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

                          OFFICE OF CHEMICAL SAFETY
                           AND POLLUTION PREVENTION

Environmental Fate and Ecological Risk Assessment for Fenpyrazamine New Chemical Registration for Proposed Uses on Almonds, Pistachios, Lettuce, Strawberries, Bushberries, Caneberries, Ginseng, and Ornamentals

                                      \s
                        Chemical Formula:  C17H21N3O2S
                               PC Code:  090109
                           CAS Number:  473798-59-3

Prepared by:
Gabe Rothman, Environmental Scientist
Justin Housenger, Biologist

Reviewed by:
José Melendez, Chemist
Al Vaughan, Risk Assessment Project Leader, ERB5
Mah Shamim, Ph.D., Branch Chief, ERB5

                                  United States Environmental Protection Agency
                                                   Office of Pesticide Programs
                                        Environmental Fate and Effects Division
                                                    Environmental Risk Branch V
                                                         1200 Pennsylvania Ave.
                                                               Mail Code 7507P
                                                         Washington, D.C. 20460

                               Table of Contents

1.	Executive Summary	5
1.1	Nature of Chemical Stressor	5
1.2	Potential Risks to Non-target Organisms	6
1.2.1	Aquatic Animals and Plants	6
1.2.2	Terrestrial Animals and Plants	7
1.3	Risk Characterization	8
2.	USE CHARACTERIZATION	8
3.	ENVIRONMENTAL FATE AND TRANSPORT CHARACTERIZATION	9
4.	ECOLOGICAL TOXICITY CHARACTERIZATION	20
4.1	Receptors	20
4.2	Ecosystems at Risk	21
4.3	Assessment Endpoints	22
4.4	Ecological Effects Characterization	22
4.4.1	Aquatic Effects	23
*	Freshwater Fish	31
*	Freshwater Invertebrates	32
*	Estuarine/Marine Fish	33
*	Estuarine/Marine Invertebrates	34
*	Benthic (Sediment Dwelling) Invertebrates	35
*	Vascular and Non-vascular Aquatic Plants	36
4.4.2	Terrestrial Effects	38
*	Birds (Acute Toxicity)	42
*	Birds (Chronic Toxicity)	42
*	Mammals (acute toxicity)	43
*	Mammals (chronic toxicity)	43
*	Non-target Beneficial Insects	44
*	Other Non-target Terrestrial Organisms	44
*	Terrestrial Plants	45
5.	PROBLEM FORMULATION	46
5.1	Risk Hypotheses	46
5.2	Conceptual Model	47
5.3	Analysis Plan	48
5.3.1	Measures of Exposure	48
5.3.2	Measures of Effects	49
5.3.3	Integration of Exposure and Effects	49
6.	EXPOSURE ANALYSIS	50
7.	RISK CHARACTERIZATION	60
7.1	Risk Estimation - Integration of Exposure and Effects Data	60
7.1.1	Non-target Aquatic Animals and Plants	60
a.	Water Column Exposure: Acute and Chronic Risk to Animals	61
b.	Sediment Exposure: Chronic Risk to Benthic Invertebrates	64
c.	Aquatic Plants	67
7.1.2	Non-target Terrestrial Animals	69
a.	Acute and Chronic Risk to Birds	69
b.	Acute and Chronic Risk to Mammals	70
c.	Non-target Beneficial Insects	72
d.	Risks to Terrestrial Plants	73
7.2	Risk Description	74
7.2.1	Risks to Aquatic Animals	74
a.	Potential for Acutely Toxic Exposures	74
b.	Potential for Chronically Toxic Exposures	75
7.2.2	Risks to Terrestrial Animals	79
a.	Potential for Acutely Toxic Exposures	79
b.	Potential for Chronically Toxic Exposures	80
7.2.3	Risks to Terrestrial Plants	81
7.2.4	Review of Incident Data	81
7.2.5	Threatened and Endangered Species Concerns	81
7.2.6	Description of Assumptions, Limitations, Uncertainties, Strengths and Data Gaps	83
a.	Incidental Pesticide Releases Associated with Use	83
b.	Exposure for Aquatic Species	83
c.	Exposure for Terrestrial Species	86
d.	Effects Assessment	86
*	Age Class and Sensitivity of Effects Thresholds	87
*	Lack of Effects Data for Amphibians and Reptiles	87
*	Use of the Most Sensitive Species Tested	88
8.	IDENTIFICATION OF DATA GAPS	88
9.	REFERENCES	89
*	Environmental Fate Studies	89
*	Ecological Effects Studies	91
Open Literature and Government Reports	96

                                  Appendices

Appendix A.  The Risk Quotient Method and Levels of Concern
Appendix B.  Output of STIR Results
Appendix C.  Output of SIP Results
Appendix D.  Output of TerrPlant Results
Appendix E.  Sample PRZM/EXAMS Input and Output Files
Appendix F.  Formation of Fenpyrazamine Transformation Products in Environmental Fate Studies.
Appendix G.  Toxicity Comparisons of Fenpyrazamine and Transformation Products

                               Table of Figures

Figure 1.  Proposed degradation and dissipation pathways in soil.	15
Figure 2.  Proposed degradation and dissipation pathways in water.	17

                                Table of Tables

Table 1.  Summary use information for fenpyrazamine, based on the proposed V-10135 4 SC Fungicide suspension concentrate label by Valent U.S.A.	9
Table 2.  Physical and chemical properties of fenpyrazamine.	10
Table 3.  Summary of fenpyrazamine environmental fate properties.	10
Table 4.  Comparison of physical chemical properties of fenpyrazamine transformation products to parent fenpyrazamine.	18
Table 5.  Taxonomic groups and test species evaluated for ecological effects in this screening-level risk assessment	20
Table 6.  Toxicity endpoints used in risk quotient calculations.	21
Table 7.  Toxicity reference values for aquatic organisms exposed to fenpyrazamine.	23
Table 8.  Toxicity Reference Values For Aquatic Organisms Exposed to Degradation Products of Fenpyrazamine.	30
Table 9.  Toxicity Reference Values For Terrestrial Organisms Exposed To Fenpyrazamine.	38
Table 10.  Summary of PRZM/EXAMS input parameter values for physical chemical and fate properties used for fenpyrazamine surface water aquatic EECs.	50
Table 11.  Crop management PRZM/EXAMS inputs used in aquatic exposure modeling.	52
Table 12.  PRZM/EXAMS estimated one-in-ten year upper bound concentrations in surface water (ppb) for aerial applications of fenpyrazamine.	54
Table 13.  PRZM/EXAMS estimated one-in-ten year upper bound concentrations in surface water (ppb) for ground applications of fenpyrazamine.	55
Table 14.  PRZM/EXAMS estimated one-in-ten year upper bound concentrations in benthic pore water (ppb) for aerial applications of fenpyrazamine.	55
Table 15.  PRZM/EXAMS estimated one-in-ten year upper bound concentrations in benthic pore water (ppb) for ground applications of fenpyrazamine.	56
Table 16. PRZM/EXAMS estimated one-in-ten year upper bound concentrations in sediment (mg fenpyrazamine/kg sediment, dry weight) for aerial applications of fenpyrazamine.	56
Table 17.  PRZM/EXAMS estimated one-in-ten year upper bound concentrations in sediment (mg fenpyrazamine/kg sediment, dry weight) for ground applications of fenpyrazamine.	57
Table 18.  Terrestrial food item residue estimates for birds with proposed fenpyrazamine uses on various crops.	58
Table 19.  Terrestrial food item residue estimates for mammals with proposed fenpyrazamine uses on various crops.	58
Table 20.  TerrPlant derived EECs for dry and semi-aquatic areas resulting from proposed fenpyrazamine uses.	59
Table 21.  Acute and chronic RQs for evaluating risk of fenpyrazamine exposure to freshwater and estuarine/marine fish.	62
Table 22.  Acute and chronic RQs for evaluating risk of fenpyrazamine exposure to freshwater and estuarine/marine invertebrates.	63
Table 23.  Chronic RQs for risk of fenpyrazamine exposure to freshwater benthic invertebrates[1,2].	65
Table 24.  Chronic RQs for risk of fenpyrazamine exposure to estuarine/marine benthic invertebrates[1,2,3].	66
Table 25.  RQs for evaluating toxic risk of fenpyrazamine exposure to vascular and non-vascular aquatic plants.	67
Table 26.  Dose-based RQs for birds due to exposure to proposed uses of fenpyrazamine.	69
Table 27.  Dietary-based RQs for birds due to exposure to proposed uses of fenpyrazamine.	70
Table 28.  Acute dose-based RQs for mammals due to exposure to proposed uses of fenpyrazamine.	71
Table 29.  Chronic dose-based RQs for mammals from exposure to proposed uses of fenpyrazamine.	71
Table 30.  Chronic dietary-based RQs for mammals due to exposure to proposed uses of fenpyrazamine.	72
Table 31.  RQs for terrestrial plants resulting from the propose uses of fenpyrazamine.	73

   1. Executive Summary

This ecological risk assessment addresses the new active ingredient fenpyrazamine which is proposed to be used in conventional ground and aerial foliar applications on almonds, grapes, lettuce, and strawberries as major food uses as well as on ornamentals as the only major non-food use.  Additional IR-4 minor crop uses proposed for fenpyrazamine are conventional ground and aerial foliar applications on pistachio, bushberry, caneberry, and ginseng crops.  Proposed maximum application rates of fenpyrazamine on crops range between 0.375 lbs. a.i./A  -  1.089 lbs. a.i./A with three to four retreatment intervals at a minimum of 7 seven days between applications specified on the draft product label.

         1.1 Nature of Chemical Stressor

The subject chemical addressed in this ecological risk assessment is identified by the chemical fenpyrazamine (PC Code 090109) with the chemical synthesis (IUPAC) name of S-allyl 5-amino-2,3-dihydro-2-isopropyl-3-oxo-4-(o-tolyl)pyrazole-1-carbothiaote.  Fenpyrazamine is a pyrazole fungicide intended to control a number of fungal diseases including brown rot, green fruit rot/jacket rot, botrytis bunch rot, lettuce drop, gray mold, and botrytis blight gray mold.   Fenpyrazamine's mode of action has not been fully elucidated, but it is thought to inhibit the generation of reproductive spores via inhibition of the germ tube and mycelium elongation.  In addition, pyrazole fungicides are known to inhibit the succinate-dehydrogenase enzyme which serves a critical mechanism as part of the citric acid cycle and providing a pathway for electronic transfer throughout the organism.  The trade name for this compound is V-10135 4 SC Fungicide (a suspension concentrate).  The labeled formulation contains 43.6 percent of the active ingredient fenpyrazamine and 56.4 percent inert ingredients.

Fenpyrazamine foliar applications using ground and aerial sprays may impact aquatic habitats within water bodies and ground water given that it possesses similar physical chemical properties and persistence as other chemicals which are known to translocate to these media.  In addition, fenpyrazamine applications potentially result in dietary exposure and exposure to plants in the terrestrial environment given its moderate to high persistence in the environment.  Fenpyrazamine is moderately persistent in alkaline aerobic soil with half lives ranging between 38 and 49 days.  However, fenpyrazamine degrades much slower in acidic aerobic soil, with half-lives between 201  -  801 days.  In anaerobic acidic soil environments, half-lives are a little less at 128 days.  Once reaching the water column, fenpyrazamine is moderately persistent to persistent, especially in acidic environments, with half-lives ranging from 12 days  -  280 days under aerobic and anaerobic conditions.  Fenpyrazamine's rapid hydrolysis at pH9 (with a half-life of 12 days) and high stability at pH5 suggests that hydrolysis may mediate fenpyrazamine's degradation in the environment.  Fenpyrazamine (S-2188) degrades mainly to S-2188-OH, S-2188-DC, and MCNI in soil and water.  However, submitted ecotoxicity toxicity data as well as structural activity relationships (ECOSAR v.1.0) indicates that fenpyrazamine is at least an order of magnitude or more toxic than these degradates depending on the taxa.  Therefore, fenpyrazamine is considered the primary stressor in this risk assessment.  Further information related to the justification of fenpyrazamine as the primary stressor is provided in Section 5.2.

         1.2 Potential Risks to Non-target Organisms

This is the Environmental Fate and Effects Division's (EFED) national screening-level ecological risk assessment for the proposed registration of fenpyrazamine.  A summary of the major conclusions and uncertainties of this assessment for aquatic and terrestrial receptors respectively is included below.

                 1.2.1 Aquatic Animals and Plants

 Acute Risk Concerns: The results of this screening-level risk assessment suggest minimal acute risk of acute toxicity to freshwater and estuarine/marine fish and freshwater invertebrates based on runoff and spray drift from foliar applications to adjacent surface waters.  There were no LOC exceedances for these three taxa.  There was acute risk indicated to listed species and risks that could be mitigated by restricted use for estuarine/marine invertebrates from the proposed uses on ginseng and ornamentals.
 Chronic Risk Concerns: Chronic risks to freshwater fish and aquatic (freshwater and estuarine/marine) invertebrates were below the Agency's chronic LOCs for all proposed uses of fenpyrazamine.  Chronic risks to estuarine/marine fish could not be determined with precision due to a non-definitive NOAEC (< 39 ug a.i/L).  Despite the lack of bonded estimation of chronic risk for estuarine/marine fish, (i.e., RQ values preceded by ">") the LOC of 1 was exceeded for the proposed uses on ornamentals and ginseng.  However there is uncertainty with this and the remaining chronic RQ values for estuarine/marine fish as it is not known how far above the estimated RQ that the actual RQ falls.  A similar case exists with estuarine/marine invertebrates (NOAEC of 98 ug a.i/L).  However in this case, the RQ would be preceded by "<" values to indicate that the estimated RQ is an "at most," scenario.  For both freshwater and estuarine/marine invertebrates, there were no exceedances of the chronic LOC for any of the proposed uses of fenpyrazamine.

