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

OFFICE OF CHEMICAL SAFETY AND POLLUT I ON PREVENTION


### MEMORANDUM

DATE:

SUBJECT:

FROM:

THRU:

TO: February 6, 2014

Registration Review

- Preliminary Problem Formulation for the Ecological Risk
Assessment and Drinking Water Exposure Assessment to be conducted for
Fenamidone (PC Code 046679; DP Barcode 417865)

James K. 

### Wolf, Ph.D., Soil Scientist

# ~ f(LJvfJ

Katherine R. Stebbins, Biologist

## ~ Environmental Risk Branch 3
Environmental Fate and Effects Division (7507P)

Rosanna Louie-Juzwiak, RAPL. 

## /7) "-

# DanaSpatz,Ch~ 

# g

Environmental Risk Branch 3**U~** 

### Environmental Fate and Effects Division (7507P

Christina Scheltema, Chemical Review Manager
Patricia Parrott, Chief
Risk Management and Implementation Branch 3
Pesticide Reevaluation Division (7508P)

The Environmental Fate and Effects Division (EFED) has completed the preliminary problem
formulation (attached) for the ecological risk and drinking water exposure assessments to be
conducted as part of the Registration Review ofthe fungicide fenamidone (PC Code 046679).
This document is intended to provide an overview of what is currently known regarding the
environmental fate and ecological effects associated with fenamidone and its degradation products, and outlines uncertainties regarding attributes ofthe parent compound and its
transformation products

. It 

### describes the preliminary ecological risk hypothesis and the processes that will be used during the completion of the preliminary ecological risk assessment in support of Registration Review.

As noted in Section 5

, the database for environment?! fate and transport for fenamidone is
sufficient for risk assessment such that, with the exception of an independent laboratory method
for water, no additional data are anticipated to be required at this time. With regard to the ecological effects database, two additional studies are anticipated to be required for the registrat i on review risk assessment (an acute toxicity test for the fathead minnow and a vegetative vigor toxicity test)

. Please refer to this section for additional details.

1

### 2 INTRODUCTION

Fenamidone is registered for use as a broad spec trum fungicide for control of certain pathogenic fungal diseases in a variety of crops including potatoes and othe r tuberous and corm vegetables, tomatoes, onions and other bulb vegetables, root vegetables, grapes, turnip greens, okra, coriander, lettuce, leafy vegetables, brassica ve getables, tobacco, fruiti ng vegetables, carrots, cucurbit crops, ornamentals, cotton and sunflower.

Fenamidone belongs to the imidazole chemical fa mily of fungicides, which includes iprodione and cyazofamid. Fenamidone is classified as a “Qui none outside Inhibitor” (QoI), which inhibits mitochondrial respiration by blocking electron transfer at the Comp lex III level in several plant pathogenic fungi species.

The chemical structure of fenamidone and se veral chemical identifiers are provided in Table 1

.

Table 1. Fenamidone Chemical Identifiers

Chemical Name 

### (+)-(4 S )-4-Methyl-2-methylthio-4-phenyl-(1H)-1- phenylamino-2- imidazolin-5-one

Chemical Structure

Chemical Abstracts Service (CAS) Registry Number 161326-34-7

Smiles Code [C@@]1(C(=O)N(C(=N1)SC)NC2=CC=CC=C2)C3=CC=CC=C3



### Fenamidone may be applied as an aqueous broad cast treatment via ground, chemigation or aerial equipment for a variety of terrestrial agricultu ral crops. Additionally, fenamidone may be applied as a soil in-furrow application for cotton, as a pre-plant soil incor poration application for tobacco, and also as a slurry or mist for seed tr eatments (for sunflowers and cotton). In addition to the uses for terrestrial crops, fenamidone may also be applied to commercially grown ornamentals (in green/saran houses only) through pr essurized drench (flood), sprinkler, and drip irrigation systems.

There are two end-use products, Reason ® 

### 500 SC (EPA. Reg. No. 264-695) and FENSTAR ® 

### (EPA Reg. No. 432-1389), and both are formulated as a soluble concentrate containing 44.4% fenamidone as the single active ingredient with 4.13 pounds of fenamidone per gallon (U.S.) of product. An overview of the registered uses of fenamidone is provided in Table 2. Note that the

### 3 application rates included on the currently regi stered labels are on a per season basis. The number of applications of fena midone that can be applied per calendar year on a given field is not explicitly stated on current labels. As such, se veral of the currently re gistered uses may result in multiple seasonal applications of fenamidone per year.

Fenamidone was first registered in 2002. Accord ing to the Biological and Economic Analysis Division Report 1

, 

### agricultural use has st eadily increased during th e 2005-2011 time period (use was not reported from 2002-2004). On averag e, 23,000 pounds of fenamidone were applied annually to 106,000 acres, at an av erage application rate of 0.2 pounds of active ingredient per acre (lb. a.i./acre). The maximum single applicat ion rate ranges from 0.177 to 0.26 lb a.i./acre (Table 2). The crops with the highest use (in pounds a.i. applied and acres treated) are lettuce, carrots, and potatoes, which is c onsistent with the regional use be ing highest in California, Idaho,
and Arizona.

Usage data are not available for the commercial applications to ornamentals or for the seed
treatments for cotton and sunflowers.

