UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON D.C., 20460 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION 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 

Environmental 

Environmental 

Katherine R. Stebbins, 

Fate 

Risk 

and 

Branch 

Biologist 

Effects 

3 

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 

registration 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 spectrum fungicide for control of certain pathogenic 

fungal diseases in a variety of crops including potatoes and other tuberous and corm vegetables, 

tomatoes, onions and other bulb vegetables, root vegetables, grapes, turnip greens, okra, 

coriander, lettuce, leafy vegetables, brassica vegetables, tobacco, fruiting vegetables, carrots, 

cucurbit crops, ornamentals, cotton and sunflower. 

Fenamidone belongs to the imidazole chemical family of fungicides, which includes iprodione 

and cyazofamid. Fenamidone is classified as a “Quinone outside Inhibitor” (QoI), which inhibits 

mitochondrial respiration by blocking electron transfer at the Complex III level in several plant 

pathogenic fungi species. 

The chemical structure of fenamidone and several chemical identifiers are provided in Table 1. 

Table 1. Fenamidone Chemical Identifiers 

Chemical Name (+)-(4S)-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 broadcast treatment via ground, chemigation or aerial 

equipment for a variety of terrestrial agricultural crops. Additionally, fenamidone may be applied 

as a soil in-furrow application for cotton, as a pre-plant soil incorporation application for 

tobacco, and also as a slurry or mist for seed treatments (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 pressurized 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 registered labels are on a per season basis. The 

number of applications of fenamidone that can be applied per calendar year on a given field is 

not explicitly stated on current labels. As such, several of the currently registered uses may result 

in multiple seasonal applications of fenamidone per year. 

Fenamidone was first registered in 2002. According to the Biological and Economic Analysis 

Division Report1

, agricultural use has steadily increased during the 2005-2011 time period (use 

was not reported from 2002-2004). On average, 23,000 pounds of fenamidone were applied 

annually to 106,000 acres, at an average application rate of 0.2 pounds of active ingredient per 

acre (lb. a.i./acre). The maximum single application 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 consistent with the regional use being 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. 
4 

Table 2. Registered Fenamidone Uses and Application Rates

Crop/Site 

Residential 

Agricultural 

Forestry (Timing) and Application Type Method/ Equipment 

Maximum 

Single 

Application 

Rate by 

Formulation

(lb a.i./A) 

Maximum 

Application Rate 

Maximum 

Application 

Number 

PHI (days)

REI (hours)

MRI (days)

Per Year 

lb a.i./A 

Per CC

lb a.i./A 

Per 

Yeari

Per 

CC

Brassica (Cole) leafy vegetables and turnip greens a



(Foliar) 

Aerial, 

Ground, 

Chemigation 

Aircraft, 

ground, 

irrigation 

0.264 NS 0.793 NS 3h 2 12 5 

Bulb vegetablesb 

(Foliar) 

Aerial, 

Ground, 

Chemigation 

Aircraft, 

ground, 

irrigation 0.177 NS 0.709 NS 4h 7 12 5 

Carrot 



(Foliar) 

Ground, 

Chemigation 

Directed 

spray, 

irrigation 

0.264 NS 0.793 NS 3h 14 12 14 

Cotton 



At planting 

(soil in furrow) Ground 0.00001452 lb / linear ft NS 0.264 NS NS NS 12 NS 

Seed trt. Mist or slurry seed treater 0.00050002 lb / lb of seed NS NS NS NS NS NS NS 

Cucurbit c 

(Foliar) 

Aerial, 

Ground, 

Chemigation 

Aircraft, 

ground, 

irrigation 0.177 NS 0.709 NS 4h 14 12 5 

Grapes 



(Foliar) 

Aerial, 

Ground, 

Chemigation 

Aircraft, 

ground, 

irrigation 

0.0871 NS 0.261 NS 3h 30 12 10 

Leafy vegetables (except brassica)d



(Foliar) 