 Risks to Aquatic Plants: Based on the available data to one vascular and 4 non-vascular aquatic plant species, risks to aquatic plants are indicated for non-vascular plants but not for vascular plants.  Toxicity data indicated that the most sensitive non-vascular aquatic plant was 2 orders of magnitude more sensitive than vascular aquatic plants which led to the listed LOC being exceeded for all uses of fenpyrazamine and to non-listed LOCs being exceeded for all uses except almonds and pistachios for non-vascular plants.  There were no non-listed or listed LOC exceedances for vascular aquatic plants for all proposed uses of fenpyrazamine.

 Risks to Benthic Invertebrates:  Chronic data are available for 3 species of freshwater and estuarine/marine benthic invertebrates.  However, the chronic RQs could not be estimated with precision due to non-definitive endpoints being reached for the most sensitive freshwater and estuarine/marine benthic invertebrate endpoints (NOAECs of <101 and <3000 ug a.i/kg sediment, respectively).  Using the chronic LOC of 1 and the 1-in-10 year 21-day average EECs for risk estimation purposes, sediment RQs exceeded the LOC for freshwater benthic invertebrates for the proposed uses on ornamentals and ginseng.  Corresponding pore water EECs also exceeded the LOC for the ornamental and ginseng uses.  For estuarine/marine benthic invertebrates, there was no sediment or pore water RQs that exceeded the LOC.  As was the case for chronic risk to estuarine/marine fish, there is uncertainty with these chronic RQ values as it is not known how far above the estimated RQ that the actual RQ falls.

                 1.2.1 Terrestrial Animals and Plants

 Acute Risks Concerns for Birds and Mammals:  Acute dose-based risks for birds were indicated for small birds eating short grass for all proposed uses of fenpyrazamine.  There were other LOC exceedances for additional food items and size class of organisms depending on the use.  The acute high risk LOC of 0.5 was exceeded only in the case of small birds eating short grass for the ornamental use.  Other LOC exceedances were the acute endangered species LOC (0.1) and the acute restricted use LOC (0.2).  There were no acute dietary based exceedances for birds except a marginal exceedance of the acute endangered species LOC for dietary ingestion of short grass under the ornamental use.  Acute dose-based risks for mammals indicated marginal exceedances of the acute endangered species LOC (0.1) for small and medium sized mammals ingesting short grass under the ornamental use.

 Chronic Risk Concerns for Birds and Mammals:  A potential for chronic risks to birds and mammals was indicated in this assessment via dietary-based exposure.  Exceedances of the chronic LOC of 1 were indicated for all proposed uses of fenpyrazamine except the uses on almonds and pistachios for at least one food item.  Chronic dose-based RQs for mammals indicate exceedances of the LOC for small and medium sized mammals exposed to at least one food item for all proposed uses and exceedances for all three size classes for the ornamental use only.  There were no chronic dietary-based RQ exceedances for any of the proposed uses.

 Risk Concerns for Terrestrial Plants:  For almonds and pistachios, the acute LOC of 1 was exceeded for listed dicot species in semi aquatic areas.  There were no other LOC exceedances for this use.  For lettuce, grapes, bushberries, caneberries, strawberries, and ginseng, the acute LOC of 1 was exceeded for listed dicot species in semi aquatic areas with no other LOC exceedances.  For the use on ornamentals, listed monocot species in semi aquatic areas and listed dicot areas in dry, semi aquatic, and areas resulting from spray drift all exceeded the acute LOC.  Therefore, the potential for risk is indicated to these groups of terrestrial plants from the uses exceeding the LOC of 1.

 It is important to note that the RQs summarized in Table 32 did not have EC25 endpoints input into the TerrPlant model for vegetative vigor on account of a lack of a 25% or greater inhibition for all variables for these studies precluding that endpoint to be estimated.  Furthermore, the NOAEC for seedling emergence for dicot species was a non-definitive endpoint (<0.035 lbs a.i/A).  Additionally, the EC25 values for seedling emergence (monocot and dicot) were non definitive (>1.54 ad >0.53 for monocots and dicots, respectively).  Therefore the RQs are not determined to be precise, and there exists uncertainty with these endpoints that arise from the use of non-definitive RQs.

Risk Concerns for Beneficial Insects: Available toxicity data for fenpyrazamine indicate it is practically non-toxic to honeybee on an acute contact and an acute oral basis.  While exposure potential exists via pathways such as spray drift, limited data available show fenpyrazamine to be of limited toxicity to the honey bee.  	Additionally, an acute toxicity study to the earthworm indicated that survival ranged from 92.5 to 100%, depending on the treatment concentration.  The LC50 was determined to be >800 mg a.i/kg dw soil and therefore the data (while limited) suggest fenpyrazamine to be of low toxicity to the earthworm.

         1.2 Risk Characterization

In characterizing the risk to terrestrial and aquatic organisms exposed to fenpyrazamine, the largest uncertainties in the currently submitted registrant data is the absence of environmentally-relevant hydrolysis data at pH7 and availability of data in only one water-sediment system anaerobic aquatic metabolism study.  .  Therefore, to address these deficiencies, conservative assumptions are made within the PRZM/EXAMS model that lead to high estimates of the 1-in-10 year 21-day and 60-day average EECs in water and sediment that are evidenced by relatively modest decreases from their peak values.  This translates into more conservative estimates of chronic risk to aquatic organisms inhabiting both the water column and the benthic zone.  The taxa that are implicated the most by these conservative estimates of chronic exposure are estuarine/marine fish and freshwater and estuarine/marine sediment invertebrates.  Registrant submitted data for these three taxa yielded non-definitive (i.e. "<") NOAECs and therefore the estimated RQ is only a lower bound estimate of risk (i.e. ">").  It is an uncertainty of how much higher than the estimated lower bound RQ that the actual unbounded RQ falls but more refined estimates of chronic exposure would likely mitigate some of this uncertainty by driving the current unbounded estimates of chronic risk further down away from the chronic LOC.

         2. USE CHARACTERIZATION

V-10135 4 SC Fungicide (43.6 percent fenpyrazamine a.i., 56.4% inert ingredients) suspension concentrate is being proposed for aerial and ground foliar applications on almonds, grapes, lettuce, and strawberries for major food crop uses as well as on ornamentals (greenhouse and nursery) as the only major non-food crop use.  Additional IR-4 minor crop uses are proposed for conventional ground and aerial foliar applications on pistachio, bushberry, caneberry, and ginseng crops.  Proposed maximum application rates of fenpyrazamine range between 0.375 lbs. a.i./A  -  1.089 lbs. a.i./A with three to four treatments, at a minimum of 7 seven days between applications specified on the proposed product label.  Table 1 summarizes the labeling for the proposed uses of fenpyrazamine.

Table 1.  Summary use information for fenpyrazamine, based on the proposed V-10135 4 SC Fungicide suspension concentrate label by Valent U.S.A.
                                   CROP USE
                               REGULATORY ACTION
                          MAX. SINGLE APP. RATE
                                 (lbs. a.i./A)
              MAX. NUMBER OF APPS. and MIN. RETREATMENT INTERVAL
                              SEASONAL APP. RATE
                               (lbs. a.i./A) [5]
                             APPLICATION METHOD 2
                                    Almonds
                                    Sec. 3
                                     0.375
                             3 apps., 7 days apart
                                     1.125
                                     G, A
                                    Grapes
                                    Sec. 3
                                      0.5
                             3 apps., 7 days apart
                                      1.5
                                     G, A
                                    Lettuce

                                 Strawberries
                                    Sec. 3
                                      0.5
                             4 apps., 7 days apart
                                      2.0
                                     G, A
                                  Ornamentals
                                    Sec. 3
                                   1.089[1]
                             3 apps., 7 days apart
                                     3.267
                                     G, A
                                  Pistachios
                                     IR-4
                                     0.375
                             3 apps., 7 days apart
                                     1.125
                                     G, A
                                Bushberries[3]
                                     IR-4
                                      0.5
                             3 apps., 7 days apart
                                      1.5
                                     G, A
                                Caneberries[4]

                                      *
                                    Ginseng
                                     IR-4
                                      0.5
                             4 apps., 7 days apart
                                      2.0
                                     G, A
[1.] Maximum application rate based on a rate of 0.5lbs./100 gal specified on the label.  According to the label, 100 gallons of spray solution treats 20,000 square feet.  Therefore, 0.5 lbs./20,000 ft.[2] is equivalent to 1.089 lbs./A.
[2]	Application method identifiers:  G = Foliar ground spray/spray chemigation; A = Foliar Aerial Spray
[3]	Bushberries include aronia berry, blueberry, highbush and lowbush, buffalo currant, Chilean guava, cranberry, highbush, black currant, red currant, elderberry, European barberry, gooseberry, edible honeysuckle, huckleberry, jostaberry, juneberry, lingonberry, native currant, salal, sea buckthorn, and cultivars.
[4]	Caneberries include blackberry, logan berry, raspberry, wild raspberry, and cultivars.
[5]	Seasonal application rate specified on label except for ornamentals.  Seasonal application rate for ornamentals assumed based on maximum number or applications specified on label.

         3. ENVIRONMENTAL FATE AND TRANSPORT CHARACTERIZATION

Physical and chemical properties of fenpyrazamine are shown in Table 2 below.  Environmental fate and transport properties of fenpyrazamine based upon registrant submitted studies or other references are shown in Table 3 below.  Since fenpyrazamine is moderately mobile and soluble, fenpyrazamine applied to crops has the capability of being translocated to nearby water bodies via residues dissolving in runoff water.  In addition, fenpyrazamine may also sorb to soil and therefore may reach nearby water bodies via erosion.  Hydrolysis appears to mediate the overall degradation of fenpyrazamine in soil and water as it declines faster in alkaline environments rather than acidic environments.

Table 2.  Physical and chemical properties of fenpyrazamine.
                                   Property
                                Value and units
                                MRID or Source
                                   Structure
                                      \s
                                 MRID 48399915
                                Chemical Class
                        Pyrazole Carboxamide Fungicide
                            http://www.alanwood.net
                               Chemical Formula
                                  C17H21N3O2S
                                 MRID 48399915
                               Molecular Weight
                                  331.4 g/mol
                                 MRID 48399915
                                Vapor Pressure
                                    (25°C)
                             2.17 x 10[-][10] torr
                                 MRID 48399916
                          Henry's Law Constant [1]
                        2.28 x 10[-][10] atm·m[3]/mol
                                   EpiSuite
                               HENRYWIN v. 3.20
                               Water Solubility
                                 (pH 7, 20°C)
                                   20.4 mg/L
                                 MRID 48399915
                   Octanol  -  water partition coefficient
                                   (log KOW)
                                     3.52
                                 MRID 48399914

Table 3.  Summary of fenpyrazamine environmental fate properties.

                          Study/ OCSPP Guideline No.