1 Yourman, L., Alsdek, J. Berwald, D. BEAD Chemical Profile for Registration Review: Fenamidone. Sept. 18,
2013.4Table 2. Registered FenamidoneUses and Application RatesCrop/Site Residential Agricultural Forestry(Timing) andApplicationTypeMethod/EquipmentMaximumSingleApplicationRate byFormulation(lb a.i./A)MaximumApplication RateMaximumApplicationNumber PHI (days) REI (hours) MRI (days) Geographic RestrictionsCommentsPer Yearlb a.i./APer CClb a.i./APerYeariPerCCBrassica(Cole) leafyvegetablesand turnipgreensa(Foliar)Aerial,Ground,ChemigationAircraft,ground,irrigation0.264 NS 0.793 NS 3h2 12 5 NSBulbvegetablesb(Foliar)Aerial,Ground,ChemigationAircraft,ground,irrigation0.177 NS 0.709NS 4h7 12 5 NSCarrot(Foliar)Ground,ChemigationDirectedspray,irrigation0.264 NS 0.793 NS 3h14 12 14 NSCottonAt planting(soil in furrow)Ground0.00001452lb / linear ftNS 0.264 NS NS NS 12 NS NSSeed trt.Mist or slurryseed treater0.00050002lb / lb of seedNS NS NS NS NS NS NS NSBased on a seeding rate of18.89 pounds of seed/A2, theapplication rate converts to0.009445 lb a.i./ACucurbitc(Foliar)Aerial,Ground,ChemigationAircraft,ground,irrigation0.177 NS 0.709NS 4h14 12 5 NSGrapes(Foliar)Aerial,Ground,ChemigationAircraft,ground,irrigation0.0871 NS 0.261 NS 3h30 12 10 NS East of the RockiesLeafyvegetables(exceptbrassica)d(Foliar)Aerial,Ground,ChemigationAircraft,ground,irrigation0.264 NS 0.793 NS 3h2 12 5 NS2Becker, Jonathan and Ratnayake, Sunil. Acres Planted per Day and Seeding rates of Crops Grown in the United States. 2011. Biological and Economic AnalysisDivision (BEAD) Office of Pesticide Programs. United States Protection Agency5Crop/Site Residential Agricultural Forestry(Timing) andApplicationTypeMethod/EquipmentMaximumSingleApplicationRate byFormulation(lb a.i./A)MaximumApplication RateMaximumApplicationNumber PHI (days) REI (hours) MRI (days) Geographic RestrictionsCommentsPer Yearlb a.i./APer CClb a.i./APerYeariPerCCPotatoes andotherTuberous andCorme(Foliar)Aerial,Ground,ChemigationAircraft,ground,irrigation0.264 NS 0.793 NS 3h14 12 5 NSTomatoes,peppers andother fruitingvegetables(exceptcucurbits)f(Foliar)Aerial,Ground,ChemigationAircraft,ground,irrigation0.264 NS 0.793 NS 3h14 12 5 NSRootvegetables(exceptcarrot,potato, radishandsugarbeet)g(Foliar)Aerial,Ground,ChemigationAircraft,ground,irrigation0.264 NS 0.793 NS 3h14 12 14 NSSunflowerSeed trt.Mist or slurryseed treater0.00187104lb / lb of seedNS NS NS NS NS NS NS NSBased on a seeding rate of 4.0lbs of seed/A3, the applicationrate converts to 0.007484 lbsa.i./ATobacco(Pre-plantand Foliar)Aerial,Ground,ChemigationSoil inc.,aircraft,ground,irrigation0.264 NS 0.793 NS 3h30 12 5 NSOrnamentals(Greenhouseand saranhouse useonly)DrenchFlood, Drip,Sprinkler49.17* NS NS NS 4 NS 12 NS NS*Apply 14 fl oz of product to400 sq.feet(Foliar)Ground,Chemigation1.806 NS NS NS 2 NS 12 NS NS3Becker, Jonathan and Ratnayake, Sunil. Acres Planted per Day and Seeding rates of Crops Grown in the United States. 2011. Biological and Economic AnalysisDivision (BEAD) Office of Pesticide Programs. United States Protection Agency6Crop/Site Residential Agricultural Forestry(Timing) andApplicationTypeMethod/EquipmentMaximumSingleApplicationRate byFormulation(lb a.i./A)MaximumApplication RateMaximumApplicationNumber PHI (days) REI (hours) MRI (days) Geographic RestrictionsCommentsPer Yearlb a.i./APer CClb a.i./APerYeariPerCCaBroccoli, Broccoli (Chinese, gai lon), Broccoli raab (rapini), Brussels sprouts, Cabbage, Cabbage Chinese (bok choy),Cabbage Chinese (Napa), Cabbage Chinese mustard (gai choy), Cauliflower, Cavalobroccolo, Collards, Kale, Kohlrabi,Mizuna, Mustard greens, Mustard spinach, Rape greens), Turnip greensbChive, fresh leaves; chive, Chinese, fresh leaves; daylily,bulb; elegans hosta; fritillaria, bulb; fritillaria, leaves; garlic, bulb; garlic, great-headed, bulb; garlic, serpent, bulb; kurrat; lady’s leek; leek; leek, wild;lily, bulb; onion, Beltsville bunching; onion, bulb; onion, Chinese, bulb; onion, fresh; onion, green; onion, macrostem; onion,pearl; onion, potato, bulb; onion, tree,tops; onion, Welsh, tops; shallot, bulb;shallot, fresh leaves; cultivars, varieties, and/or hybrids of these.c.Chayote, chinese waxgourd, citron melon, cucumber, gherkin, edible gourds, momordica spp., muskmelon, pumpkin, squash (summerand winter) and watermelondAmaranth (leafy amaranth, Chinese spinach, tampala), Arugula (roquette), Cardoon,Celery, Chinese celery, Celtuce, Chervil, Chrysanthemum (edible-leaved), Chrysanthemum (garland), Cilantro, Cornsalad, Cress (garden), Cress (upland), Dandelion, Dock (sorrel), Endive (escarole),Fennel florence (finochio), Lettuce (head and leaf), Orach, Parsley,Purslane (garden),Purslane (winter), Radicchio (redchicory), Rhubarb, Spinach, Spinach New Zealand, Spinach vine (Malabar spinach, Indian spinach), Swiss chard)e.Arracacha, arrowroot, artichoke (Chinese),artichoke (Jerusalem), canna(edible), cassava (bitterand sweet), chayote (root),chufa, dasheen, ginger, leren, potato, sweetpotato, tanier, turmeric, yam (bean and true)fEggplant, Groundcherry, Okra, Pepino, Pepper (bell,chili, cooking, pimento, sweet), Tomatillo, Tomatog.Beet (garden), Burdock (edible), Celeriac, Chervil (turnip-rooted), Chicory, Ginseng, Horseradish, Oriental Radish, Parsley(turnip-rooted), Parsnip, Rutabaga, Salsify (oyster plant), Salsify (black)Salsify (spanish), Skirret, TurniphMaximum number of applications not specified onlabel. Value derived by dividing the maximumseasonal rate by the maximum application rate.iFor all crops except Brassica and Leafy vegetables, the number of crop cycles per yearis assumed to be one. For Brassica andLeafy vegetables, two to three crop cycles per year may be assumed (dependingon the specific crop) in the absence of label information defining the number of applications per calendar year.

### 7 1. PREVIOUS RISK ASSESSMENTS

Previous Ecological Assessments

Several ecological risk assessments have been conducted for fenamidone uses in recent years [(New Chemical assessment-lettu ce, 10/2/02), (New Use-potatoes, tuberous and corm, lettuce, tomatoes, cucurbits, bulb vegetables and orna mentals, 7/16/04), (New Use-carrots, leafy vegetables, brassica, fruiting ve getables, and tobacc o, 6/14/07), and (New Use-grapes, root vegetables, and others crops, 7/ 6/09)]. EFED evaluated these assessments for fenamidone in
association with the current toxi city, exposure, and usage informa tion to determine if sufficient data are available and if further updates ar e needed to support re gistration review.

Based on previous assessments, there is the potentia l for risk to aquatic invertebrates from acute and chronic exposure and to fish from chronic e xposure. The previous asse ssments also identified a risk to listed non-vascular plants. There is also the potential for various indirect effects to nontarget animal species due to direct effects on the plant and animal community (for example, depletion of food sources and habitat). The major conclusions presented in the previous chemical
assessments for fenamidone are summarized in Table 3 and are briefly discussed in the
subsections below.

Table 3. Summary of Risk Concer ns Identified for Fenamidone

Exposure

Basis Birds Mammals Terrestrial
Plants Terrestrial
Inverts. (honey

bee hazard) Fish Aquatic
Inverts Aquatic
Plants GroundwaterContamination Persistence Degradates of Concern

Acute No No No No No Yes a Yes b Yes c Yes c Yes c Chronic No No Yes a,d Yes a

a. At least one LOC has been exceeded in previous assessments
b. LOC exceedance for non-vascular, listed species.

c. Drinking Water
d. New data from a full life cycle study (MRID 48389201) is likely to result in a similar LOC exceedance



### All of the previously conducte d ecological risk assessments were based on modeling total fenamidone residues, which included six major transformation products 4 

### ; however, based on the available toxicity data for some of the degrad ates, the upcoming registration review assessment will be based on modeling the exposure for parent (fenamidone) alone (See Stressors of Concern section for more details). Additionally, previous assessments have not considered the potential for more than one crop cycle (or seas on) per calendar year. The regist ration review preliminary risk assessment may include modeling exposures for some crops to account for the multiple crop cycles or crop rotations that may occur within a given ca lendar year (See Table 2 footnotes). This is an
area where EPA will seek further information in a FOCUS meeting.

4 RPA-412636, RPA-412708, RPA-411639, RPA-413255, RPA-409446, RPA-410995

### 8 Previous Drinking Water Assessments

A drinking water assessment for fenamidone resi dues was conducted in 2007 [Hetrick, Termes and Whitby, 2007 5 

### ] to include the parent fenamidone and its transformation products using the total toxic residues (TTR) approac h. Based upon the recommendation fr om the Metabolism Assessment Review Committee (MARC) 6 

### , the following transformation products were included in the total toxic residues: RPA-412636, RPA-412708, RP A-411639, RPA-413255, RPA-409446, and RPA410995. Total fenamidone residues (or TTR) in surface source drinking water were 41.66 μg/L and 11.88 μg/L, the 1-in-10 year daily peak and annu al mean concentration, respectively, and 5.99 μg/L the 30-year annual mean concentrations. Based on SC I-GROW, the estimated total
fenamidone residue concentration in groundwater would not be exp ected to exceed 178 μg/L. The previous drinking water assessment was also ba sed upon one crop cycle (or season) per calendar

year.

Clean Water Act Programs

Fenamidone is not identified as a cause of impa irment for any water bodies listed as impaired under section 303(d) of the Clean Water Act. Tota l Maximum Daily Load (TMDL) criteria have not been developed for fenamidone. Aquatic benchmarks have not been established for fenamidone ( http://www.epa.gov/oppefed1/ecoris k_ders/aquatic_life_benchmark.htm ). Any data submitted or otherwise located as part of the regi stration review process ma y be used to establish aquatic life benchmarks, if applicable.