Aerial, 

Ground, 

Chemigation 

Aircraft, 

ground, 

irrigation 

0.264 NS 0.793 NS 3h 2 12 5 

2 Becker, Jonathan and Ratnayake, Sunil. Acres Planted per Day and Seeding rates of Crops Grown in the United States. 2011. Biological a

Division (BEAD) Office of Pesticide Programs. United States Protection Agency 
5

Crop/Site 

Residential 

Agricultural 

Forestry (Timing) and Application Type Method/ Equipment 

Maximum 

Single 

Application 

Rate by 

Formulation

(lb a.i./A) 

Maximum 

Application Rate 

Maximum 

Application 

Number 

PHI (days)

REI (hours)

MRI (days)

Per Year 

lb a.i./A 

Per CC

lb a.i./A 

Per 

Yeari

Per 

CC

Potatoes and other Tuberous and Corm e 



(Foliar) 

Aerial, 

Ground, 

Chemigation 

Aircraft, 

ground, 

irrigation 

0.264 NS 0.793 NS 3h 14 12 5 

Tomatoes, peppers and other fruiting vegetables (except cucurbits)f



(Foliar) 

Aerial, 

Ground, 

Chemigation 

Aircraft, 

ground, 

irrigation 

0.264 NS 0.793 NS 3h 14 12 5 

Root vegetables (except carrot, potato, radish and sugarbeet)g



(Foliar) 

Aerial, 

Ground, 

Chemigation 

Aircraft, 

ground, 

irrigation 

0.264 NS 0.793 NS 3h 14 12 14 

Sunflower 

 Seed trt. Mist or slurry seed treater 0.00187104 lb / lb of seed NS NS NS NS NS NS NS 

Tobacco 



(Pre-plant 

and Foliar) 

Aerial, 

Ground, 

Chemigation 

Soil inc., 

aircraft, 

ground, 

irrigation 

0.264 NS 0.793 NS 3h 30 12 5 

Ornamentals (Greenhouse and saran house use only) 



Drench 

Flood, Drip, 

Sprinkler 

49.17* NS NS NS 4 NS 12 NS 

(Foliar) 

Ground, 

Chemigation 

1.806 NS NS NS 2 NS 12 NS 

3 Becker, Jonathan and Ratnayake, Sunil. Acres Planted per Day and Seeding rates of Crops Grown in the United States. 2011. Biological a

Division (BEAD) Office of Pesticide Programs. United States Protection Agency 
6

Crop/Site 

Residential 

Agricultural 

Forestry (Timing) and Application Type Method/ Equipment 

Maximum 

Single 

Application 

Rate by 

Formulation

(lb a.i./A) 

Maximum 

Application Rate 

Maximum 

Application 

Number 

PHI (days)

REI (hours)

MRI (days)

Per Year 

lb a.i./A 

Per CC

lb a.i./A 

Per 

Yeari

Per 

CC

a Broccoli, Broccoli (Chinese, gai lon), Broccoli raab (rapini), Brussels sprouts, Cabbage, Cabbage Chinese (bok choy),Cabbage Chinese (Napa), Cabbage Chinese m

broccolo, Collards, Kale, Kohlrabi, Mizuna, Mustard greens, Mustard spinach, Rape greens), Turnip greens 

b Chive, fresh leaves; chive, Chinese, fresh leaves; daylily, bulb; elegans hosta; fritillaria, bulb; fritillaria, leaves; garlic, bulb; garlic, great-headed, bulb; garlic, serpe

lily, bulb; onion, Beltsville bunching; onion, bulb; onion, Chinese, bulb; onion, fresh; onion, green; onion, macrostem; onion, pearl; onion, potato, bulb; onion, tree, t