                                Value and unit

                              MRID # or Citation

                         Study Classification, Comment
                              Abiotic Hydrolysis

                                  (835.2120)

pH4:  Stable (Low levels of degradation observed)
pH7:  Environmentally relevant half-lives could not be determined, but qualitative useful information was obtained.
pH9:  10.9 days

                                   48399923
                                 Supplemental

Data for pH7, 25°C not provided

Degradates observed:  S-2188-OH at pH 4, pH7, and pH9; and S-2188-DC at pH7 and pH9.
                              Aqueous Photolysis

                                  (835.2240)
t (1/2) = 1.64 days (SFO)
pH 6.90  -  6.96 (neutral)
                                   48399924
                                  Acceptable

Environmentally relevant half-life, corrected for dark control

Complete formation and decline of degradates could not be established

                                Soil Photolysis

                                  (835.2410)
UK SiL (alkaline, pH 6.9):  t (1/2)   81.05 days (SFO)

                                   48399926

                                 Supplemental

Data showing representativeness of foreign soil to domestic soil (e.g., taxonomic classification) not provided

Environmentally relevant half-life, corrected for dark control

                              Degradation in air

                                  (835.2370)
Reaction with Hydroxyl Radicals
t (1/2) = 0.102 days

Reaction with Ozone
t (1/2) = 0.347 days
                                   EpiSuite
                                AopWin v. 1.92
                               Estimated values
                            Aerobic Soil Metabolism

                                  (835.4100)
UK SL (alkaline, pH 7.5):  t (1/2) = 49.3 days (DFOP)
UK SL (acidic, pH 5.2):  t (1/2) = 801 days (IORE)
UK L (alkaline, pH 7.9):  t (1/2) = 37.7 days (IORE)
UK SiL (acidic, pH 6.9):  t (1/2) = 230 days (DFOP)

NJ SiL (acidic, pH 6.3):  t (1/2) = 201 days (IORE)

                                   48399920

                                   48399927

                                  Supplemental

Data showing representativeness of foreign soil to domestic soil (e.g., taxonomic classification) not provided

                                 Supplemental

Soil moisture levels throughout study not reported
                           Anaerobic Soil Metabolism

                                  (835.4200)
NJ SiL (acidic, pH 6.8):  t (1/2) = 128 days (SFO)
                                   48399928
                                  Acceptable

Complete formation and decline of degradates could not be established

                          Aerobic Aquatic Metabolism

                                  (835.4300)
UK Silty Clay Loam Sediment:  t (1/2) = 18.9 days (SFO)
(alkaline water pH7.3  -  8.0, acidic sediment pH 6.5  -  6.6 )
Swiss Lake Sand Sediment: :  t (1/2) = 280 days (IORE)	 (acidic water pH 6.0  -  6.36, alkaline sediment pH 7.5)
                                   48399929
                                 Acceptable[4]

pH initial values in study

Complete formation and decline of degradates could not be established

                         Anaerobic Aquatic Metabolism

                                  (835.4400)
MS Clay Sediment:  t (1/2) = 12.2 days (SFO)
(alkaline water, pH 8.3, acidic sediment pH 6.9,
                                   48399930
                                 Acceptable[5]

pH initial values in study

Complete formation and decline of degradates could not be established

                    Mobility, unaged leaching, adsorption/
                                  desorption

                                  (835.1220)
UK CL:  Koc = 250 mL/g; Kd = 8.7 mL/g;
	OC = 4.8%; pH8.0
UK SiL:  Koc = 343 mL/g; Kd = 7.4 mL/g;
	OC = 2.7%; pH7.0
UK L:  Koc = 123 mL/g; Kd = 4.2 mL/g;
	OC = 3.8%; pH6.0
UK LS:  Koc = 766 mL/g; Kd = 5.7 mL/g ;
	OC = 0.8 %; pH5.1
Japan SL:  Koc =269 mL/g; Kd = 6.6 mL/g ;
	OC = 3.2 %; pH5.9

NJ SiL:  Koc = 366 mL/g;  Kd = 3.5 mL/g ;
	OC = 1.4%; pH6.3
CA LS:  Koc = 585 mL/g; Kd = 0.87 mL/g ;
	OC = 0.2%; pH7.5

                                   48399919

                                   48399922

                                 Supplemental

Data showing representativeness of foreign soil to domestic soil (e.g., taxonomic classification) not provided

                                 Supplemental

Only 4 test concentrations used in study
                         Terrestrial Field Dissipation

                                  (835.6100)
CA SL (neutral, pH 6.4  -  7.1):  t (1/2) = 9.68 days (IORE)
CA LS (neutral, pH 5.7 -7.3):  t (1/2) = 7.68 days (IORE)
ID L (neutral, pH 6.7  -  7.7):  t (1/2) = 7.30 days (IORE)
NY S (neutral, pH 6.4  -  6.7):  t (1/2) = 24.3 days (IORE)
                                   48399931
                                   48399932
                                   48399933
                                   48399934
                                  Acceptable
                                  Acceptable
                                  Acceptable
                                  Acceptable
                                Fish Bioconcen
                             -tration Factor (BCF)

                                  (850.1730)
Bluegill Sunfish Edible Tissues
Steady State BCF = 7 L/kg
Fenpyrazamine accounted for <1 percent of total radioactive residues after a depuration period of 14 days.
Bluegill Sunfish Non-Edible Tissues
Steady State BCF = 10 L/kg
Fenpyrazamine accounted for <1 percent of total radioactive residues during depuration phase.
Bluegill Sunfish Whole Fish Tissues
Steady State BCF = 9 L/kg
Fenpyrazamine accounted for <1 percent of total radioactive residues during depuration phase.
                                   48400005
                                  Acceptable
                                     Env.
                                   Chemistry
                                    Method
                                     (ECM)
                             Water (Tap and Pond)
                    Mean Recoveries 85  -  93%; RSD 4 - 11

                                 Water (Well)
               Mean Recoveries 81.2  -  102%; RSD 3.53  -  18.8

                                     Soil
                    Mean Recoveries:  87%; RSD 2.3  -  2.9
                                   48399918

                                   48400034

                                   48400026

                                  Acceptable
                                  Independent
                                  Laboratory
                                  Validation
                                     (ILV)
                                 Water (Well)
               Mean Recoveries 103  -  94.6%; RSD 2.34  -  2.62

                                     Soil
                Mean Recoveries:  89.4% -90.9%; RSD 6.5  -  8.4
                                   48400034

                                   48400026

                                  Acceptable
                               Storage Stability
                                     Soil

                      Normalized/Corrected Mean Recovery:
                    100  -  122.1 percent (Days 0  -  366)

                                   48399921
                                  Acceptable
[1]  NA means not applicable.
[2]  Half life degradation kinetics scheme determinations:
 SFO = Single First Order, IORE = Indeterminate Order Rate Equation, DFOP = Double First Order in Parallel
Kinetic models and representative half-lives were determined in agreement with the "Guidance for Evaluating and Calculating Degradation Kinetics in Environmental Media" (2011), accessed 09/27/12 at http://www.epa.gov/oppfead1/international/naftatwg/guidance/guidance.htm .
3  Soil textural classifications:
	S:  Sand
	SL:  Sandy Loam
	LS:  Loamy Sand
	SiL:  Silt Loam
	L:  Loam
      CL: Clay Loam
4  Although the study is acceptable, there are still uncertainties related to the variations in biodegradation versus possible mediation from hydrolysis that is evident from the data.  Please refer to the uncertainties and limitations section at the end of this chapter, Section 7.2.6.b, and Section 8 for further details.
5  Although the study is acceptable, there is still a data gap since only one water-sediment system was evaluated.  Please refer to the uncertainties and limitations section at the end of this chapter, Section 7.2.6.b, and Section 8 for further details.

   * Fenpyrazamine Mobility and Transport to Water Bodies

Given foliar applications of fenpyrazamine, residues may be deposited into soil via washoff from rainfall or irrigation activities as well as directly deposited onto soil during the application.  Fenpyrazamine may reach surface water bodies or ground water given its solubility of 20.4 mg/L at 20°C (indicating that fenpyrazamine is highly soluble) (MRID No. 48399915) and Kd values ranging between 0.87  - 8.7 mL/g (indicating that fenpyrazamine is slightly to moderately mobile in soil)(MRID Nos. 48399919 and 48399922). It appears that sorption of fenpyrazamine is not well correlated to organic carbon content given the weak relationship between soil-water partition coefficients and organic carbon content collectively among soils.  Fenpyrazamine's properties are common to other pesticides that are known to dissolve in runoff water to reach surface water bodies and leach to ground water.  Furthermore, fenpyrazamine residues may also reach surface water bodies via erosion as its range of Kd values suggests that residues may bind to soil particles to a certain extent.  Fenpyrazamine is not expected to escape from dry or moist soil surfaces or water bodies to the air via volatilization given its low vapor pressure value of 2.17 x 10[-10] torr (at 25°C) (MRID No. 4833906) and low Henry's Law Constant of 2.28 x 10[-10] atm·m[3]/mol (at 25°C) (EpiSuite HENRYWIN v. 3.20).

   * Degradation of Fenpyrazamine (S-2188) and Identification of Transformation Products in Soil

Fenpyrazamine appears to be moderately persistent in alkaline soil environments.  Aerobic soil metabolism half-lives range between 37.7 and 49.3 days, respectively under alkaline conditions (MRID No. 48399920).  Although no sterile controls were included, it is expected that the biodegradation is supplemented by hydrolysis in alkaline environments.  These half-lives are most similar to the decline (e.g., runoff, leaching, and biodegradation) of fenpyrazamine observed in terrestrial field dissipation studies conducted in neutral soils in California (2 sites), Idaho (1 site), and New York (1 site) with total soil profile (including depths below the runoff extraction zone) half lives observed between 7.3 and 24.1 days (MRID Nos. 48399931, 48399932, 48399933, and 48399934).  Fenpyrazamine appears to be persistent in acidic soils with half-lives between 201  -  801 days as observed in aerobic soil metabolism studies (MRID Nos. 48399920, and 48399927)  In anaerobic acidic soil environments, half-lives are a little less at 128 days in NJ Silt Loam Soil (MRID No. 48399928).  There are no studies available for anaerobic soil alkaline environments.  There are also no field dissipation studies conducted in acidic environments.  Soil photolysis appears to be a minor degradation pathway with a half-life of 104 day in NJ Silt Loam Soil (MRID No. 48399926).

In alkaline aerobic soil metabolism studies (MRID No. 48399920)[5], the degradate S-2188-OH forms at levels of between 0.8 percent  -  2.7 percent of applied radioactivity (See Appendix F for a more detailed summarization of the degradates formed, their structures and at what percentages result).  For alkaline conditions, the degradate S-2188-DC forms at levels between 0.5  -  2.8 percent of applied radioactivity in aerobic soil metabolism studies (MRID Nos. 48399920 and 48399923).  In general, degradates were not observed to form to significant levels in the aerobic soil metabolism studies.   The likely mechanism of dissipation is due to incorporation into soil organic matter as evidenced by large levels of unextracted residues, accounting for approximately up to 70 percent of the material balance in two alkaline soils in aerobic soil metabolism studies (MRID No. 48399920)[5][,].  The identity of the unextracted residues (whether they consist of parent or metabolite residues) is not certain since both parent and degradates are moderately mobile as evident from partition coefficients shown ahead in Table 4.  Furthermore, the Koc values of degradates range between 123  -  1,704 mL/g, indicating a moderate tendency for residues to partition to soil much like fenpyrazamine.  It is not expected that unextracted residues incorporated in eroded soil layers which become sediment in water bodies will desorb into the water column as demonstrated by the exhaustive extraction procedures used in the laboratory studies.  This tendency has also been observed in the batch equilibrium studies (MRID No. 48399919) as less than 32 percent of residues were observed to desorb into the water column for all soils evaluated.

Based upon the information described above from the environmental fate laboratory studies, the degradation pathway for the terrestrial (soil) environment is presented in Figure 1 below.

Incorporated Residues to Soil Layer

Figure 1.  Proposed degradation and dissipation pathways in soil.

   * Degradation of Fenpyrazamine (S-2188) and Identification of Transformation Products in Water

Upon reaching water bodies, aqueous photolysis is expected to be the main degradation mechanism for fenpyrazamine in reservoir surface waters, with a half-life of 1.64 days (corrected for environmentally relevant conditions).  The degradates S-2188-DC and MCNI formed to significant levels of 65.6 and 19.9 percent of the applied, respectively.  Hydrolysis is also expected to be a key degradation pathway particularly in alkaline environments.  However, some degradation is evident in acidic, neutral, and alkaline environments with formation of the degradate S-2188-OH observed at pH4, pH7, and pH9; and S-2188-DC observed at pH7 and pH9.  An environmentally relevant hydrolysis half-lives of 10.9 days has been determined at pH9.  Fenpyrazamine is stable at pH4, although a very small amount of the degradate S-2188-OH was detected.  No environmentally relevant half-life at pH7 is available.  This deficiency is described in Table 3 and in the Uncertainties and Limitations section before the conclusion of this chapter.

Fenpyrazamine degrades at a moderate rate in aerobic alkaline environments with a half life of 18.9 days as indicated in an alkaline aerobic aquatic metabolism study for the Calwich Abbey, UK lake water- silty clay loam sediment system (MRID No. 48399929).  Although no sterile controls were included, it is expected that the biodegradation is supplemented by hydrolysis in alkaline environments.  In aerobic aquatic acidic environments, fenpyrazamine degrades much slower with a half life of 280 days in a Swiss lake  -  sand sediment system (MRID No. 48399929).  In anaerobic acidic aquatic environments, fenpyrazamine is moderately persistent with a half-life of 12.2 days in a Mississippi Creek  - clay sediment system (MRID No. 48399930).

In aerobic alkaline aquatic environments, the S-2188-OH and S-2188-DC degradates form in significant quantities encompassing up to 17.3 and 23.5 percent of the applied, respectively, in the Calwich Abbey, UK Lake  -  silty clay loam sediment system (MRID No. 48399929).  Like for aerobic soils, there are significant quantities of unextractable residues observed.  Unextracted residues in the Calwich Abbey, UK lake-silty clay loam sediment system accounted for up to 48.4 percent of the applied.  Therefore, the unidentified unextracted residues accounted for in aerobic aquatic metabolism studies for alkaline systems may comprise of additional levels of fenpyrazamine, S-2188-OH, and S-2188-DC degradates.  Likewise from soil, it is not expected that these residues will be bioavailable in the aquatic compartment of water bodies since residues remained incorporated in sediment after exhaustive extraction techniques in the study were employed.

Based upon the information described above from the environmental fate laboratory studies, the degradation pathway for aquatic environment is presented in Figure 2 below.

                             Incorporated Residues to Sediment Layer
.

Figure 2.  Proposed degradation and dissipation pathways in water.

