EECs, using a 7.37-day half-life would still result in chronic dietary-based exceedances for birds (RQs range from 0.05 to 1.85) and mammals (RQs range from 0.15 to 6.77) (Table 25-27).  This comparison suggests that even if the foliar dissipation half-life for fluopyram is the lower value reported in the residue decline trials, the chronic risks to birds and mammals as a result fluopyram exposure would remain similar.

 Table 25.  Terrestrial EECs (ppm) estimated for fluopyram use scenarios with 35-day and 7.37-day foliar dissipation half-lives using upper-bound Kenaga values

                          Watermelons and Strawberries
                            max exposure scenario[a]
                                   Cherries
                            min exposure scenario[b]
                                    Potatoes
                scenario with highest number of applications[c]
                                  Forage Type

                                35-day half-life
                               7.37-day half-life
                                35-day half-life
                               7.37-day half-life
                                35-day half-life
                               7.37-day half-life
                                  short grass
                                     101.54
                                     86.57
                                     42.08
                                     35.88
                                     60.19
                                     44.50
                                   tall grass
                                     46.54
                                     39.68
                                     19.29
                                     16.44
                                     27.59
                                     20.39
                       broadleaf plants and small insects
                                     57.11
                                     48.70
                                     23.67
                                     20.18
                                     33.86
                                     25.03
                           fruits/pods/large insects
                                      6.35
                                      5.41
                                      2.63
                                      2.24
                                      3.76
                                      2.78
 [a]  The maximum application rate for watermelons and strawberries is 0.222 lbs a.i./A, with a 5-day application interval and 2 applications.
 [b] The maximum application rate for cherries is 0.092 lbs a.i./A, with a 5-day application interval and 2 applications. This scenario for cherries results in the lowest EECs from any of proposed application rates for any crop on the Fluopyram 500 SC label. All scenarios for terrestrial modeling use the maximum application rate for any given use pattern. Therefore, these numbers represent the exposure from the maximum application rate for the crop with the lowest proposed use rates of fluopyram.
 [c] The maximum aerial application rate for potatoes is 0.092 lbs a.i./A, with 5-day application interval and 3 applications. The aerial scenario for potatoes has the highest number of applications for any crop on the Fluopyram 500 SC label.

 Table 26.  Chronic avian dietary RQs estimated for fluopyram use scenarios with 35-day and 7.37-day foliar dissipation half-lives using upper-bound Kenaga values

                          Watermelons and Strawberries
                            max exposure scenario[a]
                                   Cherries
                            min exposure scenario[b]
                                    Potatoes
                scenario with highest number of applications[c]
                                  Forage Type

                                35-day half-life
                               7.37-day half-life
                                35-day half-life
                               7.37-day half-life
                                35-day half-life
                               7.37-day half-life
                                  short grass
                                      2.17
                                      1.85
                                      0.90
                                      0.77
                                      1.29
                                      0.95
                                   tall grass
                                      1.00
                                      0.85
                                      0.41
                                      0.35
                                      0.59
                                      0.44
                       broadleaf plants and small insects
                                      1.22
                                      1.04
                                      0.51
                                      0.43
                                      0.73
                                      0.54
                           fruits/pods/large insects
                                      0.14
                                      0.12
                                      0.06
                                      0.05
                                      0.08
                                      0.06
 [a]  The maximum application rate for watermelons and strawberries is 0.222 lbs a.i./A, with a 5-day application interval and 2 applications.
 [b] The maximum application rate for cherries is 0.092 lbs a.i./A, with a 5-day application interval and 2 applications. This scenario for cherries results in the lowest EECs from any of proposed application rates for any crop on the Fluopyram 500 SC label. All scenarios for terrestrial modeling use the maximum application rate for any given use pattern. Therefore, these numbers represent the exposure from the maximum application rate for the crop with the lowest proposed use rates of fluopyram.
 [c] The maximum aerial application rate for potatoes is 0.092 lbs a.i./A, with 5-day application interval and 3 applications. The aerial scenario for potatoes has the highest number of applications for any crop on the Fluopyram 500 SC label.
 Bolded values represent LOC exceedances (RQ >=1).

 Table 27.  Chronic mammalian dietary RQs estimated for fluopyram use scenarios with 35-day and 7.37-day foliar dissipation half-lives using upper-bound Kenaga values

                          Watermelons and Strawberries
                            max exposure scenario[a]
                                   Cherries
                            min exposure scenario[b]
                                    Potatoes
                scenario with highest number of applications[c]
                                  Forage Type