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 (summer and winter) and watermelon d Amaranth (leafy amaranth, Chinese spinach, tampala), Arugula (roquette), Cardoon, Celery, Chinese celery, Celtuce, Chervil, Chrysanthemum (edible-leaved), Chr

salad, Cress (garden), Cress (upland), Dandelion, Dock (sorrel), Endive (escarole), Fennel florence (finochio), Lettuce (head and leaf), Orach, Parsley, Purslane (gard

chicory), Rhubarb, Spinach, Spinach New Zealand, Spinach vine (Malabar spinach, Indian spinach), Swiss chard) 

e. Arracacha, arrowroot, artichoke (Chinese), artichoke (Jerusalem), canna (edible), cassava (bitter and sweet), chayote (root), 

chufa, dasheen, ginger, leren, potato, sweet potato, tanier, turmeric, yam (bean and true) 

f Eggplant, Groundcherry, Okra, Pepino, Pepper (bell, chili, cooking, pimento, sweet), Tomatillo, Tomato g. 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, Turnip 

h Maximum number of applications not specified on label. Value derived by dividing the maximumseasonal rate by the maximum application rate. i For all crops except Brassica and Leafy vegetables, the number of crop cycles per year is assumed to be one. For Brassica and Leafy vegetables, two to three crop 

on 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-lettuce, 10/2/02), (New Use-potatoes, tuberous and corm, lettuce, 

tomatoes, cucurbits, bulb vegetables and ornamentals, 7/16/04), (New Use-carrots, leafy 

vegetables, brassica, fruiting vegetables, and tobacco, 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 toxicity, exposure, and usage information to determine if sufficient 

data are available and if further updates are needed to support registration review. 

Based on previous assessments, there is the potential for risk to aquatic invertebrates from acute 

and chronic exposure and to fish from chronic exposure. The previous assessments 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 Concerns Identified for Fenamidone

Exposure 

Basis Birds Mammals 

Terrestrial 

Plants 

Terrestrial 

Inverts. 

(honey 

bee 

hazard) 

Fish Aquatic 

Inverts 

Aquatic 

Plants 

Groundwater 

Contamination 

Persistence Degradates 

of Concern 

Acute No No

No No 

No Yesa

Yesb Yesc

 Yesc Yesc

Chronic No No Yesa,d Yesa

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 conducted ecological risk assessments were based on modeling total 

fenamidone residues, which included six major transformation products4; however, based on the 

available toxicity data for some of the degradates, 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 season) per calendar year. The registration 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 calendar 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 residues was conducted in 2007 [Hetrick, Termes and 

Whitby, 20075

] to include the parent fenamidone and its transformation products using the total 

toxic residues (TTR) approach. Based upon the recommendation from the Metabolism Assessment 

Review Committee (MARC)6

, the following transformation products were included in the total 

toxic residues: RPA-412636, RPA-412708, RPA-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 annual mean concentration, respectively, and 5.99 

μg/L the 30-year annual mean concentrations. Based on SCI-GROW, the estimated total 

fenamidone residue concentration in groundwater would not be expected to exceed 178 μg/L. The 

previous drinking water assessment was also based upon one crop cycle (or season) per calendar 

year.

Clean Water Act Programs 

Fenamidone is not identified as a cause of impairment for any water bodies listed as impaired 

under section 303(d) of the Clean Water Act. Total Maximum Daily Load (TMDL) criteria have 

not been developed for fenamidone. Aquatic benchmarks have not been established for 

fenamidone (http://www.epa.gov/oppefed1/ecorisk_ders/aquatic_life_benchmark.htm). Any data 

submitted or otherwise located as part of the registration review process may be used to establish 

aquatic life benchmarks, if applicable. 

2. ENVIRONMENTAL FATE AND TRANSPORT 

Physical and Chemical Properties of Fenamidone 

A major chemical feature of fenamidone is the presence 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 C17H17N3OS 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 m3

 mole-1 Calculated 

 

5

 Hetrick, J.A., S.C. Termes, and K. Whitby, 2007. Fenamidone. Drinking Water Assessment 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 KOW) 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, and 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/goc) and appears to degrade faster in aerobic 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 fenamidone over a period of 30 days (i.e., length of the study). 

Although direct photolysis occurred rapidly in laboratory studies (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 soil photodegradation study indicated no evidence of 

phototransformation on soil. The Koc and Kow indicate that fenamidone may partition to sediments. 