   * Bioconcentration of Fenpyrazamine and Degradate Residues in Fish

Steady-state BCF values in fish between 7 -10 L/kg from edible tissues, non-edible tissues, and whole fish indicate that bioaccumulation potential of fenpyrazamine residues is low (MRID No. 48400005).  In addition, depuration of fenpyrazamine is negligible and fish tissue metabolism is high, since in the uptake phase, fenpyrazamine is transformed rapidly to S-2188-DC and S-2188-DC conjugate.  In the depuration phase, the major degradates that remained in edible fish tissue included S-2188-DC and the S-2188-DC conjugate which existed at maximum levels of 16.2 percent and 42 percent of total radioactive residues, respectively.  The depuration rates are rapid among the degradates.  The depuration half-life of the S-2188-DC degradate is 1.74 days and the S-2188-DC Conjugate is 10.1 days (MRID No. 48400005)[7].  Therefore, given the high metabolism of fenpyrazamine evident in fish and high depuration rates of the degradates, bioaccumulation in fish resulting from fenpyrazamine pesticide applications is not a concern.

   * Fate and Transport Characteristics of Transformation Products

The formation of all fenpyrazamine degradates in soil and water which form due to abiotic processes and biodegradation is shown in Appendix F.  The properties of the degradates of fenpyrazamine which form in soil and water are shown in Table 4 below.  Fenpyrazamine appears to be less mobile than its degradates as it is less soluble.  However, despite this difference, fenpyrazamine and its degradates all possess solubility values in the same range of pesticides which both dissolve in runoff water and partition to soils and sediments.  In addition, the log Koc values of degradates range between 2.20  -  3.67 indicating that they are slightly to moderately mobile based on the FAO classification scheme.  The Kd values of fenpyrazamine between 3.5 mL/g  -  8.7 mL/g (with one soil with a Kd value of 0.87 mL/g, see Table 3) further suggests that fenpyrazamine possesses mobility characteristics corresponding to the lower end of the range of that encompassing the degradates.  Fenpyrazamine's Koc values is not a valid model for comparison since its sorption is not highly correlated with organic carbon content.

Table 4.  Comparison of physical chemical properties of fenpyrazamine transformation products to parent fenpyrazamine.
                                   Property/
                          EPISuite Estimator Program
                         Value from Product Chemistry
                           EpiSuite Estimated Value

                                 Fenpyrazamine
                                   (S-2188)
                                   S-2188-OH
                                   S-2188-DC
                                  S-2188-DTC
                                     MCNI

                                     MPZZ
Molecular Weight
                                  331.4 g/mol
                                  247.3 g/mol
                                  231.3 g/mol
                                  271.4 g/mol
                                  216.3 g/mol
                                  189.2 g/mol
Solubility in Water
(25 °C)
(WSKOWWIN v. 1.42)
                                 20.4 mg/L[a]
                                  5,019 mg/L
                                  938.2 mg/L
                                  1,437 mg/L
                                  107.7 mg/L
                                 246,400 mg/L
Vapor Pressure
(25 °C)
(MPBPVP v. 1.43)
                            2.17 x 10[-10] torr[b]
                              2.66 x 10[-7] torr
                             2.87 x 10[-][7] torr
                              8.85 x 10[-8] torr
                              6.23 x 10[-7] torr
                              3.75 X 10[-6] torr
Henry's Law Constant (25 °C)
(HENRYWIN v. 3.20)
                        2.28 x 10[-10] atm·m[3]/mol[c]
                      7.30 x 10[-][13] atm·m[3]/mol[c]
                         9.31 x 10-11 atm·m[3]/mol[c]
                        2.20 x 10[-11] atm·m[3]/mol[c]
                        1.65 x 10[-9] atm·m[3]/mol[c]
                        4.23x 10[-10] atm·m[3]/mol[c]
Octanol-Water Partition Coefficient
(Log Kow)
(WSKOWWIN v. 1.42)
                                    3.52[d]
                                     0.81
                                     0.23
                                     1.28
                                     2.65
                                     0.38
Soil-Water Partition Coefficient (Koc)
(KOCWIN v. 2.00)
                                    N/A[e]
                                  158.6 mL/g
                                  1,302 mL/g
                                  4,633 mL/g
                                  428.1 mL/g
                                  1,704 mL/g
*Only degradates found in environmental fate laboratory and field studies in soil and water are shown in table.
[a]  Value at 20°C from MRID No. 4839915.
[b]  From MRID No. 48399916.
[c]  From EpiSuite HENRYWIN v. 3.20.
[d]  From MRID No. 48399914.
e  N/A means not available since Koc is not a good measure or sorption to soil or sediment..

The degradation half-lives of the transformation products for fenpyrazamine cannot be determined at this time based on the existing data from laboratory studies (see Table 3 for further information).  The durations of environmental fate studies were insufficient to determine the complete formation and decline rates of the degradates which are needed to complete this analysis.  This information has not been found upon inspection of open literature nor have data been identified among common degradates from existing active ingredients.  However, the maximum formations of degradates detected in environmental fate laboratory and field studies can be found in Appendix F..

   * Uncertainties and Limitations

There are several significant uncertainties with the environmental fate profile of fenpyrazamine.
The first major uncertainty concerns fenpyrazamine's rate of hydrolysis in the environment.  The existing hydrolysis study suggests that fenpyrazamine degrades over all environments, especially in alkaline environments, with metabolites S-2188-OH and S-2188-DC detected (MRID No. 48399923).  This is also evident from the aerobic aquatic metabolism study (MRID No. 48399929), which also shows a trend of decreased half-lives at higher pHs, suggesting that hydrolysis mediates degradation in alkaline environments.  However, environmentally relevant hydrolysis data at 25°C were not provided to the Agency for neutral environments (pH7),  including the rate of degradation as well as the levels of the transformation products for fenpyrazamine.  Additional hydrolysis information would confirm the rate of degradation, as well as the levels of the transformation products of fenpyrazamine at pH7 and 25°C at environmentally relevant conditions.

A second significant uncertainty relates to the limited sediment - water systems evaluated in the anaerobic aquatic study (MRID No. 48399930).  Only one system was evaluated in each study.  Additional water  -  sediment systems would provide a sufficiently robust dataset showing the distribution of microbial degradation.

 A third uncertainty regards unextracted residues incorporated in soil or sediment layers.  In soil, unextracted residues accounted for approximately up to 70 percent of applied in two alkaline soils in aerobic soil metabolism studies (MRID No. 48399920).  In water, unextracted residues in sediment from the Calwich Abbey, UK study sample accounted for up to 48.4 percent of applied.  It should be noted that unextracted residues are likely bonded chemically to the humin matrices within the soil and sediment layers.  Soil-water partition coefficients of fenpyrazamine and degradates as well as inconsistencies in the amount of unextracted residues between the aerobic and anaerobic aquatic metabolism studies suggest that unextracted residues are not forming due to sorbtion of  fenpyrazamine.

 A fourth uncertainty which exists is that water-sediment systems with variable pHs were evaluated in the aerobic aquatic metabolism study.  Since degradation is much different between acidic and alkaline conditions, it appears that degradation is mediated pH.

The fifth uncertainty concerns the little availability of batch equilibrium studies conducted on domestically representative soils. The organic-carbon normalized partition coefficient (Koc) were only examined for a loamy sand soil from California and a silt loam soil from New Jersey (MRID No. 48399922).  The remaining soils were evaluated from the UK and Japan (MRID No. 48399919).  The UK soils are traditionally similar to the physical and chemical composition of soils in the United States.  However, soils in Japan traditionally possess volcanic elements which are found over very limited areas in the United States.  However, data that are available for five other foreign soils in the UK appear to confirm the moderate mobility of fenpyrazamine observed in the domestic soils.  Additional information on the taxonomic properties of the foreign soils would confirm their representativeness to US soils.

         2. ECOLOGICAL TOXICITY CHARACTERIZATION

         4.1 Receptors

 Ecological measures of effect for this screening level risk assessment are based on a suite of registrant-submitted toxicity studies performed on a limited number of organisms in broad groupings.  Table 5 gives examples of taxonomic groups and test species evaluated for ecological effects in this screening level risk assessment.  Within each of these very broad taxonomic groups, an acute and/or chronic endpoint is selected from the available test data (see Table 6).

Table 5.  Taxonomic groups and test species evaluated for ecological effects in this screening-level risk assessment
 Taxonomic group
 Representative species
 Birds [a]
 Mallard duck (Anas platyrhynchos)
 Bobwhite quail (Colinus virginianus)
 Canary (Serenris canaria)
 Mammals
 Laboratory rat (Rattus norvegicus)
 Terrestrial Invertebrates
Honey bee (Apis mellifera)
Earthworm (Eisenia fetida)
 Freshwater fish [b]
Bluegill sunfish (Lepomis macrochirus)
Rainbow trout (Oncorhynchus mykiss)
Freshwater Invertebrates
Water flea (Daphnia magna)
Estuarine/marine Fish
Sheepshead minnow (Cyprinodon variegatus)
Estuarine/marine Invertebrates
Mysid shrimp (Americamysis bahia), Eastern oyster (Crassostrea virginica)
Benthic Freshwater Invertebrates
Amphipod (Hyalella azteca)
Freshwater midge (Chironomus riparius)
Benthic Estuarine/Marine Invertebrates
Amphipod (Leptocheirus plumulosus)
Aquatic Plants and Algae
Duckweed (Lemna gibba)
Green algae (Pseudokirchneriella subcapitata)
Marine diatom (Skeletonema costatum)
Freshwater diatom (Navicula pelliculosa)
Cyanobacteria (Anabaena flos-aquae)
Terrestrial Plants
Multiple species
[a] Birds may be surrogates for amphibians (terrestrial phase) and reptiles.
[b] Freshwater fish may be surrogates for aquatic phase amphibians.

For screening risk assessments, the following toxicity endpoints presented in Table 6 are used as inputs to the risk quotient (RQ) method for expressing risk (US EPA, 2004).  Details of the risk quotient method and its associated LOCs are found in Appendix A.  The designation of "listed species" refers to either federally threatened or endangered species.

Table 6.  Toxicity endpoints used in risk quotient calculations.
 Taxonomic group
 Representative species
Aquatic Animals
Acute assessment

Chronic assessment

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

Lowest no-observed-adverse-effects- concentration (NOAEC) for freshwater fish and invertebrates and estuarine/marine fish and invertebrates early life-stage tests.
Terrestrial Animals
Acute avian assessment

Chronic avian assessment

Acute mammalian assessment

Chronic mammalian assessment

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

Lowest NOAEC for 21-week avian reproduction test.

Lowest LD50 from single oral dose test.

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

Aquatic vascular and algae

Terrestrial listed species

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

Lowest EC50 for both aquatic vascular plants and algae.

Lowest EC05 or NOAEC for both seedling emergence and vegetative vigor for both monocots and dicots.
 [a] Freshwater fish may be surrogates for amphibians (aquatic phase).
 [b] Birds may be surrogates for amphibians (terrestrial phase) and reptiles.

 Acute and chronic laboratory and field tests on fenpyrazamine on aquatic organisms provide information regarding lethality, as well as sublethal measures of effect.  Data are available on the technical grade active ingredient (TGAI) and the effects on freshwater and estuarine/marine fish and invertebrates, aquatic vascular and nonvascular plants (algae), and freshwater and estuarine/marine sediment dwelling organisms.  Additionally acute toxicity data were available for certain degradation/transformation products of fenpyrazamine on rainbow trout, daphnia magna, and freshwater green algae.  These studies will be discussed with the other toxicity data in Section 4.4 of this assessment.

 For terrestrial effects, registrant-submitted studies on fenpyrazamine technical are available for acute, subacute dietary, and chronic exposure to birds, and acute and chronic exposure to mammals.  Additional ecological effects data for fenpyrazamine are available for honey bees and earthworms.  Finally, data on the effects of seedling emergence and vegetative vigor for ten species were submitted in support of fenpyrazamine.

         4.1 Ecosystems at Risk

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

 Aquatic ecosystems potentially at risk include water bodies adjacent to (or downstream from) the treatment area and might include impounded bodies such as ponds, lakes, reservoirs and wetland areas, or flowing waterways such as streams and rivers. For uses in coastal areas, aquatic habitat also includes marine ecosystems, including estuaries and salt marshes.  Additionally freshwater and estuarine/marine benthic zones are at potential risk due to fenpyrazamine's moderate persistence and mobility suggesting its potential to translocate and reside in water bodies.

         4.1 Assessment Endpoints

 Assessment endpoints represent the actual environmental value that is to be protected, defined by an ecological entity (species, community, or other entity) and its attribute or characteristics (US EPA, 1998).    For the proposed fenpyrazamine uses, the ecological entities may include the following:  birds, mammals, freshwater fish and invertebrates, estuarine/marine fish and invertebrates (pelagic and benthic dwelling), insects, and aquatic and terrestrial plants. The attributes for each of these entities may include growth, reproduction, survival, biomass (standing crop for plants). For both aquatic and terrestrial animal species, direct acute and direct chronic effects are considered.  Although these endpoints are measured at the individual level, they provide insight about risks at higher levels of biological organization (such as populations and communities).