2. ENVIRONMENTAL FATE AND TRANSPORT

Physical and Chemical Pr operties of Fenamidone

A major chemical feature of fenamidone is the pr esence of a chiral carbon in the imidazole ring which gives rise to two enantiomers. The name fenamidone has been assigned exclusively to the Senantiomer, which is claimed to be the pesticide-active (eutomer) enantiomer.

The physicochemical properties of fenamidone are shown in Table 4 . Based on these properties alone, fenamidone is not expected to be volatile or to bioaccumulate.

Table 4. Selected Physical/Chemical 

### Parameters of Fenamidone

Parameter Value Source/Classification

Molecular formula C 17 H 17 N 3 OS MRID 45385702

Molecular Mass 311.4 g/mol MRID 45385702
Vapor pressure (20°C) 2.6 x 10 -9 torr MRID 45385711

Henry’s Law Constant (20  C) 1.37 x 10 -10 atm m 3 mole -1 Calculated

5 Hetrick, J.A., S.C. Termes, and K. Wh itby, 2007. Fenamidone. Drinking Water Assess ment for New Uses. DP Barcode D332878,

D316085, D316083, D339503. May 14, 2007.

6 TXR No. 0052287

### 9 Parameter Value Source/Classification

Aqueous solubility (20  C) 7.8 mg/L MRID 45385712
Log octanol-to-water partition coefficient (log K O W ) 2.8 MRID 45385713



### Environmental Fate Properties of Fenamidone

The environmental fate properties of fenamidone are summarized in Table 5 . Fenamidone is readily soluble (7.8 mg/L at 20°C) in water, an d degrades rapidly in soil to more persistent degradation/transformation products. The major route of degradation for fenamidone in the environment is biotransformation under aerobic conditions. Fenamidone is moderately mobile (average Koc = 388 mL/g oc 

### ) and appears to degrade faster in aer obic soils (half-lives 5 to 8 days) than in aerobic water-sediment systems (half-lives 67 to 128 days). Fenamidone is very stable in anaerobic sediments (half-lives > 1,000 days). In the environmental pH range of 5 to 9, fenamidone is stable towards abiotic hydrolysis . There are no major transformation products resulting from hydrolysis of fena midone over a period of 30 days ( i.e ., length of the study). Although direct photolysis occurred rapidly in laboratory studie s (half-lives 5 to 6 days) direct photolysis in natural water would be only significant in clear, shallow water. The role of indirect photolysis is not known. The results from the so il photodegradation study indicated no evidence of phototransformation on soil. The K oc 

### and K ow 

### indicate that fenamidone ma y partition to sediments. Partitioning to sediments was observed to increas e with time in the aerobic aquatic metabolism study. The terminal degradation product RPA-412636 observed in the aerobic soil metabolism, aerobic aquatic metabolism studies (a nd the terrestrial field dissipati on study) is more persistent (half-lives 105 to 462 days ) and mobile (average K oc 

### = 26 mL/g oc 

### ).

Table 5. Chemical Properties and Environm ental Fate Parameters of Fenamidone

Parameter Value Description Source (MRID)

Persistence

Hydrolysis half-life (25  C) pH 4: 42 days pH 5: stable (221.8 days) pH 7: stable (411.0 days) pH 9: 28 days Less than 10% degraded after 30 days @pH4: RPA-405862,
RPA-409344 @pH 9: RPA-409344 45385829

Aqueous photolysis half-life (25  C) 5.0, 5.8 days 45385830
45385831

Soil photolysis half-life (25  C) No evidence of phototransformations on soil DT50 greater for dark treatment compared to irradiated samples 45385832,
45385901

Aerobic soil metabolism half-life 4.8, 5.4, 8.1 days Degradates Major: RPA-717879,RPA-408056, RPA410914)

Minor: RPA-409446,RPA-410995, (RPA406012), RPA-405862 45385819
45385703

### 10 Parameter Value Description Source (MRID)
RPA-412636 Degradate
Aerobic soil metabolism ofdegradate S-enantiomer of RPA412636 (RPA-717879) 433.22, 105.0, 462.1 days No transformation products identified 45385820

Anaerobic aquatic metabolism halflife 1386.3 days 45400003

Aerobic aquatic metabolism halflife (25  C) 137. 8 days 45385821
45385822

Mobility
Freundlich soil-water partition coefficients (K F ); organic carbonnormalized Freundlich coefficients (K FOC ) mL/g; 2.43, 5.93, 6.93, 8.90, 4.93 mL/g OC ; 486, 494, 313, 387, 259 Avg. = 387.8 mL/g
oc 45385823



### a. Transformation Products

The proposed metabolic pathway in aerobic soil is shown in Appendix A Figure 1 . The proposed degradation pathways due to hydrolysis and photolysis in water are shown in Appendix A Figures
2 and 3 , respectively. The major, terminal metabolite is the cleavage product ( S )-Methyl-5- phenylimidazolidine-2,4-dione (RPA-412636). It can form in aerobi c soils and water-sediment systems, and is persistent (aerobic so il half-lives as long as 462 days) ( Table 5 ). The major degradate observed in the aerobic water-sedi ment systems was RPA-412636. In the aerobic soil metabolism studies the major transforma tion products were RP A-412636, RPA-411639, RPAField Dissipation

Terrestrial field dissipation half-life
and/or leaching depth 22.4 days (FL) 20.5 days (ND) 81.5 days (CA) 8.7 days (WA)

Fenamidone and transformation products RPA 406012, RPA 408056, RPA 409446, RPA 410914, RPA 410995 and RPA 717879 generally not detected
below 15 cm. Limited detections of RPA 717879
detected below 15 cm. Major Degr.: RPA-717879 (max of 10.4% of the total applied fenamidone

Minor Degr.: RPA-408056, RPA-410914, RPA-409446,RPA-406012, and-RPA410995 45385904

38.3 days (CA)

Fenamidone and its degradation products were generally not
detected below 15 cm. Major Degr.: None

Minor Degr.: RPA-717879, RPA-408056, RPA-406012,RPA-410914, and RPA409446 45385905



### Fish Bioconcentration

Fish bioconcentration factors (steady-state); depuration rate 

### - - No Data

### 11 413255, RPA-409446 and RPA-410995. The major tran sformation product observed in the aqueous photolysis study was RPA-412708 7 

### . The summary of degrada tion processes are found in
Table 7 , and the structures are shown in Appendix B

.

Batch equilibrium partition coefficients of se veral fenamidone transformation products are shown
in Table 6 . RPA-412636 (avg. Koc =26 mL/g oc 

### ) and its immediate precursor RPA-412708 (cleavage product; avg. Koc =31 mL/g oc 

### ) are very mobile 8 

### in soil. RPA-411639 and RPA-413255 are moderately mobile with average K oc 

### s of 611 and 458 mL/g oc 

### , respectively.

Table 6: Batch Equilibrium Coefficients fo r Four Fenamidone Degradation Products Degradate Code Sorption Coefficients K F / K
oc (mL/g; mL/g
oc ) Data Source (MRID)

RPA-412636 b 0.11, 0.43, 0.64; 0.32; 0.56
23, 36, 28, 17, 28 45385824

RPA-412708 a 0.26, 0.38, 0.40, 0.51, 0.65
52, 32, 21, 15, 33 45385825

RPA-411639 3.17, 6.6, 18.48, 14.89, 8.96
634, 347, 543, 784, 746 45385826

RPA-413255 3.16, 7.46, 4.97, 11.07, 9.01
632, 622, 261, 326, 450 45385827

a also referred to as RPA-412108 in some EFED documents.

b The batch equilibrium partition coefficient for RPA-412636 will be used to represent mobility of total fenamidone residues.



### In terrestrial field dissipati on studies conducted in California, Florida, North Dakota, and Washington, most residues were not found below 15 cm (shallowest sampling depth). However, at the Florida site, fenamidone was detected to a depth of 30 cm (0.007 mg/g) and the degradation product RPA-717879 (the S-isomer is RPA-412636) wa s detected down to 75 cm 0.006 mg/g). At the California site, RPA-717879 was detected at qu antifiable concentrations down to 30 cm (max. 0.009 mg/g).