                                35-day half-life
                               7.37-day half-life
                                35-day half-life
                               7.37-day half-life
                                35-day half-life
                               7.37-day half-life
                                  short grass
                                      7.81
                                      6.66
                                      3.24
                                      2.76
                                      4.63
                                      3.42
                                   tall grass
                                      3.58
                                      3.05
                                      1.48
                                      1.26
                                      2.12
                                      1.57
                       broadleaf plants and small insects
                                      4.39
                                      3.75
                                      1.82
                                      1.55
                                      2.60
                                      1.93
                           fruits/pods/large insects
                                      0.49
                                      0.42
                                      0.20
                                      0.17
                                      0.29
                                      0.21
 a  The maximum application rate for watermelons and strawberries is 0.222 lbs a.i./A, with a 5-day application interval and 2 applications.
 [b] The maximum application rate for cherries is 0.092 lbs a.i./A, with a 5-day application interval and 2 applications. This scenario for cherries results in the lowest EECs from any of proposed application rates for any crop on the Fluopyram 500 SC label. All scenarios for terrestrial modeling use the maximum application rate for any given use pattern. Therefore, these numbers represent the exposure from the maximum application rate for the crop with the lowest proposed use rates of fluopyram.
 [c] The maximum aerial application rate for potatoes is 0.092 lbs a.i./A, with 5-day application interval and 3 applications. The aerial scenario for potatoes has the highest number of applications for any crop on the Fluopyram 500 SC label.
 Bolded values represent LOC exceedances (RQ >=1).

 		a.  Location of Wildlife Species

 For screening terrestrial risk assessments, a generic bird or mammal is assumed to occupy either the treated field or adjacent areas receiving the pesticide at a rate equivalent with the treatment rate on the target field.  This assumption may lead to an overestimation of exposure to species that do not occupy the treated field. The actual habitat requirements of any particular terrestrial species are not considered, and it is assumed that species occupy, exclusively and permanently, the treated area being modeled.  This assumption leads to a maximum level of exposure in the risk assessment.

 		b.  Routes of Exposure

 Dietary Exposure
 Screening-level risk assessments for spray applications of pesticides assume that 100% of the diet is relegated to single food types foraged only from treated fields. These assumptions are likely to be conservative for many species and will tend to overestimate potential risks. The assumption of 100% diet from a treated area may be realistic for acute exposures, but long-term exposures modeled as single food types composed entirely of material from a treated field is uncertain.

 Inhalation Exposure
 The screening risk assessment also considered acute inhalation exposure from spray material in droplet form at the time of application and vapor phase pesticide volatilizing from treated surfaces. Inputs for the STIR tool (version 1.0) included fluopyram's molecular weight (396.72 g/mole), vapor pressure (2.33 x 10[-8] mm Hg), maximum application rate (0.222 lbs a.i./acre), as well as available avian and mammalian toxicity information. Because no definitive endpoints were available for acute oral mammalian or avian studies, the highest concentration tested was used as an upper-bound estimate of acute toxicity (2000 mg a.i./kg bw for both mammals and birds). A 4-hour rat inhalation study was submitted for fluopyram (LC50 = 2.091 mg a.i./L). Due to the chemical's low vapor pressure, low acute oral toxicity to mammals and birds and low inhalation toxicity to mammals, acute inhalation exposure at the time of fluopyram application is not an appreciable route of exposure for mammals or birds.

 Dermal Exposure
 The screening assessment does not consider fluopyram dermal exposure to terrestrial organisms.
 The Agency is actively pursuing modeling techniques to account for dermal exposure via direct application of spray and by incidental contact with contaminated vegetation, soil and water.

 Drinking Water Exposure
 Drinking water exposure to a pesticide active ingredient may be the result of consumption of surface water or consumption of the pesticide in dew or other water on the surfaces of treated vegetation.  For pesticide active ingredients with a potential to dissolve in runoff, puddles on the treated field may contain the chemical. The SIP tool (version 1.0) was used to assess the potential for exposure concerns to birds and mammals via drinking water alone. Fluopyram's solubility in water (16 mg/L) and toxicity to avian and mammalian species are inputs for the potential upper-bound drinking water calculations. Because no definitive endpoints were available for acute oral mammalian or avian studies, the highest concentration tested was used as an upper-bound estimate of acute toxicity (2000 mg a.i./kg bw for both mammals and birds). Chronic NOAEL/NOAEC toxicity values were 15 mg a.i./kg bw for mammals and 46.7 mg a.i./kg diet for birds. Based on this information, fluopyram exposure through drinking water alone does not present an acute concern for mammals or birds or chronic concern for mammals. There is a potential chronic concern from drinking water exposure for birds.

       	c.  Incidental Pesticide Releases Associated with Use

 This risk assessment is based on the assumption that the entire treatment area is subject to fluopyram application at the rates specified on the label.  In reality, there is the potential for uneven application of fluopyram through such plausible incidents as changes in calibration of application equipment, spillage, and localized releases at specific areas of the treated field that are associated with specifics of the type of application equipment.

       	d.  Residue Levels Selection

 As discussed earlier in the exposure section of this document, the Agency relies on the work of Kenaga and Fletcher et al. (1994) for setting the assumed pesticide residues in wildlife dietary items. The Agency believes that these residue assumptions reflect a realistic upper-bound residue estimate for pesticides, with the assumption that these residues reflect a chemical-specific estimate for fluopyram.

       4.  Effects Assessment

 The data available to support the terrestrial and aquatic effects assessment for fluopyram is incomplete.  Data gaps, uncertainties and limitations are summarized as follows:

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