         4.1 Ecological Effects Characterization

 The effects of fenpyrazamine on aquatic and terrestrial organisms as derived from laboratory studies are summarized in this section.  It is important to recognize that the toxicity test results reported herein represent a small fraction of avian, mammalian, aquatic organisms and plant species resident to North America. Specifically, only a few surrogate species for both freshwater fish and birds are used to represent all freshwater fish (2000+) and bird (680+) species in the United States.  For mammals, acute studies are usually limited to Norway rat or the house mouse.  Estuarine/marine testing is usually limited to a crustacean, a mollusk, and a fish.  Also, neither reptiles nor amphibians are commonly tested.  In the absence of toxicity data for reptiles and terrestrial phase amphibians, this risk assessment uses the sensitivity of birds as a surrogate for terrestrial-phase amphibians and reptiles.  Similarly, freshwater fish are used as a surrogate for aquatic-phase amphibians.

 In general, categories of acute toxicity ranging from "practically nontoxic" to "very highly toxic" have been established for aquatic organisms (based on LC50 and EC50 values or limit of solubility), mammals (based on LD50 values), avian species (based on  LD50 and  LC50 values), and non-target insects (based on LD50 values for honey bees) (U.S. EPA 2001).

                     4.4.1 Aquatic Effects

The acute and chronic toxicity values associated with freshwater and estuarine/marine species exposure to fenpyrazamine are summarized in Table 7.  Toxicity endpoints shown in bold represent the most sensitive endpoints within a taxonomic grouping (e.g., freshwater fish, freshwater invertebrates, aquatic plants, etc.).  These endpoints are termed the "toxicity reference values" which are used for this quantitative risk assessment.  All acute, chronic, and subchronic exposures to animals as well as exposures to plants are expected given fenpyrazamine's moderate persistence and mobility suggesting its potential to translocate and reside in water bodies.  Studies that were submitted with various degradation products of parent fenpyrazamine are summarized in Table 8.

Table 7.  Toxicity reference values for aquatic organisms exposed to fenpyrazamine.
                               Exposure Scenario
                                     % A.I.
                                    Species
                                      Dur.
                           Toxicity Reference Value
                                    (95% CL)
                                  Effect Notes
                                     MRID;
                             Classifi-cation (Year)
 Freshwater Fish
                                     Acute
                                      TGAI
                                     94.7%
 Rainbow Trout
 Oncorhynchus mykiss
 96 h
 LC50  = 5.2 mg a.i./L (3.8  -  7.8)
 Probit Slope = N/A

   * 100% mortality was observed in the highest treatment concentration (7.8 mg a.i/L, mean measured).
   * 5% or less mortality was observed in the controls and remaining treatment concentrations
   * Varying number of fish in the three highest treatment concentrations (2.1, 3.8, and 7.8 mg a.i/L, mean measured) were lethargic

                                    48399945
                                   Acceptable
                                     (2006)
                                     Acute
                                      TGAI
                                     94.7%
 Bluegill sunfish (Lepomis macrochirus)
                                      96 h
 LC50  =  5.4 mg ai/L (3.4  -  6.9)
 Probit Slope = N/A

   * There was 85 and 100% mortality in the two highest treatment concentrations (6.9 and 12 mg a.i/L mean measured, respectively)
   * 0% mortality occurred in the controls and all other treatment concentrations (0.88, 1.8, and 3.4 mg a.i/L)
   * All fish in highest treatment group exhibited a complete loss of equilibrium after three hours of exposure and were dead by six hours
                              48399944 Acceptable
                                     (2006)
                                    Chronic
                                      TGAI
                                     94.7%
 Rainbow Trout
 (Oncorhynchus mykiss)
                                      90 d
 NOAEC (survival at hatch, survival at test termination) = 370 ug a.i./L
 LOAEC = 750 ug a.i./L
   * Embryo viability averaged 62  -  70% across the controls and all treatment concentrations
   * Day-0 post hatch survival of larvae ranged from 96  -  100% across the controls and all treatment concentrations
   * Day-60 post hatch survival was significantly reduced at the highest treatment concentration
   * Total length, wet weight, and dry weight were not significantly reduced at any treatment level (highest treatment level excluded from analysis due to effects on survival)
   *
   *

                                    48400003
                                   Acceptable
                                     (2006)

 Freshwater Invertebrates
                                     Acute
                                      TGAI
                                     94.7%
 Water flea
 Daphnia magna
                                      48 h
 EC50  = 5.5 mg a.i/L (4.6  -  6.5)
 Probit Slope: 10.2 (6.1  -  14.2)

   * 0% mortality in negative and solvent control as well as three lowest treatment groups
   *  95% mortality at highest treatment group (8.0 mg a.i/L)
   * Lethargy among surviving daphnids observed in all treatment groups
                              48399939 Acceptable
                                     (2006)
                                    Chronic
                                      TGAI
                                     94.7%
 Water flea
 Daphnia magna
                                      21 d
 NOAEC: 0.34 mg a.i/L
 LOAEC: 0.76 mg a.i/L
   * There were no treatment related effects on survival
   * Number of offspring released by females was significantly reduced (p<0.05) at the two highest treatment concentrations (0.76 and 1.4 mg a.i/L, mean measured)
   * Body lengths of surviving daphnid were significantly reduced (p<0.05) at the two highest treatment concentrations
   * Dry weights of surviving daphnids were statistically reduced (p<0.05) at the highest treatment concentration only
   * There was a delayed time to first brood compared to the controls at the two highest treatment concentrations (Day 9 at 0.76 mg a.i/L, Day 10 at 1.4 mg a.i/L, compared to Day 7 for controls and all other treatment concentrations
   * Immobilized offspring, if any, were not reported
                              48400001 Acceptable
                                     (2006)
 Estuarine/Marine Fish

                                     Acute
                                      TGAI
                                     98.8%
 Sheepshead minnow
 (Cyprinodon variegatus)
                                      96 h
 LC50: >3.9 mg ai/L (95% CI N/A)
 Probit Slope: N/A

   * 20% mortality occurred in the 3.9 mg a.i/L treatment concentration (mean measured), the highest treatment concentration
   * There was no mortality in the negative control or any other treatment concentration
   * There were no clinical signs of toxicity or sublethal effects observed in the negative control or any treatment concentrations except the highest in which several surviving fish were lethargic, and two surviving fish exhibited a partial loss of equilibrium.
                                    48399946
                                   Acceptable
                                     (2010)
                                    Chronic
 TGAI 98.8%
 Sheepshead minnow
 (Cyprinodon variegatus)
 33 d
 NOAEC (length) = <0.039 mg a.i/L
 LOAEC (length) = 0.039 mg a.i/L
   * No treatment-related effects on hatching success or post hatch larval survival were observed
   * Statistically significant (p<0.05) effects on length observed at all treatment concentrations
   * Dry weight effects were statistically significant (P,0.05) at the two highest treatment concentrations (0.58 and 1.2 mg a.i/L)
   * Time to hatch and clinical signs of toxicity (if any) were not reported

                                    48400004
                                  Supplemental
                                     (2010)
 Estuarine/Marine Invertebrates

                                     Acute
                                      TGAI
                                     98.8%
 Saltwater mysid (Americamysis bahia)
                                      96 h
 LC50 = 0.83 mg ai/L (0.62  -  1.2)
 Probit Slope: N/A

   * 100% mortality occurred at three highest treatment concentrations (1.2, 2.3, and 4.6 mg a.i/L, mean measured)
   *  All mysids in the control and lowest treatment concentration (0.29 mg a.i/L, mean measured) appeared normal and healthy throughout the study

                                    48399941
                                   Acceptable
                                     (2010)

                                      TGAI
                                     98.8%
 Eastern Oyster (Crassostrea virginica)
                                      96 h
 EC50 = 0.78 mg ai/L (0.58  -  1.1 mg ai/L)
 NOAEC= 0.49 mg ai/L
   * Shell growth was reduced by 30.4, 21.7, 21.7, 30.4, and 73.9 relative to controls at 0.066, 0.12, 0.24, 0.49, and 1.0 mg ai/L, respectively (mean measured).
                                    48399940
                                   Acceptable
                                     (2010)

                                    Chronic
                                      TGAI
                                     98.8%
 Saltwater mysid (Americamysis bahia)
                                      38 d
 NOAEC = 98 ug a.i./L
 LOAEC50 = > 98 ug a.i./L

   * Mysids exposed to control, 3.2, 6.8, 13, 24, 47, and 98 ug a.i/L mean measured treatment concentrations
   * There were no significant reductions (p<0.05) for time to first brood release, F0 survival, F1 survival, male and female dry weight, and male total body length
   * While there was a significant reduction at the lowest treatment concentration for number of offspring per female, this was the only treatment concentration affected
   * Female total body length was significantly (p<0.05) reduced at the lowest and two highest treatment concentration yet their percent effect as compared to the negative control were between 2.5  - 5.3%.  As the effect did not follow a dose response pattern and was not considered to be biologically significant, the NOAEC was determined as the highest treatment concentration
                                    48400002
                                   Acceptable
                                     (2010)
 Freshwater Benthic Invertebrates
                                    Chronic
                                      TGAI
                                     98.8%
 Freshwater amphipod, (Hyalella azteca)
                                      42 d
 Sediment value: NOAEC (35-d survival and reproduction, 42-d survival) =5.7 mg a.i./kg dw

  Porewater value: NOAEC (35-d survival and reproduction, 42-d survival)  = 0.5 mg a.i/L
   * Mean percent survival after 42 days was 95, 93, 93, 77, 61, 71, and 24 mg a.i/kg sediment for the negative control, solvent control, and time weighted average sediment concentrations of 5.7, 10, 24, 38, and 97 mg a.i/kg sediment levels, respectively
   *  Growth and reproduction data were dropped from analysis for 28-d dry weight, 35-d number of offspring, and 42-d  dry weight, number of offspring, and male to female ratio because of significant effects on survival at these intervals for varying concentrations
                                   48400006
                                   Acceptable
                                     (2010)

 TGAI 94.7
 Freshwater midge
 (Chironomus riparius)
 28 d
 Sediment value: NOAEC (development rate) = < 0.101 ug a.i/kg dw

 Pore water value:
 NOAEC (development rate) = <0.20 ug a.i/L
   * Test vessels were spiked once via overlying water
   * Overlying water concentrations decline over time, while pore water and sediment concentrations increased
   * Percent emergence was 75% or greater at all concentrations
   * Definitive NOAEC was not reached for development rate due to effects at lowest treatment level
                                    48400007
                                  Supplemental
                                     (2009)
 Estuarine/Marine Benthic Invertebrates
                                    Chronic

                                     Acute

                                      TGAI
                                     98.8%
 Saltwater amphipod
 (Leptocheirus plumulosus)
                                      28 d
 Sediment value:
 NOAEC/LOAEC = <3.0/6.3 mg a.i/kg dw (dry weight)

 Pore water value:
 NOAEC/LOAEC = <0.25/0.5 mg a.i/L  (dry weight)

   * Total mortality observed at highest two concentrations (25 and 50 mg a.i/kg sediment
   * Dry weight and number of offspring per female not significantly affected at two lowest treatment levels (3.0 and 6.3 mg a.i/kg sediment).
                                   48400008
                                  Supplemental
                                     (2010)
 Aquatic Plants
                                Vascular plants

                                      TGAI
                                     98.8%
 Duckweed (Lemna gibba)
                                      7 d
 EC50 (frond weight):  1.1 mg a.i./L (1.2  -  1.8)
 NOAEC (frond weight):  0.60 mg a.i./L
   * The percent growth inhibition for treatment concentrations compared to the negative control ranged from -11  -  79% based on frond density, 1  -  9% based on frond weight, and 5  -  55% based on day 0  -  7 growth rate
   * Fronds in the two highest treatment concentrations (2.3 and 5.9 mg a.i/L, mean measured) had reduced root development relative to control fronds.
                              48400018 Acceptable
                                     (2010)
                                 Algal toxicity
                                      TGAI
                                     98.8%
Cyanobacteria
(Anabaena flos-aquae)
                                      96 h
 EC50  (cell density): 1.2 mg a.i/L (0.21  -  2.5)

 NOAEC (cell density, growth rate, biomass): 0.74 mg a.i/L

   * The percent growth inhibition in treatment concentrations compared to the negative control ranged from 12  -  87% based on cell density.

                                    48400024
                                   Acceptable
                                     (2010)

                                      TGAI
                                     94.7%
Freshwater Green algae
(Pseudokirchneriella subcaipta)
                                      96 h
 EC50 (cell density): 0.16 mg a.i/L (0.12  -  0.22)

 NOAEC (cell density): <0.053 mg a.i/L

 EC05 (cell density): 0.029 mg a.i/L (0.015  -  0.055)*

   * The percent growth inhibition in the treatment concentrations compared to the negative control ranged from 26  -  95% based on cell density, 5  -  48% based on growth rate, and 15  -  92% based on biomass.
   * At test termination, cells in the highest treatment concentration (0.9 mg a.i/L, mean measured) were observed to be bloated.
                                    48400021
                                   Acceptable
                                     (2008)
                                 Algal toxicity
                                      TGAI
                                     98.8%
Marine diatom
(Skeletonema costatum)
                                      96 h
 EC50 (cell density): 0.027 mg a.i/L (0.024  -  0.035)

 NOAEC (cell density): <0.0045 mg a.i/L
 EC05: 0.002 (95% CI  N/A)*
   * The percent growth inhibition in the treatment concentrations compared to the negative control ranged from 3  -  97% based on cell density, the most sensitive endpoint.
                                   48400022
                                   Acceptable
                                     (2010)

                                   TGAI 98.8%
Freshwater diatom
(Navicula pelliculosa)
                                      96 h
 EC50: (cell density): 0.011 mg a.i/L (0.10  -  0.012)
 NOAEC (cell density): 0.0049 mg a.i/L
   * The percent growth inhibition in the treatment concentrations compared to the negative control ranged from -11  -  99% on cell density.
                                   48400023
                                   Acceptable
                                     (2010)
*EFED policy is to use the EC05 for estimation of risk to endangered aquatic plant in the event the NOAEC is non-definitive.
Bolded values refer to the most sensitive endpoint for a given taxa to be used in quantitative risk assessment.