Throughout this document, fenamidone and its transformation products ( Table 7 ) are named by the company code assigned only to the S- enantiomer. The company code for fenamidone is RPA407213.

7 Some documents have listed this degradate as RPA-412108.

8 EFED Standardized Soil Mobility Classi fication Guidance; April 21, 2006. Memorandum From S. Bradbury to Environmental
Fate and Effects Division. Environmental Fate and Effects Division. Office of Pesticide Programs. United States Environmental Protection Agency.

### 12 Table 7. Metabolite Company Code (ID), Chemic al Names, Degradation Process and Study where Degradate was observed and Structures.

Transformation
Product a
S-enantiomer (racemic mix) Chemical Name Degradation Process and Study where observed

RPA-412636 (RPA-717879) ( S )-Methyl-5-phenylimidazolidine-2,4-
dione CAS Reg. No. 27539-12-4 Cleavage of the -N-N- bond of fenamidone and elimination of the methylthio group Aerobic soil metabolism, aerobic water-sediment systems, terrestrial field dissipation studies ASM: 35% Aerobic Aquatic: 7.8%
RPA-412708 (RPA-408056) (5 S )-3,5-dihydro-5-methyl-2- (methylthio)-5-phenyl-4 H -imidazole-4-

one CAS Reg. No. 332855-82-0 Cleavage of the -N-N- bond of fenamidone. This metabolite may be considered as the immediate precursor to RPA-412636 Aerobic soil metabolism, aerobic water-sediment systems, hydrolysis (pH 4; 9), photolysis studies Aquatic photolysis: 35.6% Soil photolysis: 16.8-19.5% ASM: 17.3% Aerobic aquatic: 23.8%
RPA-411639 (RPA-406012) (5 S )-3,5-5-methyl-2-(methylthio)-3-[(4- nitrophenyl)amino]-5-phenyl-4 H

imidazole-4-one Nitration of the -N-phenyl (anilo) group at the C-4 position bridge-intact product Can form RPA-412708 by cleavage of the -N-N- bond
Aerobic soil metabolism and aerobic water-sediment system
studies ASM: 11.7%
RPA-413255 (RPA-410914) (5 S )-3,5-5-methyl-2-(methylthio)-3-[(2- nitrophenyl)amino]-5-phenyl-4 H

imidazole-4-one Nitration of the -N-phenyl (anilo) group at the C-2 position bridge-intact product. Can form RPA-412708 by cleavage of
the -N-N- bond
Aerobic soil metabolism and aerobic water-sediment system
studies ASM: 12.2%
RPA-409466 (RPA-4010995) 5-Methyl-3-[(4-nitrophenyl)amino-5— 2,4-imidazolidinedione (The code for the S -enantiomer is RPA221607) Nitration of the -N-phenyl (anilo) group at C-2 position bridgeintact product; Elimination of the methylthio group. Can form RPA-412636 by cleavage of the -N-N- bond Aerobic soil metabolism study
ASM: 12.6%
RPA-410995 (RPA-221701) 5-Methyl-3-[(2-nitrophenyl)amino-5— 2,4-imidazolidinedione (The code for the S -enantiomer is RPA221701) Nitration of the -N-phenyl (anilo) group at C-2 position bridgeintact product; Elimination of the methylthio group. Can form RPA-412636 by cleavage of the -N-N- bond Aerobic soil metabolism study ASM: 11.5%

a MRID 45723301

### 13 3. RECEPTORS

Tables 8 and 9 provide a summary of the aquatic and terrestrial taxonomic groups, respectively, and the most sensitive surrogate species tested to characterize the potential acute and chronic ecological effects of fenamidone. The tables prov ide a preliminary overvie w of the potential acute toxicity of fenamidone by providing the acute toxicity classifications. Based on the available ecotoxicity information, the organisms facing the grea test hazard are aquatic i nvertebrates and fish.

Table 8. Summary of the Most Sensitive En dpoints from Aquatic Toxicity Studies for
Fenamidone

Taxonomic

Group Study Type Surrogate Species
and Test Material Toxicity Value (all units in terms of

measured active ingredient) MRID and Classification Acute Toxicity Classification

Freshwater fish a Acute Rainbow trout Oncorhynchus mykiss LC 50 = 0.74 mg/L NOAEC = 0.35 mg/L based on lethality MRID 45385729 (Acceptable) Highly toxic

Chronic (Full life cycle) Fathead minnow Pimephales promelas NOAEC 0.0047 mg/L LOAEC = 0.010 mg/L
based on reductions in male body weight. MRID 48389201 (Acceptable) --

Estuarine/Marine
fish Acute Sheepshead
minnow Cyprinodon variegates LC 50 = 2.5 mg/L NOAEC = 1.1 mg/L based on lethality MRID 45385719 (Acceptable) Moderately
toxic

Chronic ACR not calculated due to a lack of data
--

Freshwater
invertebrates Acute Water flea Daphnia magna EC 50 = 0.049 mg/L NOAEC = 0.013 mg/L based on lethality MRID 45564601 (Acceptable) Very highly
toxic

Chronic Water flea Daphnia magna NOAEC = 0.0125 mg/L LOAEC = 0.029 mg/L based on growth and reproduction MRID 45385803 (Acceptable) --

Estuarine/Marine
invertebrates Acute Saltwater mysid Mysidiopsis bahia LC 50 = 0.069 mg/L NOEC = 0.047 mg/L MRID 45385721 (Acceptable) Very highly
toxic

Chronic Saltwater mysid Mysidiopsis bahia NOAEC = 0.0095 mg/L LOAEC = 0.019 mg/L based on growth and reproduction MRID 45385723 (Acceptable) --

Benthic
invertebrates Acute Midge
Chironomus tentans EC 50 = 4.5 mg/L NOAEC = 0.92 mg/L MRID 46797301 (Acceptable) Moderately
toxic

Chronic Midge
Chironomus tentans NOAEC = 1.14 mg/L (estimated) ACR b

--

### 14 Taxonomic

Group Study Type Surrogate Species
and Test Material Toxicity Value (all units in terms of

measured active ingredient) MRID and Classification Acute Toxicity Classification

Aquatic plants and algae Nonvascular Marine diatom
Skeletonema

costatum EC 50 = 0.07 mg/L NOAEC = 0.012 mg/L
based on reductions in cell density MRID 45385810 (Acceptable) --

Vascular Duckweed ( Lemna gibba )

TGAI EC 50 >0.88 mg/L NOAEC = 0.88 mg/L
based on reductions in frond density MRID 45385815 (Acceptable) --

a. Freshwater fish represent surrogates for aquatic-phase amphibian
b. Estimated using the acute-to-chronic ratio (A CR) for freshwater invertebrates (daphnids)



### Table 9. Summary of the Most Sensitive Endp oints from Terrestrial Toxicity Studies for
Fenamidone

Taxonomic

Group Study Type Surrogate Species Toxicity Values (all units in terms of measured a.i.) MRID and Classification Acute ToxicityClassification

Mammals Acute Oral Laboratory rat ( Rattus norvegicus ) LD 50 = 2028 mg/kg (F)
LD 50 >5000 mg/kg (M) MRID 45386011 (Acceptable) Practically
non-toxic

Chronic Laboratory rat ( Rattus norvegicus ) NOAEL= 1000 mg/kg diet LOAEL=5000 mg/kg diet Based on decreased body weight, body weight gains, and feed consumption d MRID
45400014 (Acceptable) --

Birds a Acute Oral Bobwhite quail (Colinus virginianus) LD 50 >2000 mg/kg bw NOAEL = 2000 mg/kg bw
No mortalities or sublethal effects reported MRID 45385804 (Acceptable) Practically
non-toxic

Subacute Dietary Bobwhite quail (Colinus virginianus) LC 50 >5040 mg/kg diet NOAEL = 5040 mg/kg diet
No treatment related
mortalities or sublethal effects reported MRID 45385805 (Acceptable) Practically
non-toxic