Table 8.  Toxicity Reference Values For Aquatic Organisms Exposed to Degradation Products of Fenpyrazamine.
                              Degradation product
                                     % A.I.
                                    Species
                                      Dur.
                           Toxicity Reference Value
                                    (95% CL)
                                  Effect Notes
                                     MRID;
                             Classifi-cation (Year)
 Freshwater invertebrates
 MCNI

 TGAI
 100%
 Water flea
 (Daphnia magna)
 48 h
 EC50: >50 mg a.i/L (95% CI N/A)
 Probit Slope: N/A

   * Daphnids exposed to negative control, solvent control and limit concentration of 50 mg a.i/L which represents the degradation product's limit of solubility.
   *  There were no mortality or sublethal effects observed in the controls or the single treatment concentration
                                   48399936
                                   Acceptable
                                     (2008)
 S-2188-OH
 TGAI
 98.4%
 Water flea
 (Daphnia magna)
 48 h
 EC50 : >98 mg a.i/L (95% CI N/A)
 Probit slope: N/A
   * Daphnids were exposed to negative control and limit concentration of 98 mg a.i/L, mean measured
   *  There were no mortality or sublethal effects observed in the control or the single treatment concentration
                                   48399937
                                  Acceptable
                                    (2008)
 S-2188-DC
 TGAI 100%
 Water flea
 (Daphnia magna)
 48 h
 EC50 : >94 mg a.i/L (95% CI N/A)
 Probit slope : N/A
   * Daphnids were exposed to negative control and limit concentration of 94 mg a.i/L, mean measured
   *  There was no mortality and surviving daphnids in the sole treatment concentration were observed to have abnormal swimming
                                   48399938
                                  Acceptable
                                    (2008)
 Freshwater Fish
 S-2188-DC
                                      TGAI
                                      100%
 Rainbow trout
 (Oncorhynchos mykiss)
                                      96 h
 LC50: > 89 mg a.i/L (95% CI N/A)
 Probit slope: N/A
   * Fish were exposed to negative control and limit concentration of 89 mg a.i/L, mean measured
   *  There was no mortality or sublethal effects observed in the control or the single treatment concentration
                              48399942 Acceptable
                                     (2008)
 S-2188-OH
                                      TGAI
                                     98.4%
 Rainbow trout
(Oncorhynchos mykiss)
                                      96 h
 LC50: > 97 mg a.i/L (95% CI N/A)
 Probit slope: N/A
   *  Fish were exposed to negative control and limit concentration of 97 mg a.i/L, mean measured
   * There was no mortality or sublethal effects observed in the control or the single treatment concentration

                                    48400043
                                   Acceptable
                                     (2008)
 Algal Toxicity
 S-2188-DC
 TGAI
100%
Freshwater Green algae
 (Pseudokirchneriella subcapita)
                                      96 h
 EC50 (cell density): 32 mg a.i/L (30-35)

 NOAEC (cell density): 1.6 mg a.i/L
   * The percent growth inhibition I the treatment concentrations as compared to the negative control ranged from 1.1 to 89.3% based on cell density, 0.3 to 22.6% based on growth rate, and 1.1 to 57.6% based on biomass.

                                    48400019
                                   Acceptable
                                     (2008)
 S-2188-OH
 98.4
Freshwater Green algae
 (Pseudokirchneriella subcapita)
                                      96 h
 EC50 (cell density): 55 mg a.i/L) (46-65)

 NOAEC (cell density): 3.1 mg a.i/L
   * The percent growth inhibition in the treatment concentrations as compared to the negative control ranged from -2.3 to 72% based on cell density, -0.37 to 20% based on growth rate, and -1.2 to 66% based on biomass.
                                    48400020
                                   Acceptable
                                     (2008)

   *                         Freshwater Fish

Acute toxicity studies with technical-grade fenpyrazamine were available for 2 species of freshwater fish: rainbow trout and bluegill sunfish.  All studies were conducted on TGAI with 94.7% purity.  In the rainbow trout study (MRID 48399945), fenpyrazamine was administered in a flow-through exposure system and caused 100% mortality at the highest treatment concentration (7.8 mg a.i/L, mean measured).  All other treatment concentrations and control had mortality at or below 5%.  There were no sublethal effects noted in the lowest two treatment concentrations.  At the two higher treatment concentrations (2.1 and 3.8 mg a.i/L, mean measured), 7 and 20 fish exhibited lethargy in those treatment concentrations, respectively.  In the bluegill sunfish study (MRID 48399944), TGAI fenpyrazamine was administered in a flow through system.  The two highest treatment concentrations (6.9 and 12 mg a.i/L, mean measured) had 85 and 100 % mortality, respectively while the controls and other treatment concentrations had 0% morality during the study.  All fish in the highest treatment concentration exhibited a complete loss of equilibrium after three hours of exposure and were dead by six hours.  This study has an LC50 of 5.4 mg a.i/L and is classified as acceptable.  For risk assessment purposes, an acute toxicity value of 5.2 mg a.i/L (MRID 48399945) will be used for estimating acute risk quotients for freshwater fish.

There were two additional acute freshwater fish toxicity studies submitted with degradation products of fenpyrazamine.  Both studies were conducted with the rainbow trout.  In one study conducted with 98.4% purity of degradation product S-2188-OH (MRID 48400043 ) at a single treatment concentration (97 mg a.i/L, mean measured), there were no mortalities or sublethal effects observed.  This study has an LC50 of 5.2 mg a.i/L and is classified as acceptable.  In another acute study conducted with 100% purity S-2188-DC (MRID 48399942), there were no mortalities or sublethal effects noted at the sole treatment concentration in the study, 89 mg a.i/L, mean measured.  This study has an L50 of >89 mg a.i/L and is classified as acceptable.

An acceptable chronic early life stage test with a freshwater fish (rainbow trout, MRID 48400003) was conducted with TGAI fenpyrazamine (94.7% purity).  Fertilized egg/embryos were exposed at mean measured concentrations of 50, 100, 190, 370, and 750 ug a.i/L.  Embryo viability was determined on Day 19 and averaged 62 and 67% for the negative and solvent controls, respectively, and 70, 69, 70, 61, and 68% for the increasing treatment concentrations, respectively.  On day 30 of the study (Day 0, post-hatch) larval survival was significantly reduced (p<0.05) at the highest treatment concentration.  On day 90 of the study (Day 60, post-hatch) larval survival was also significantly reduced (p<0.05) only at the highest treatment concentration as compared to the negative control.  Mean total length, wet weight, and dry weight data were excluded for the highest treatment concentration due to effects on larval survival at that treatment concentration.  For those three endpoints, there were no significant reductions (p<0.05) as compared to the negative control.  The NOAEC and LOAEC for this study was determined to be 370 and 750 ug a.i/L, respectively based on effects to Day-0 post hatch larval survival and Day-60 post hatch larval survival.  For risk assessment purposes, a chronic toxicity of 370 ug a.i/L will be used for estimating chronic risk quotients for freshwater fish.

   *                         Freshwater Invertebrates

An acute toxicity study conducted with TGAI fenpyrazamine (94.7%) on freshwater invertebrates was available for Daphnia magna.  A 48-h EC50 of 5.5 mg a.i/L was determined on the basis of immobilization.  Mortality/immobilization was 95% at the highest treatment concentration (8.0 mg a.i/L, mean measured), 5% at the second highest treatment concentration (3.8 mg a.i/L, mean measured) and 0% at the remaining treatment concentrations and controls.  There was a 55% portion of daphnids observed to be lethargic at test termination in the lowest treatment concentration (0.61 mg a.i/L, mean measured) while 100% of the surviving daphnids in the remaining treatment concentrations were observed to be lethargic.  This study is classified as acceptable.  For risk assessment purposes, an acute toxicity of 5.5 mg a.i/L will be used for estimating acute risk quotients for freshwater invertebrates.

There were three additional acute freshwater invertebrate toxicity studies submitted with degradation products of fenpyrazamine.  All studies were conducted with the Daphnia magna.  In one study conducted with 98.4% purity of degradation product S-2188-OH (MRID 48399937) at a single treatment concentration (98 mg a.i/L, mean measured), there were no mortalities or sublethal effects observed and therefore this study had an EC50 value determined to be >98 mg a.i/L.  In another acute study conducted with 100% purity S-2188-DC (MRID 48399938), there were no mortalities or sublethal effects noted observed in the study and therefore the study had an EC50 determined to be >94 mg a.i/L.  Finally, a study with the degradation product MCNI (100% purity) (MRID 48399936) was submitted and conducted with a sole treatment concentration of 50 mg a.i/L which represents the limit of solubility for this degradate.  There were no mortalities or sublethal effects observed during the study and therefore the EC50 was determined to be >50 mg a.i/L.  All studies were classified as acceptable.

A freshwater invertebrate (Daphnia magna) lifecycle test with fenpyrazamine TGAI (94.7%) was submitted and found to be acceptable (MRID 48400001).  Daphnids were exposed throughout their life cycle to mean measured concentrations of fenpyrazamine ranging from 0.085 to 1.4 mg a.i/L for 21 days. Survival ranged from 90 to 100% for all levels, with no statistically-significant differences indicated at any treatment level compared to the negative control.  The cumulative number of offspring released per female after 21 days was significantly reduced (p<0.05) at the two highest treatment concentrations (0.76 and 1.4 mg a.i/L, mean measured) as compared to the negative control.  The number of immobilized offspring, if any, was not reported.  At study termination, mean total body lengths of surviving daphnia were significantly reduced (p<0.05) compared to the negative control at the two highest treatment concentrations.  Mean dry weights of surviving daphnia were only significantly reduced (p<0.05) at the highest treatment concentration.  It was reported that the first brood released occurred on Day 7 at the negative control, solvent control, and the three lowest treatment concentrations (0.085, 0.18, and 0.34 mg a.i/L, mean measured).  At the second highest treatment concentration, this time was Day 9 and at the highest treatment concentration this time was Day 10.  There were no conclusions drawn by the study author, but the data support a treatment-related delay at the two highest treatment concentrations for time to first brood. The most sensitive endpoints of the study were time to first brood release and total length of surviving daphnids with NOAEC and LOAEC values of 0.34 and 0.76, respectively.  For risk assessment purposes, a chronic toxicity value of 0.34 mg a.i/L will be used for estimating chronic risk quotients for freshwater invertebrates.
   *                         Estuarine/Marine Fish

 One acute toxicity study was submitted conducted with TGAI fenpyrazamine (98.8% purity) to the sheepshead minnow (MRID 48399946).  Mortality was observed at 20% in the highest test concentration (3.9 mg a.i/L, mean measured) but was 0% in all other treatment concentrations.  There were no sublethal effects observed in the negative control and all treatment concentrations except the highest.  At the 3.9 mg a.i/L level, there were several (number not defined in the study report) fish that were reported as being lethargic and two surviving fish that exhibited a partial loss of equilibrium.  The LC50 for this study was determined to be >3.9 mg a.i/L and this study is classified as acceptable.  For risk assessment purposes, an acute toxicity value of 3.9 mg a.i/L will be used for estimating acute risk quotients for estuarine/marine fish (i.e., a lower bound of 3.9 mg a.i/L will be assumed as a screen for acute effects).

An estuarine/marine chronic fish early life stage test conducted with fenpyrazamine TGAI (98.8%) on the sheepshead minnow was submitted and found to be supplemental (non-definitive NOAEC for most sensitive endpoint and clinical signs of toxicity not noted, MRID 48400004).  Embryos to their larval stage were exposed to fenpyrazamine levels ranging from 0.039 to 1.2 mg a.i/L for 33 days.  There were no treatment-related effects on hatching success (assessed on Day 5) or post-hatch survival) assessed on Day 33) observed with no significantly different (p<0.05) effects when compared to the negative control.  Mean percent hatching success ranged from 92 to 98% across all treatment concentrations (including the negative control) and mea larval survival ranged from 95 to 100%.  Total length measurements were significantly reduced from the negative control (p<0.05) at all treatment levels.  Dry weights were significantly reduced (p<0.05) at the two highest treatment concentrations (0.58 and 1.2 mg a.i/L, mean measured).  The most sensitive endpoint of the study was total length of surviving larval fish with NOAEC and LOAEC values of <0.039 and 0.039 mg a.i/L, respectively.  For risk assessment purposes, a chronic toxicity value of 0.039 mg a.i/L will be used for estimating chronic risk quotients for freshwater fish (i.e., an upper bound of 0.039 mg a.i/L will be assumed as a screen for chronic effects).
   *                         Estuarine/Marine Invertebrates

 Acceptable acute toxicity studies were available for two species of estuarine/marine invertebrates: the mysid shrimp (Americamysis bahia; MRID 48399941) and eastern oyster (Crassotrea virginica; MRID 48399940, both conducted with TGAI fenpyrazamine (98.8% purity). With mysids, a 96-h LC50 value of 0.83 mg a.i/L was determined from the study.  Total mortality occurred in the three highest treatment concentrations (1.2, 2.3, and 4.6 mg a.i/L, mean measured).