Chronic Mallard (Anas platyrhynchos) NOAEC =1016 mg/kg diet

e LOAEC >1016 mg/kg diet MRID
45385808 (Supplemental) ‐‐

Terrestrial

Insects Acute
Contact Honey Bee (Apis mellifera) LD 50 = 47.1 μg/bee NOAEC = 12.5 μg/bee based on lethargy and/or
uncoordinated movements MRID 45802901 Acceptable (contact)/ Supplemental Practically
non-toxic

### 15 Taxonomic

Group Study Type Surrogate Species Toxicity Values (all units in terms of measured a.i.) MRID and Classification Acute ToxicityClassification

Acute Oral Honey Bee (Apis mellifera) LD 50 = 159.8 μg/bee NOAEC = 79.2 μg/bee based on lethargy and/or
uncoordinated movements (oral)

Terrestrial

Plants Vegetative Vigor Dicot

No data
-- Monocot

Seedling Emergence Dicot-Lettuce EC 25 >1.07 lb/A
NOAEC = 1.07 lb/A based on shoot length and dry weight MRID
45386816 (Acceptable) --

Monocot EC 25 >1.07 lb/A
NOAEC = 1.07 lb/A
No effects to monocots.

a. Birds represent surrogates for terrestrial-phase amphibians and reptiles.
b. Based on acute contact LD 50 ( μ g a.i./bee) <2 highly toxic; 2-10.99 moderately toxic; ≥ 11 practically nontoxic

c. Acute Oral (avian/mammal): Based on LD 50 (mg/kg) <10 very highly toxic; 10-50 highly toxic; 51-500 moderately toxic; 501-2000 slightly toxic; >2000 practically nontoxic
d. Previously only considered reproductive endpoints, thus, NOAEL was 5000 ppm, however, reductions in weight gain are considered apical endpoints in EFED.

e. In a previously conducted one-generation reproduction study, fenamidone significantly reduced survivor weight at the highest dose tested (1614 ppm) and fema le weight gain at all treatment levels, therefore, a NOAEC could not be established (NOAEC=<395 ppm; MRID 45385808). However, when the study was repeated (MRID 46418601), there were no effects at any level up to 1016 ppm fenamidone. Chronic risk to birds will be estimated using the NOAEC of 1016 ppm. However, an analysis based on both of the values will be discussed in the Risk Description section.



### Toxicity data are available for several of the transformation products. The data are presented in Appendix E and are also discussed in more detail later in this document (see Stressors of Concern).

Exposure Pathways of Concern

The exposure pathways for fenamidone and its tr ansformation products may result in a wide range of potential aquatic and terrestrial exposure scenarios. For this problem formulation, the drinking water and inhalation pathways for birds and ma mmals were screened using the SIP (Screening Imbibition Program) and STIR (Screening Tool for Inhalation Risk) screening methods and were found to be exposure pathways of low concern. Howeve r, it is noted that the screening analysis do not include aggregation with all other exposure pathways (dietar y, dermal, inhalation, or drinking water), which, together, may contribute to a total exposure that has a potential for effects to nontarget animals. The risk characterization section will discusses the impact of the consideration of other routes of exposure that have been identi fied as potentially impor tant, and the degree of certainty associated with screening-level risk assessment conclusions. SIP and STIR are described in detail at http://www.epa.gov/oppefed1/models/te rrestrial/index.htm and the SIP and STIR model outputs are available in APPENDIX C and D , respectively.

### 16 4. ANALYSIS PLAN

Drinking Water Assessment

If needed, an updated drinking water assessment will be conducted to support future human health dietary risk assessments of fenamidone. The drinking water assessment will incorporate model estimates of fenamidone (as TTR) and any additiona l transformation products to those previously identified by the Health Effects Division as residu es of toxicological con cern in surface water and groundwater. The registration review drinking wate r assessment will include modeling results as well a summary of available surface water and groundwater monitoring data, if available.

The current models available for conducting dr inking water assessment fo r surface water include PRZM (Pesticide Root Zone Model, version 3.12.3, June 2006) and EXAMS (EXposure Analysis Modeling System, version 2.98.04.06, April 2005) models. PRZM will be used to simulate pesticide transport as a result of runoff and erosion from an agricultural field while EXAMS will be used to estimate environmental fate and transpor t of pesticides in the in dex reservoir. Measures of exposure will be based on maximum single an d year (including multiple seasons per year) labeled application rates, minimum retreatment intervals, and conservative methods of application.

Currently, groundwater modeling is completed using SCI-GROW (Screening Concentration in Groundwater, version 2.3, August 8, 2003) and PRZM-Groundwater (PRZM-GW version 1.0, December 11, 2012), using the GW-GUI (Graphical User Interface, version 1.0, December 11, 2012). SCI-GROW is an empirical model based on a linear best fit throu gh 13 single-application groundwater studies. PRZM-GW can be used to simu late vertical pesticid e transport through the soil profile into an aquifer followi ng application to an agricultural field. The PRZM scenarios used in groundwater simulations are representative of vulnerable sites—shallow unconfined aquifers under an agricultural field with leaching prone soil—and output values represent pesticide concentrations that may be observed in drinki ng water resulting from the use of groundwater vulnerable to pesticide contamination as source wa ter. The results are exp ected to represent the upper bound values on the concentrat ions of toxic residues that mi ght be found in drinking water supplied by groundwater.

Ecological Risk Assessment

Stressors of Concern

There are six major envir onmental transformation produc ts (RPA-412636, RPA-412708, RPA411639, RPA-413255, RPA-409446, RPA- 410995) and toxicity data are available for three of the major transformation products (RPA-412636, RP A-412708, RPA-413255) and one minor product, RPA-410193 ( Appendix E ).

Based on a review of the data for freshwater invertebrates ( Daphnia magna- acute exposure), the degradate toxicity is generally lower than that of the parent by at least tw o orders of magnitude.
Data are also available for two of the degradates (RPA-412636 and RPA-412708) for a nonvascular plant, [freshwater green algae ( Scenedesmus subspicatus )] and while the degradates

### 17 exhibited lower toxicity than the parent, a direct comparison is not possible because the parent toxicity test was conduc ted on a marine algae ( Skeletonema costatum). For acute exposure to freshwater fish, the LD 50 

### values were higher than the pare nt; however, the magnitude of the difference is not certain because of the non-definitive endpoints ( e.g., fenamidone LD 50 

### = 0.74 mg/L vs. RPA-412636 LD 50 

### >17.2 mg/L, RPA-412708 LD 50 

### >98 mg/L, and RPA-413255 LD 50 

### = >2.0 mg/L). Overall, the available aquatic toxici ty data for the transformation products supports the hypothesis that the degradates exhibit less toxicity than the parent. Toxicity data are not available for degradates RPA 411639, RPA-409446, and RPA-410995, however, these degradates only formed up to between 11.5-12.6% in the envir onmental fate studies. Additionally, visual comparisons of the structures shows that these three degradates are similar in structure to degradate RPA-413255, which according to the available data, is less toxic than the parent. While the toxicity of degradates RPA 411639, RP A-409446, and RPA-410995 is uncertain, given the overall toxicity profile of parent and degradates, there is no basis to consider these degradates to be stressors of concern for aquatic species.

Therefore, after reviewing the parent and degrad ate toxicity and exposur e profiles, the aquatic exposure values ( i.e., the EECs), for the registration review assessment will be based on exposure to fenamidone (parent) alone. Tables 10 and 11 provide a summary of the toxicity and
environmental fate data used to determine the stressors of concern fo r aquatic organisms.

Table 10. Summary of Aquatic Toxicity Data available for the Transformation Products

Taxa Chemical Toxicity: LC 50 

### (mg/L)

Acute: Freshwater fish (rainbow trout) Parent 0.74

RPA-412636 >17.2

RPA-412708 >98

RPA-413255 >2.0

Acute: Freshwater
invertebrates (water flea) Parent 0.049

RPA-412636 >97.2

RPA-412708 >100.8

RPA-413255 9.7
Aquatic non-vascular plants [Marine algae (parent)/freshwater green algae (degradates)] Parent 0.07

RPA-412636 17.3

RPA-412708 >18.7

### 18 Table 11. Summary of the Percent Formatio n of the Transformation Products

Degradate Percent of Total Applied Radioactivity in Respective Environmental Fate Studies (Maximum in bold)

RPA-412636 aerobic soil metabolism: 35% aerobic aquatic metabolism: 7.8%

RPA-412708 aquatic photolysis: 35.6% soil photolysis: 16.8-19.5%

aerobic soil metabolism:17.3% aerobic aquatic metabolism: 23.8

RPA-413255 aerobic soil metabolism: 12.2%

RPA 411639 aerobic soil metabolism: 11.7%

RPA-409446 aerobic soil metabolism: 12.6%

RPA-410995 aerobic soil metabolism: 11.5%



### For terrestrial animals, acute toxicity data are available for mammals for degradates RPA-412636 and RPA-412708. For RPA-412636, a definitive acute toxicity threshold was not determined ( e.g. the highest dose tested, 1520 mg a.i./kg bw, did not cause mortality in 50% of the individuals); however, considering the LD 50 

### is >1520 mg/kg-bw, this degradate is not considered a stressor of concern. In contrast, degr adate RPA-412708 was more acutely toxic to mammals (LD 50 

### =176 mg/kg-bw) than RPA-412636 and the parent, fenami done. Despite this higher toxicity, this degradate is not likely to be presen t in the environment at the same levels as the parent and in an analysis using EECs adjusted to 35% (conservatively using the hi ghest percent formation in the environmental fate studies), the resulting RQ values (based on the LD 50 

### of 176 mg a.i./kg-bw) were low (ranging from <0.01-0.15). Given the low RQ values and the conservatism in this approach, the risk to mammals from exposure to degradate RPA-412708 is considered to be similar to that of the parent ( i.e., low). The registration review assessment will be based on exposure to fenamidone alone; however, additiona l discussion of degradate, RPA-412708 will be included in the analysis.

Measures of Exposure

In order to estimate risks of fenamidone exposure to aquatic and terres trial organisms, all exposure modeling and resulting risk conclusions will be made based on maximum application rates, application methods, and any mitigation measures specifically indicated on the label. The models that will be used to predict the estimated environmental con centrations (EECs) of fenamindone are discussed on OPP’s model website. 9 

### These models include: PRZM and EXAMS, AgDrift, AgDisp, T-REX, TerrPlant, SIP (Screening Imbibition Program), and STIR (Screening Tool for Inhalation Risk).

9 http://www.epa.gov/opp00001/science/models_pg.htm

### 19 

## Measure of Effects

Ecological effects data are used as measures of di rect and indirect effect s to biological receptors. Data are typically obtained from registrant-submitte d studies or from literature studies identified by ECOTOX. The ECOTOX database provides more ecological effects data in an attempt to bridge existing data gaps. ECOTOX is a source fo r locating single chemical toxicity data and potential chemical mixture toxicity data for aqua tic life, terrestrial plants, and wildlife. ECOTOX was created and is maintained by the U.S. EPA, Office of Research a nd Development, and the
National Health and Environmental Effects Research Laboratory's Mid-Continent Ecology
Division.



## Integration of Exposure and Effects

Risk characterization is the integration of e xposure and ecological effects to determine the potential ecological risk from the use of pesticides and the likelihood of direct and indirect effects to non-target organisms in aquatic and terrestrial habitats. For the assessmen t of risks, the risk quotient (RQ) method is used to compare expos ure and measured toxicity values. EECs are divided by acute and chronic toxicity values. The resulting RQs are then compared to the Agency’s Levels of Concern (LOCs) (USEPA 2004) . These criteria will be used to indicate when fenamidone use, as directed on the label, has the poten tial to cause adverse dire ct or indirect effects to non-target organisms. In addition, any incident data from the EIIS, IDS, and AIMS will be considered as part of the risk characterization.



## Endangered Species Assessments

Consistent with the Agency’s responsibility under the Endangered Species Act (ESA), the Agency will evaluate exposure and potential risks to federally-listed threaten ed and/or endangered (listed) species from registered uses of pe sticides in registration review.



## Endocrine Disruptor Screening Program

Fenamidone is not included in the first group of 67 chemicals issued an order to conduct Tier 1 EDSP testing. For additional information on th e EDSP program, visit ht tp://www.epa.gov/endo/.

Review of Incident Data

A review of the Ecological Incident Informa tion System (EIIS, version 2.1) on November 6, 2013,
indicated an adverse field e ffect to non-target plants ( Table 12 ).

### 20 Table 12 . Incident Summary

PC Code Incident
ID Use Site Start
Date County Year Magnitude Appl.
Rate Appl.
Meth. Product

046679 I022286- 052 Spinach 4/28 Monterey,
CA 2010 100% of
2.9 acres 5.5 oz/A (product) Aerial Reason
500 SC (264-695) Legality: Undetermined; Certainty: Possible



### A review of the Avian Monitoring Information Sy stem (AIMS-maintained by the American Bird Conservancy), on November 6, 2013 did not identify any ecological incidents associated with the
use of fenamidone. In addition to the incidents r ecorded in EIIS and AIMS, the Agency maintains a database which stores counts of incidents that pe sticide registrants record in quarterly aggregated incident reports. A review of the aggregat e incident database on November 6, 2013, did not identify any minor fish, wildlife, plant, or ot her non-target incident a ssociated with use of
fenamidone.

Uncertainties

 Fenamidone has partial systemic activity with some movement in the plant and as a QoI fungicide, may also have translaminar movement through the plant surface layers 10 

### . A vegetative vigor study is not avai lable at this time but is n eeded to fully understand the risks to plants, especially given the systemic nature of fenamidone. Additionally, there was an incident reported for plant damage to 100% of a 2.9 acre field of spinach (see above).

 Another uncertainty related to the systemic na ture of fenamidone is that the T-REX model does not adjust for the amount of a.i. that coul d move into the plant (rather than dissipate over time), so the default foliar half-life of 35 days may not be conservative.

 The available acute freshwater fish toxicity studies were conducted using the rainbow trout and the bluegill and the chronic exposure was tested using the fathead minnow; thus, there is not a corresponding acute test to pair with the chronic test as is required by EPA’s pesticide data requirements for ecological eff ects (40 CFR 158.630). Without an acute test on the same species as used in the chronic te st, an acute to chroni c ratio (ACR) cannot be used to estimate the chronic toxicity to the most sensitive freshwater species. An acute toxicity test (96 hr) for fenamidone using th e fathead minnow would reduce the uncertainty for chronic exposures by providing a toxicity va lue to use for ACR estimates for the most
sensitive freshwater fish and the same ACR coul d also be used to estimate the chronic risk
to estuarine/marine fish.

10 U.S EPA. 2013. BEAD Chemical Profile for Regist ration Review: Fenamidone (1 29100).September 18, 2013

### 21 5. PRELIMINARY IDENTIFICATIO N OF DATA GAPS

Environmental Fate

Table 13 indentifies the environmental fate studies by MRID that offer data for each guideline requirement, as well as study classi fications and whether or not furt her data are anticipated to be required in order to support risk assessment for the fenamidone registration review.

Table 13. Submitted Environmenta l Fate Data for Fenamidone

OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Are data
needed to conduct risk assessment? Additional Comments

835.2120 Hydrolysis 4538 5929 Acceptable No -- 835.2240 Aqueous photolysis 45385830
45385831 Acceptable No Data available for

14 C-Phenyl fenamidone

14 C-N-Phenyl fenamidone 835.2410 Soil photolysis 45385832 Acceptable No Data available for

14 C-Phenyl fenamidone

14 C-N-Phenyl fenamidone 45385901

835.4100 Aerobic soil
metabolism 45385819 Acceptable No None

835.4100 Aerobic soil
metabolism 45385820 Acceptable No Degradate RPA-412636

835.4200 Anaerobic soil
metabolism - No study No None

835.4300 Aerobic aquatic
metabolism 45365621
45365622 Acceptable No None

835.4400 Anaerobic aquatic
metabolism 45400003 Acceptable No Data available for

14 C-Phenyl fenamidone

835.1230
835.1240 Adsorption/ desorption and leaching 45385823 Acceptable No None

835.1230 Adsorption/ desorption 453858-24
453858-28
453858-25
453858-26
453858-27 Acceptable No RPA-412636
RPA-412708
RPA-411639
RPA-413255

835.1410 Volatility – laboratory No study No study No Not triggered based on low vapor pressure (2.6 x 10 -9 torr at 20°C)

835.6100 Terrestrial field dissipation 45385904
45385905 Acceptable Acceptable No None

835.6200 Aquatic field dissipation No data No Not triggered based on exposure aquatic toxicity profile.

850.1730 Fish
bioconcentration No data No Low K
ow indicates a low potential for
bioaccumulation.

### 22 OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Are data
needed to conduct risk
assessment? Additional Comments

850.6100 Analytical
method in soil 45385817
45385818 Acceptable No Analytical method (ECM) and Independent Laboratory Validation (ILV) Fenamidone and metabolites

850.6100 Analytical
method in Water No data Yes An analytical method (ECM and ILV) for water is anticipated to be required

.