 With the eastern oyster, a 96-h EC50 for shell deposition was determined to be 0.78 mg a.i/L.  Shell growth was reduced by 30.4, 21.7, 21.7, 30.4, and 73.9 % relative to the negative control at the 0.066, 0.12, 0.24, 0.49, and 1.0 mg a.i/L treatment concentrations, respectively (mean measured concentrations).  There was no mortality observed in the study.   For risk assessment purposes, an acute toxicity value of 0.78 mg a.i/L will be used to assess acute risks to estuarine/marine invertebrates.

An estuarine/marine invertebrate (Americamysis bahia) lifecycle test with fenpyrazamine TGAI (98.8 %) was submitted and found to be acceptable (MRID 48400002).  Mysids were exposed throughout their life cycle to mean measured concentrations of fenpyrazamine ranging from 3.2  -  98 ug a.i/L for 28 days.  Parental survival ranged from 83 - 100% for all levels, with no statistically-significant differences indicated at any treatment level compared to the negative control.  The cumulative number of offspring released per female after 28 days was also not significantly reduced (p<0.05) at any of the treatment concentrations.  Male and female mean dry weight, time to first brood release and male mean total length were also not significantly reduced from the negative control.  For female total body length, statistical hypothesis testing determined a significant effect (p<0.05) at the 3.2, 47, and 98 ug a.i/L treatment concentrations.  However these effects were 3.5, 5.3 and 2.5 % reductions from the negative control and because they did not follow a dose responsive pattern, it was determined that the NOAEC for this endpoint was the highest treatment concentration (98 ug a.i/L) for which there was a 2.5 % reduction from control.  Therefore the NOAEC and LOAEC for this study were 98 and >98 ug a.i/L, respectively.  For risk assessment purposes, a chronic toxicity value of 98 ug a.i/L will be used for estimating chronic risk quotients for estuarine/marine invertebrates (i.e., a lower bound of 98 ug a.i/L will be assumed as a screen for chronic effects).
   *                         Benthic (Sediment Dwelling) Invertebrates

 Effects of fenpyrazamine on freshwater benthic invertebrates are available from two studies: a 42d exposure via spiked sediment to the amphipod Hyalella azteca (MRID 48400006) and a 28d exposure via spiked overlying water to the midge Chironomus riparius (MRID 48400007).  In the Hyalella study, 8 day old amphipods were exposed to spiked sediment concentrations that were time weighted averaged to yield 5.7, 10, 24, 38, and 97 mg a.i/L.  On Day 28, survival was statistically significant (p<0.05) in the three highest treatment concentrations when compared to the negative control.  These treatment concentrations were excluded from the Day 28 dry weight analysis and there were no significant reductions from the negative control in the two lowest treatment concentrations.  On Day 35, survival was significantly reduced (p<0.05) at all but the lowest treatment concentration as compared to the negative control.  The number of offspring per female had significant (p<0.05) at all but the lowest treatment concentration when compared to the negative control.  On Day 42, survival was significantly reduced (p<0.05) when compared to the negative control at the three highest treatment concentrations.   These three concentrations were excluded from further statistical analysis for Day 42 dry weights, number of offspring per female, and male to female ratio endpoints.  For Day 42 dry weights, number of offspring per female, and male to female ratio, there were no significant (p<0.05) effects at the two lowest treatment concentrations when compared to the negative control.  On the basis of sediment dry weight and pore water, the NOAECs from this study are 5.7 mg/kg dw sediment and 0.5 mg a.i/L, respectively for the most sensitive endpoints which are Day 35 survival, Day 35 number of offspring per female and Day 42 survival.  This study is classified as acceptable.

Results from the chronic study on C. riparius indicate a much lower NOAEC for this species compared to the chronic study with amphipod (<101 ug a.i/kg sediment for midge vs. 5700 ug a.i./kg sediment for amphipod).  This lower NOAEC likely reflects a combination of factors including interspecies differences in sensitivity to fenpyrazamine and measurement of additional endpoints (e.g., development rate).  It is important to note, however, that this study involved exposure via the overlying water and concentrations varied considerably over time.  Specifically, both pore water and sediment concentrations increased dramatically from day 0 to day 28, while overlying water concentrations decreased, thus reflecting the expected partitioning of fenpyrazamine to sediments from the water column.  Freshwater midges were exposed to time weighted averaged sediment concentrations of 101, 215, 326, 611, and 790 ug a.i/kg dw sediment.  Percent emergence was significantly reduced (p<0.05) at the two highest treatment concentrations as compared to the negative control.  The combined male and female development rate was significantly reduced (p<0.05) at the two lowest and two highest treatment concentrations.  Although the test guideline followed in this study (OECD 219) is designed to mimic a spray drift event, a study that uses spiked sediment, simulating a runoff or erosion event is preferred.  OCSPP test guidelines recommend that sediments be equilibrated with test compound prior to testing.  This study is classified as supplemental for this reason as well as the fact that a definitive NOAEC was not achieved for the most sensitive endpoint of this study.  For risk assessment purposes, a toxicity value of 101 ug a.i/L will be used for estimating chronic risk quotients for freshwater benthic invertebrates in the sediment and 20 ug a.i/L for freshwater benthic invertebrates in the pore water (i.e., an upper bound of 101 ug a.i/kg dw sediment and 20 ug a.i/L will be assumed as a screen for chronic effects).

The effects of fenpyrazamine on the saltwater amphipod, Leptocheirus plumulosus, were examined in a 28-d spiked sediment exposure study (MRID 48400008).  Time weighted average concentrations of 3.0, 6.3, 12, 25, and 50 mg a.i/kg dw sediment in addition to solvent and negative controls. Survival was significantly reduced (p<0.05) at the two highest treatment concentrations as compared to the negative control.  The number of offspring per female was significantly reduced (p<0.05) at the 12 mg a.i.kg dw sediment treatment concentration when compared to the negative control.  For mean dry weight, there were significant reductions (p<0.05) at all three treatment concentrations that were not excluded from the analysis due to effects on survival.  The resultant NOAEC and LOAEC for this study was <3 and 3 mg a.i/kg dw sediment based on effects to dry weights.  The corresponding NOAEC and LOAEC for pore water concentrations is <0.25 and 0.25 mg a.i/L.  This study was classified as supplemental as it does not achieve a definitive NOAEC for the most sensitive endpoint of the study.    For risk assessment purposes, a toxicity value of 3 mg a.i/kg dw sediment will be used for estimating chronic risk quotients for estuarine/marine benthic invertebrates in the sediment and 0.25 mg a.i/L for estuarine/marine benthic invertebrates in the pore water (i.e., an upper bound of 3 mg a.i/kg dw sediment and 0.25 mg a.i/L will be assumed as a screen for chronic effects).
   *                         Vascular and Non-vascular Aquatic Plants

One vascular aquatic plant study (MRID 48400018) was submitted along with three non-vascular aquatic plant studies (algae) were submitted conducted with TGAI fenpyrazamine (MRIDs 48400021, 48400022, 48400023, and 48400024).

In the aquatic vascular plant toxicity study, Lemna gibba (duckweed) was exposed to mean measured treatment concentrations ranging from 0.023 to 5.9 mg a.i/L.  The percent growth inhibition in the treated culture as compared to the negative control ranged from -11 to 79% based on frond density, 1 to 90% based on frond weight, and 5 to 55% based on days 0 to 7 growth rate.  Fronds in the two highest treatment groups were smaller and had reduced root development relative to the negative control.  There were no other morphological abnormalities noted in the negative control or any other treatment concentrations.  The most sensitive endpoint for this study was frond weight with a 96-h EC50 and NOAEC value of 1.1 and 0.060 mg a.i/L, respectively.  This study is classified as acceptable.  For risk assessment purposes, a toxicity value of 1.1 mg a.i/L will be used to assess risk to non-listed aquatic vascular plants while a value of 0.060 mg a.i/L will be used to assess risk to listed aquatic vascular plants.

Four acceptable studies with aquatic non-vascular plants (algae) were submitted with TGAI fenpyrazamine (94.7  -  98.8% % purity).  In one study conducted with freshwater green algae (Pseudokirchneriella subcapitata, MRID 48400021), fenpyrazamine was exposed to cultures ranging from 0.053 to 0.90 mg a.i/L, mean measured concentrations.  The percent growth inhibition in the treated algal culture as compared to the negative control ranged from 26 to 95% based on cell density, 5 to 48% based on growth rate, and 15 to 92% based on biomass.  At test termination, cells at the highest treatment concentration were observed to be bloated while cells in the negative control and remaining treatment concentrations appeared normal.  The most sensitive endpoint was cell density with 96-h EC50 and NOAEC values of 0.16 and <0.053 mg a.i/L, respectively.  As the NOAEC for this endpoint was non-definitive, EFED policy is use the EC05 in place of the NOAEC for this endpoint, which was determined to be 0.029 mg a.i/L.

In an acceptable study with the marine diatom Skeletonema costatum (MRID 48400022), TGAI fenpyrazamine was exposed in mean measured concentrations of 0.0045, 0.011, 0.028, 0.18, 0.42, and 1.2 mg a.i/L to cultures.  The percent growth inhibition in the treated algal culture as compared to the negative control ranged form 3 to 97% based on cell density, the most sensitive endpoint.  Cells in the negative control group and all treatment concentrations appeared normal throughout the duration of the test.  The 96-h EC50 and NOAEC values for this test (based on cell density) are 0.027 and <0.0045 mg a.i/L.  As the NOAEC for this endpoint was non-definitive, EFED policy is use the EC05 in place of the NOAEC for this endpoint, which was determined to be 0.002 mg a.i/L.

In an acceptable study with the freshwater diatom Navicula pelliculosa, (MRID 48400023), TGAI fenpyrazamine was exposed in mean measured concentrations of 0.0049, 0.012, 0.030, 0.074, 0.019, and 0.47 mg a.i/L to cultures.  The percent growth in the treated algal culture as compared to the negative control ranged from -11 to 99% based on cell density, the most sensitive endpoint.  Cells in the negative control group and all treatment concentrations appeared normal throughout the duration of the test.  The 96-h EC50 and NOAEC values form this test (based on cell density) are 0.011 and 0.0049 mg a.i/L, respectively.

A study conducted with TGAI fenpyrazamine on the cyanobacteria Anabaena flos-aquae (MRID 48400024) exposed cultures to mean measured concentrations of 0.045, 0.12, 0.28, 0.74, 1.8, and 4.6 mg a.i/L.  The percent growth inhibition in the treated algal culture as compared to the negative control ranged from 12 to 87% based on cell density, the most sensitive endpoint.  Cells in the negative control and treatment concentrations appeared normal throughout the duration of the study.  The 96-h EC50 and NOAEC values (based on cell density) were 1.2 and 0.74 mg a.i/L. This study is classified as acceptable. For risk assessment purposes, a toxicity value of 0.011 mg a.i/L will be used to assess risk to non-listed aquatic non-vascular plants while a value of 0.0049 mg a.i/L will be used to assess risk to listed aquatic non-vascular plants.

Additionally, two acceptable aquatic non-vascular plant toxicity studies were submitted with degradation products of fenpyrazamine.  Both studies were acceptable and exposed degradation products to the freshwater green algae Pseudokirchneriella subcapitata.  In one study with S-2188-DC (100% purity) green algae cultures were exposed to mean measured concentration is 1.6, 3.0, 6.0, 13, 24, 47, and 98 mg a.i/L.  The percent growth inhibition in the treated algal culture as compared to the negative control ranged from 1.1 to 89.3 % based on cell density, 0.3 to 22.6% based on growth rate, and 1.1 to 57.6% based on biomass.  Aggregation was observed in the three highest treatment concentrations.  There were no morphological abnormalities observed in any treatment concentration throughout the 96-hour exposure period.  The EC50 and NOAEC values (based on cell density) are 32 and 1.6 mg a.i/L, respectively.

In another study conducted with Pseudokirchneriella subcapitata, the fenpyrazamine degradate S-2188-OH (98.4% purity) was exposed to cultures at mean measured concentrations of 1.6, 3.1, 6.3, 13, 25, 48, and 99 mg a.i/L.  The percent growth inhibition in the treated algal culture compared to the negative control ranged from -2.3 to 72% based on cell density, -0.37 to 20% based on growth rate, and -1.2 to 66% based on biomass.  Aggregation was observed in the three highest treatment concentrations.  There were no morphological abnormalities observed in any treatment concentrations throughout the 96 hour exposure period.  The EC50 and NOAEC values based on cell density were 55 and 3.1 mg a.i/L, respectively.

                     4.4.1 Terrestrial Effects

All toxicity reference values used to assess the potential acute and chronic risks of fenpyrazamine exposure to birds and mammals were obtained from acceptable or supplemental studies using fenpyrazamine TGAI (Table 9).

Table 9.  Toxicity Reference Values For Terrestrial Organisms Exposed To Fenpyrazamine.
                               Exposure Scenario
                                     % A.I.
                                    Species
                                      Dur.
                           Toxicity Reference Value
                                    (95% CL)
                                  Effect Notes
                                     MRID;
                                Classifi-cation
 Avian Toxicity
                                     Acute
                                  TGAI   98.8%
 Canary  Serinus canaria
 (Acute Oral)
                                      14 d
 LD50 >2000 mg a.i/kg bw (95% CI not available)

   * No mortalities in control or at the 2000 mg a.i/kg bw treatment concentration
   * No clinical signs of toxicity or sublethal effects were observed
                              48400010 Acceptable
                                     (2010)

                                  TGAI   97.7%
 Mallard Duck Anas platyrhynchos
 (Subacute, Dietary)
                                      8 d
 LC50 >4430 mg a.i/kg diet (95% CI not available)
   * Five mortalities were observed during the study, three in the 2360, and two in the 4430 mg a.i/kg diet treatment concentrations, mean measured
   * Group body weight gain was significantly reduced (p<0.05) at the 4430 mg a.i/kg diet
                              48400012 Acceptable
                                     (2006)

                                  TGAI   94.7%
 Bobwhite Quail Colinus virginianus
 (Acute Oral)
                                      14 d
 LD50 >2000 mg a.i/kg bw
 Probit slope: N/A
   * No mortalities in control or at the 5000 mg/kg test level.
   *  No clinical signs of toxicity or sublethal effects observed at all treatment concentrations
                             48400009   Acceptable
                                     (2006)

                                  TGAI   94.7%
 Bobwhite Quail Colinus virginianus
 (Subacute Dietary)
                                      8 d
 LC50: >5039 mg a.i/kg diet (95% CI not available)

   * The only mortality in the study occurred in the highest treatment concentration (5039 mg a.i/kg diet, mean measured)
   * Group body weight gain was significantly reduced (p<0.05) at the two highest treatment levels (2687 and 5039 mg a.i/kg diet)
   * Clinical sings of toxicity included wing droop and lethargy which were observed in two birds in the highest treatment concentration, one of which later died, representing the single mortality in the study
                                    48400011
                                   Acceptable
                                     (2006)
                                                                        Chronic
                                  TGAI   94.7%
 Mallard Duck Anas platyrhynchos
                                     22 wk
 NOAEC=517 mg a.i/kg diet
 LOAEC=1022 mg a.i/kg diet

   * One adult mortality was observed during the test
   * No clinical sings of toxicity, effects on food consumption, or effects on reproductive parameters were observed at any treatment concentration during the test
   * 14-day survivor body weight in the 1022.3 mg a.i/kg diet treatment concentration (the highest tested) was significantly reduced (p<0.05) from the control)
                                    48400013
                                   Acceptable
                                     (2008)

                                  TGAI   94.7%
 Bobwhite Quail Colinus virginianus
                                     24 wk
 NOAEC= 248 mg a.i/kg diet
 LOAEC=495 mg a.i/kg diet

   * Three adult mortalities although post mortem analysis showed they may not have been chemical related
   * There were significant (p<0.05) reductions in adult female body weight gain at the 495 mg a.i/kg diet test concentration
                              48400014 Acceptable
                                     (2008)
 Mammals
                                     Acute
 TGAI
 94.8%
 Rat
 (Rattus norvegicus)

 14 d
 LD50 >2000 mg ai/kg bw (females)

   * No mortality occurred in the study
   * No abnormal clinical sings of toxicity were evident
   * One anima had fluid retention in the uterus at post mortem not considered to be treatment related

                                    48400106
                                   Acceptable
                                     (2007)
 Chronic
 TGAI
 94.7%
 Rat
 (Rattus norvegicus)

 2 gen
 NOAEL = 1000 ppm
 LOAEL = 3000 ppm
   * There were no treated related mortalities or clinical signs of toxicity in any generation
   * In the parental generation and F1 generation, there were no significant (p<0.05) differences in body weight gain
   * There was a statistically significant decrease (p<0.05) in food consumption of parental females during pre-mating and gestation of the highest treatment level
   * There were no effects on oestrus cycle, number of pairs mating, time to mating, number of females becoming pregnant, or the length of gestation in the P and F1 generation parents
   * Mean pup weight of F1 pups at birth and 21 days post partum was significantly lower (p<0.05) in the highest treatment level
   * There was a significant reduction (p<0.05) in the mean number of implantations per dam and litter size, and a statistically significant increase in post implantation loss.

 48400127
 Acceptable
 (2009)
 Nontarget Insects - Bees
                                     Acute
                                  TGAI   94.7%
 Honeybee  Apis mellifera
 (Acute contact toxicity)
                                      48 h
 LD50: > 100 ug ai/bee (95% CI N/A)
 Probit slope: N/A
   * Mortality was 0, 3.3, 13.3, 6.7, 13.3, and 26.6% at the 1.9, 4.3, 9.4, 21, 45, and 100 ug a.i/bee treatment concentrations
   * Mortality in the negative and solvent controls was 10% and 3.3%, respectively.

                                    48400015
                                   Acceptable
                                     (2006)

                                  TGAI   97.6%
 Honeybee        Apis mellifera
 (Oral toxicity study)
                                      48 h
 LD50: > 100 ug ai/bee (95% CI N/A)
 Probit slope: N/A
   * Mortality was 10, 6.7, 3.3, 23, 20% at the 6.3, 13, 25, 50, and 100 ug a.i/bee
   * Mortality in negative and solvent controls was 0%.
                                    48399935
                                  Supplemental
                                     (2006)
 Other Non-target Terrestrial Organisms
                                     Acute
                                   TGAI 94.7%
                           Earthworm (Eisenia fetida)
                                      14 d
 LC50: >800 mg a.i/kg dw soil
 NOAEC (body weight): 25 mg a.i/kg soil

   * Mortality was 0, 0, 0, 0, 0, 2.5, 7.5, and 2.5 % at the negative control, solvent control, and the 25, 50, 100, 200, 400, and 800 mg a.i/kg soil concentrations
   * Body weight was significantly reduced (p<0.05) at all but lowest concentration

                                   48400025
                                  Supplemental
                                     (2006)
 Terrestrial Plant
                               Seedling emergence

                                      TEP
                                     44.4%

                                Multiple species

                                      21 d
 Most sensitive monocot: corn
 EC25 (survival): >1.54 lbs a.i/A (95% CI:  N/A)
 Slope : 2.97

 NOAEC: 0.15 lbs a.i/A
 -----------------------
 Most sensitive dicot, flax
 EC25 (weight): >0.53 lbs a.i/A (95% CI: N/A)
 Slope: 5.31

 NOAEC: <0.035 lbs a.i/A

   * The percent inhibition to seedling emergence in the treated species compared to negative control ranged from -20  -  27.6%
   * Phytotoxic effects included necrosis, leaf curl, stem curl, and unshed seed coat.
   * Corn was most sensitive monocot based on effects to survival
   * Flax was most sensitive dicot based on effects to biomass (weight)

                                    48400016
                                  Supplemental
                                     (2010)
                                Vegetative vigor

                                      TEP
                                     44.4%

                                Multiple species

                                      21 d
 Most sensitive monocot
 EC25: Could not be determined due to lack of toxicity
 NOAEC: 0.56 lbs a.i/A
 -----------------------
 Most sensitive dicot
 EC25: Could not be determined due to lack of toxicity
 NOAEC: 0.56 lbs a.i/A

   * The % survival in all species was not significantly affected and the % inhibition of survival ranged from  to 4.2%.
   * Phytotoxic effects included necrosis, leaf curl, stem curl, and unshed seed coat.
   * Length (height) and weight endpoints were not significantly affected at any treatment concentration for any species.

                                    48400017
                                  Supplemental
                                     (2010)
Bolded values refer to the most sensitive endpoint for a given taxa to be used in quantitative risk assessment.

                        *                         Birds (Acute Toxicity)

Acute oral and subacute dietary toxicity studies are available for three avian species (northern bobwhite quail, mallard duck, and canary) in three orders (Galliformes, Anseriformes, Passeriformes).  Overall, these studies indicate that fenpyrazamine is practically non-toxic to these species of birds on an acute exposure basis.  The acute oral LD50 values are > 2000 mg a.i/kg bw for both the northern bobwhite quail and canary studies (MRIDs 48400009 and 48400010, respectively) since no treatment-related mortality occurred at the highest dose tested.  Furthermore, there were no treatment-related sublethal signs of toxicity (body weight, food consumption) were reported in these studies.  In the canary study within the first hour of dosing, 3 birds regurgitated at the limit dose.  However, these birds were immediately replaced and none of the remaining birds regurgitated or showed other sublethal signs of toxicity.  Therefore, the study validity is not considered to be impacted by this low rate of regurgitation.  All three acute oral studies are classified as acceptable.   For risk assessment purposes, an acute oral LD50 of > 2000 mg a.i/kg bw) for passerines will be used qualitatively to evaluate potential acute effects to birds (i.e., a lower bound of 2000 mg a.i/kg bw will be assumed as a screen for acute effects).

There were two subacute studies submitted for the northern bobwhite quail and mallard duck (MRIDs 48400011 and 48400012, respectively).  In the northern bobwhite quail study, TGAI fenpyrazamine was exposed in the diet at mean measured concentrations of 306.9, 628.1, 1318, 2687, and 5039 mg a.i/kg diet.  There was a single mortality that occurred at the highest treatment concentration.  The bird displayed wing droop and lethargy prior to death.  There were no other clinical signs of toxicity that were observed during the test.  Mean body weight gain in the three highest treatment concentrations was significantly lower (p<0.05) as compared to the negative control.  There were no treatment related effects on food consumption noted.  The resultant LC50 for the study was >5039 mg a.i/kg-diet and this study was classified as acceptable.

For the mallard duck study, TGAI fenpyrazamine was administered in the diet at 291 568, 1210, 2360, and 4430 mg a.i/kg-diet (mean measured concentrations).  There were a total of five mortalities that occurred during the study, three birds at the 2360 and two birds at the 4430 mg a.i/kg-diet treatment concentrations.  There were no clinical signs of toxicity noted during the study.  The mean body weight gain was significantly lower (p<0.05) at the highest treatment concentration compared to the negative control.  There were no treatment related effects on food consumption noted during the study.  The resultant LC50 for this study was >4430 mg a.i/kg-diet and this study is classified as acceptable.  For risk assessment purposes, a subacute dietary  LC50 of > 4430 ppm in the diet) will be used qualitatively to evaluate potential acute effects to birds (i.e., a lower bound of 4430 ppm will be assumed as a screen for acute effects).

                        *                         Birds (Chronic Toxicity)

Two studies were submitted that examined the chronic toxicity of fenpyrazamine to avian species.  In the study with mallard duck (MRID 48400013) fed 26 week old mallards (4 groups of 16 replicate pairs/group including control) approaching their first breeding season a diet containing 258, 517 or 1000 mg a.i/kg-diet of TGAI fenpyrazamine (94.7%i). There was a single adult mortality observed during the test from the control group that was found dead approximately 19 weeks post treatment.  There were no overt clinical signs of toxicity observed at any of the treatment concentrations nor were there any treatment related effects on adult body weight or food consumption.  Mean 14-day survivor body weight was significantly reduced (p<0.05) in the highest treatment concentration as compared to the negative control.  The study author did not consider this to be a treatment related effect, citing one reason as a failure to detect a similar effect in the companion northern bobwhite quail study (MRID 48400014).  The study reviewer however did find evidence of a treatment related effect for this endpoint and therefore could not dismiss the effects observed in this study.  Aside from this effect on 14-day survivor body weight, there were no other statistically significant treatment related effects on any reproductive parameters at any treatment concentration.  The resultant NOAEC and LOAEC for this study were 519 and 1022 mg a.i/kg-diet, respectively based on 14-day survivor body weight and the study is classified as acceptable.

In the study with the northern bobwhite quail (MRID 48400014) fed 28 week old quail (4 groups of 18 replicate pairs/group including control) approaching their first breeding season a diet containing mean measured concentrations of  248, 495, and 978 mg a.i/kg-diet of TGAI fenpyrazamine (94.7%). There were three adult mortalities that occurred during the study, none of which were considered treatment related.  There were no overt clinical signs of toxicity observed at any of the treatment concentrations.  There were no significant reductions in hatchling body weight, however there was a slight significant reduction (p<0.05) of 14-day survivors at the 495 mg a.i/kg-diet treatment concentration.  There were no other statically significant effects on any other reproductive parameter at any treatment concentration.  The resultant NOAEC and LOAEC for this study was 248 and 495 mg a.i/kg-diet, respectively, based on 14-day survivor body weight and the study is classified as acceptable.  The dietary chronic NOAEL of 248 ppm will be used in estimating chronic risk quotients to avian species.

                        *                         Mammals (acute toxicity)