### Ecological Effects

Tables 14 and 15 identify the ecological effects studies , as well as study classifications, and whether or not further data are anticipated to be required in order to support risk assessment for registration review. The rationale for the additional data requeste d is presented below the tables.

Table14. Submitted Aquatic Ecological Effects Data for Fenamidone

OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Are data
needed to
conduct

risk
assessment? Comments

850.1010 Freshwater
invertebrate acute toxicity 45564601 Acceptable
No None

45385724 Supplemental

850.1025
850.1035
850.1045
850.1055 Saltwater
invertebrate acute toxicity 45385721 Acceptable

No None

45385720 Acceptable

850.1075 Freshwater fish acute toxicity 45385729 Acceptable

Yes An acute toxicity test (96 hr) for fenamidone (TGAI) using the fathead minnow is needed to pair with the
available chronic test for the fathead minnow. Having acute and chronic tests available from the same species is required (see 40 CFR 158.630) and the
data can be used to ensure that the chronic toxicity value (which may be calculated using an acute to chronic ratio-ACR) is based on the most sensitive freshwater species (currently the rainbow trout). 45385802 Acceptable

850.1075 Saltwater fish acute toxicity 45385719 Acceptable No None

850.1300 Freshwater
invertebrate

life cycle 45385803 Acceptable No None

### 23 OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Are data
needed to
conduct

risk assessment? Comments

850.1350 Saltwater
invertebrates

life cycle 45385723 Acceptable No None

850.1735 Benthic
invertebrates (acute) 46797301 Acceptable No None

850.1740 Benthic
invertebrates

(chronic)
No data No Data are not needed because the
available acute and chronic freshwater
invertebrate data for the Daphnia

magna allows for estimation of the chronic toxicity for the benthic invertebrate using an acute to chronic ratio (ACR) approach.

850.1400 Freshwater fish early-life stage 45385722 Supplemental No None

850.1400 Saltwater fish early-life stage No data Yes* *Data would not be necessary if a 96- hour acute toxicity test for the freshwater fathead minnow (see above)
was submitted. The freshwater minnow acute toxicity data could be paired with the respective chronic values for the
freshwater fish to calculate an ACR that along with the available acute saltwater toxicity values could then be used to estimate the chronic toxicity for a
saltwater fish.
850.1500 Fish life cycl e 48389201 Acceptable No None
46418602 Supplemental
850.4400 Aquatic plant growth:
Tier II vascular plants 45385815 Acceptable No None

850.5400 Aquatic Plant
Growth: Tier II algae 45385810 Acceptable

No None
45385812 Acceptable
45385811 Acceptable
45385809 Acceptable

### 24 Table 15. Submitted Terrestrial Ecologi cal Effects Data for Fenamidone

OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Are data needed for risk assessment? Comments

850.2100 Avian oral toxicity 45385804 Acceptable

No The low toxicity exhibited in all of the avian toxicity tests along with the low use rates suggests that risk to a passerine species is unlikely to exceed the levels of concern; therefore, passerine data are not anticipated to be required at this
time. No data for passerine

850.2200 Avian dietary toxicity 45385805 Acceptable No None
45385806 Acceptable

850.2300 Avian reproduction 46418601 Supplemental

No None
45385808 Supplemental

45385807 Acceptable

Nonguideline Avian inhalation No data No None

81-1 Acute mammalian
oral LD 50 (rat) 45386011 Acceptable No None

83-4 Mammalian Reproduction (rat) 45400014 Acceptable No None

850.3020 Honey bee acute contact toxicity 45802901 Acceptable No None

Nonguideline Honey bee acute oral toxicity 45802901 Acceptable No None

850.3030 Honey bee residue on foliage No data No None

850.3040 Field testing for pollinators No data No None

850.4100 Terrestrial plant toxicity: Tier II seedling

emergence 45386816 Acceptable No None

### 25 OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Are data needed for risk assessment? Comments

850.4150 Terrestrial plant toxicity: Tier II vegetative vigor No data Yes Given that fenamidone has systemic activity and may have translaminar movement through the plants surface, a vegetative vigor study is anticipated to be required to fully understand the risk to plants. Additionally, there was an incident reported for plant damage to spinach.

124-1 Terrestrial Plant Field Testing No data No None

124-2 Aquatic Plant Field Testing No data No None



### Table 16. Submitted Terrestrial Ecologica l Effects Data for Degradate RPA-412636

OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Are data needed to conduct risk
assessment? Comments

81-1 Mammal LD 50 (rat) 45386113 Acceptable No None

850.1010 Freshwater
invertebrate acute toxicity 45385725 Acceptable No None

850.1075 Freshwater fish acute toxicity 45385730 Supplemental No None

850.5400 Aquatic Plant
Growth: Tier II algae 45385813 Supplemental No None



### Table 17. Submitted Terrestrial Ecologica l Effects Data for Degradate RPA-412708

OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Are data needed to conduct risk assessment? Comments

81-1 Mammal LD 50 (rat) 45386123 Acceptable No None

850.1010 Freshwater
invertebrate acute toxicity 45385727 Acceptable No None

850.1075 Freshwater fish acute toxicity 453857301 Acceptable No None

850.5400 Aquatic Plant
Growth: Tier II algae 45385814 Supplemental No None

### 26 Table 18. Submitted Terrestrial Ecologica l Effects Data for Degradate RPA-413255

OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Are data needed to conduct risk
assessment? Comments

850.1010 Freshwater
invertebrate acute toxicity 45385728 Acceptable No None

850.1075 Freshwater fish acute toxicity 45385801 Supplemental No None



### Table 19. Submitted Terrestrial Ecologica l Effects Data for Degradate RPA-410193

OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Are data needed to conduct risk assessment? Comments

850.1010 Freshwater
invertebrate acute toxicity 45385726 Supplemental No None

### 27 Appendix A Proposed De gradation Pathways

Appendix A Figure 1. Proposed Metabol ic Pathway of Fenamidone in Soil

### 28 Appendix A Figure 2. Proposed Pathway for th e Photodegradation of Fenamidone in a Solution Buffered at pH 7.0

### 29 Appendix A Figure 3. Proposed Pathway for the Hydrolysis of Fenamidone.

### 30 APPENDIX B

Appendix B. Chemical Struct ures of Fenamidone and Major Transformation Products

Fenamidone (Reason ® 

### 500 SC)
RPA-407213 (5 S )-3,5-dihydro-5-methyl-2-methio-5-phenyl -3-(phenylamino)-4H- imidazolin-4-one
CAS No. 161326-34-7
S -enantiomer of racemic mixture of RPA-405803

RPA-412636 (S)-Methyl-5-phenylimidazolidine-2,4-dione
CAS No. 27539-12-4
S -enantiomer of racemic mixture of RPA-717879

RPA-412708 (5 S )-3,5-dihydro-5-methyl-2-(methylthio)- 5-phenyl-4H-imidazole-4-one (CA)
CAS No. 33285-82-0
S -enantiomer of racemic mixture of RPA-408056

### 31 RPA-413255 (5 S )-3,5-dihydro-5-methyl-2-(methylthio)-3-[(2-n itrophenyl)amino]-5-phenyl-4H-imidazole-4-one
S -enantiomer of racemic mixture of RPA-410914

RPA-413639 (5 S )-3,5-dihydro-5-methyl-2-(methylthio)-3-[(4-n itrophenyl)amino]-5-phenyl-4H-imidazole-4-one
S -enantiomer of racemic mixture of RPA-406012

RPA-411093 (5 S )-5-methyl-5-phenyl-3-(phenylamino)-2,4-imi dazolelidinedione
CAS No. 332855-88-6
S -enantiomer of racemic mixture of RPA-405862

### 32 RPA-418915 ( S )-5-Methyl-2-methylthio-3-[ 4-oxo-2,5-cyclohexadien-1-ylidene)amino ]-5-phenyl-3,5-dihydroimidazol-4-one

RPA-221607 (5 S )-5-methyl-3-[(4-n itrophenyl)amino]-5-phenyl- 2,4-imidazolidinedione
S -enantiomer of racemic mixture of RPA-409446

RPA-221701 (5 S )-5-methyl-3-[(2-n itrophenyl)amino]-5-phenyl- 2,4-imidazolidinedione
S -enantiomer of racemic mixture of RPA- 410995

### 33 RPA-409344 (R, S )-2-methyl-2-phenyl-N-( phenylazocarbonyl)glycine R, S )-2-phenyl-2-(phenylazocarbony lamino)propionic acid

### 34 APPENDIX C

SIP ANALYSIS

Parameter Value

Chemical name Fenamidone

Solubility (in water at 25 o C; mg/L) 7.8

Mammalian LD 50 (mg/kg-bw) 2028
Mammalian test species laboratory rat
Body weight (g) of "other" mammalian species

Mammalian NOAEL (mg/kg-bw) 50
Mammalian test species laboratory rat
Body weight (g) of "other" mammalian species

Avian LD 50 (mg/kg-bw) 2000
Avian test species northern bobwhite quail
Body weight (g) of "other" avian species
Mineau scaling factor 1.15

Mallard NOAEC (mg/kg-diet) 1016
Bobwhite quail NOAEC (mg/kg-diet) 1640
NOAEC (mg/kg-diet) for other bird species
Body weight (g) of other avian species
NOAEC (mg/kg-diet) for 2nd other bird species
Body weight (g) of 2nd other avian species

Table 2. Mammalian Results

Parameter Acute Chronic
Upper bound exposure (mg/kg-bw) 1.3416 1.3416
Adjusted toxicity value (mg/kg-bw) 1559.8576 38.4580
Ratio of exposure to toxicity 0.0009 0.0349

Conclusion* Drinking water exposure alone is NOT a potential concern for mammals Drinking water exposure alone is NOT a potential concern for mammals

Table 3. Avian Results

Parameter Acute Chronic
Upper bound exposure (mg/kg-bw) 6.3180 6.3180
Adjusted toxicity value (mg/kg-bw) 1440.8590 50.4064
Ratio of exposure to acute toxicity 0.0044 0.1253

Conclusion* Drinking water exposure alone is NOT a potential concern for birds Drinking water exposure alone is NOT a potential concern for birds

*Conclusion is for drinking water exposure alone. This does not combine all routes of exposure. Therefore, when aggregated with other routes ( i.e ., diet, inhalation, dermal), pesticide exposure through drinking water may contribute to a total exposure that has potential for effects to non-target animals.

### 35 APPENDIX D STIR Analysis Results

Application and Chemical Information

Enter Chemical Name Fenamidone

Enter Chemical Use Potatoes
Is the Application a Spray? (enter y or n) y If Spray What Type (enter ground or air) ground
Enter Chemical Molecular Weight (g/mole) 311.4
Enter Chemical Vapor Pressure (mmHg) 2.60E-09
Enter Application Rate (lb a.i./acre) 0.267

Toxicity Properties

Bird

Enter Lowest Bird Oral LD 50 (mg/kg bw) 2000
Enter Mineau Scaling Factor 1.15
Enter Tested Bird Weight (kg) 0.178

Mammal

Enter Lowest Rat Oral LD 50 (mg/kg bw) 2028

Enter Lowest Rat Inhalation LC 50 (mg/L) 2.1
Duration of Rat Inhalation Study (hrs) 4
Enter Rat Weight (kg) 0.35

Output

Results Avian (0.020 kg )

Maximum Vapor Concentration in Air at Saturation (mg/m 3 ) 4.36E-05
Maximum 1-hour Vapor Inhalation Dose (mg/kg) 5.48E-06

Adjusted Inhalation LD 50 1.15E+01

Ratio of Vapor Dose to Adjusted Inhalation LD 50 4.74E-07 Exposure not Likely Significant
Maximum Post-treatment Spray Inhalation Dose (mg/kg) 2.82E-02

Ratio of Droplet Inhalation Dose to Adjusted Inhalation LD 50 2.44E-03 Exposure not Likely Significant

Results Mammalian (0.015 kg )

Maximum Vapor Concentration in Air at Saturation (mg/m 3 ) 4.36E-05
Maximum 1-hour Vapor Inhalation Dose (mg/kg) 6.88E-06

Adjusted Inhalation LD 50 1.25E+02

Ratio of Vapor Dose to Adjusted Inhalation LD 50 5.51E-08 Exposure not Likely Significant
Maximum Post-treatment Spray Inhalation Dose (mg/kg) 3.55E-02

Ratio of Droplet Inhalation Dose to Adjusted Inhalation LD 50 2.84E-04 Exposure not Likely Significant

### 36 

## Appendix E. Degradate Toxicity Data

Appendix E Table 1. Toxicity Studies for degradate RPA-412636

Taxonomic

Group Study Type Surrogate Species
and Test Material Toxicity Value MRID and Classification Acute Toxicity Classification

Mammals Acute Rat Rattus norvegicus LD 50 >1520 mg/kg bw 45386113 (Acceptable) No more than slightly toxic

Freshwater fish Acute Rainbow trout Oncorhynchus mykiss LC 50 >17.2 mg/L NOAEC = 17.2 mg/L 45385730 (Supplemental) No more than slightly toxic

Freshwater
invertebrates Acute Water flea Daphnia magna EC 50 >97.4 mg/L NOAEC = 97.4 mg/L 45385725 (Acceptable) No more than slightly toxic

Freshwater plants Acute Freshwater algae
Scenesdesmus

subspicatus EC 50 17.3mg/L NOAEC =>33.5 mg/L 45385814 (Supplemental) --



### Appendix E Table 2. Toxicity Studies for degradate RPA-412708

Taxonomic

Group Study Type Surrogate Species

and Test Material Toxicity Value MRID and Classification Acute Toxicity Classification

Mammals Acute
oral Laboratory Rat LD50= 176 mg/kg-bw 45386123 (Acceptable) Moderately
toxic

Freshwater fish Acute Rainbow trout Oncorhynchus mykiss LC 50 >98 mg/L 453857301 (Acceptable) No more than slightly toxic

Freshwater
invertebrates Acute Water flea Daphnia magna EC 50 > 100.8 mg/L 45385727 (Acceptable) Practically
non-toxic

Freshwater plants Acute Freshwater algae
Scenesdesmus

subspicatus EC 50 >18.7mg/L NOAEC = 18.7mg/L 45385813 (Supplemental) --



### Appendix E Table 3. Toxicity Studies for degradate RPA-413255

Taxonomic

Group Study Type Surrogate Species
and Test Material Toxicity Value MRID and Classification Acute Toxicity Classification

Freshwater fish Acute Rainbow trout Oncorhynchus mykiss LC 50 >2.0 mg/L 45385801 (Supplemental) No more than moderately

toxic --
Freshwater
invertebrates Acute Water flea Daphnia magna EC 50 9.7mg/L 45385728 (Acceptable) Moderately
toxic

### 37 Appendix E Table 4. Toxicity Studies for degradate RPA-410193

Taxonomic Group Study Type Surrogate Species
and
Test Material Toxicity Value MRID and
Classification Acute Toxicity
Classification

Freshwater
invertebrates Acute Water flea Daphnia magna EC 50 >5.5 mg/L MRID 45385726 (Supplemental) No more than moderately
toxic