Partitioning to sediments was observed to increase with time in the aerobic aquatic metabolism 

study. The terminal degradation product RPA-412636 observed in the aerobic soil metabolism, 

aerobic aquatic metabolism studies (and the terrestrial field dissipation study) is more persistent 

(half-lives 105 to 462 days) and mobile (average Koc = 26 mL/goc). 

Table 5. Chemical Properties and Environmental 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 of 

degradate 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 (KF); organic carbonnormalized Freundlich coefficients 

(KFOC) 

mL/g; 

2.43, 5.93, 6.93, 8.90, 4.93 

mL/gOC; 

486, 494, 313, 387, 259 Avg. = 387.8 mL/goc

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 aerobic soils and water-sediment 

systems, and is persistent (aerobic soil half-lives as long as 462 days) (Table 5). The major 

degradate observed in the aerobic water-sediment systems was RPA-412636. In the aerobic soil 

metabolism studies the major transformation products were RPA-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 transformation product observed in the 

aqueous photolysis study was RPA-4127087

. The summary of degradation processes are found in 

Table 7, and the structures are shown in Appendix B. 

Batch equilibrium partition coefficients of several fenamidone transformation products are shown 

in Table 6. RPA-412636 (avg. Koc =26 mL/goc) and its immediate precursor RPA-412708 

(cleavage product; avg. Koc =31 mL/goc) are very mobile8

 in soil. RPA-411639 and RPA-413255 

are moderately mobile with average Kocs of 611 and 458 mL/goc, respectively. 

Table 6: Batch Equilibrium Coefficients for Four Fenamidone Degradation Products 

Degradate Code Sorption Coefficients KF/ Koc 

(mL/g; 

mL/goc) 

Data Source 

(MRID) 

RPA-412636b 0.11, 0.43, 0.64; 0.32; 0.56 

23, 36, 28, 17, 28 

45385824 

RPA-412708a 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. 

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

In terrestrial field dissipation 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) was detected down to 75 cm 0.006 mg/g). At 

the California site, RPA-717879 was detected at quantifiable 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 Classification 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), Chemical 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) 

(5S)-3,5-dihydro-5-methyl-2-

(methylthio)-5-phenyl-4H-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) 

 

(5S)-3,5-5-methyl-2-(methylthio)-3-[(4-

nitrophenyl)amino]-5-phenyl-4Himidazole-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) 

(5S)-3,5-5-methyl-2-(methylthio)-3-[(2-

nitrophenyl)amino]-5-phenyl-4Himidazole-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 provide a preliminary overview of the potential acute 

toxicity of fenamidone by providing the acute toxicity classifications. Based on the available 

ecotoxicity information, the organisms facing the greatest hazard are aquatic invertebrates and fish. 

Table 8. Summary of the Most Sensitive Endpoints 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 fisha

Acute 

Rainbow trout 

Oncorhynchus 

mykiss

LC50 = 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

LC50 = 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

EC50 = 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

LC50 = 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

EC50 = 4.5 mg/L 

NOAEC = 0.92 mg/L 

MRID 46797301 

(Acceptable) 

Moderately 

toxic 

Chronic Midge 

Chironomus tentans

NOAEC = 1.14 mg/L 

(estimated) ACRb

 -- 
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

EC50 = 0.07 mg/L 

NOAEC = 0.012 mg/L 

based on reductions in 

cell density 

MRID 45385810 

(Acceptable) -- 

Vascular 

Duckweed 

(Lemna gibba) 

TGAI 

EC50 >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 (ACR) for freshwater invertebrates (daphnids)

Table 9. Summary of the Most Sensitive Endpoints 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 

Toxicity 

Classification 

Mammals 

Acute Oral Laboratory rat 

(Rattus norvegicus) 

LD50 = 2028 mg/kg (F) 

 LD50 >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 consumptiond 

MRID 

45400014 

(Acceptable) 

-- 

Birdsa

Acute Oral Bobwhite quail 

(Colinus virginianus) 

LD50 >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) 

LC50 >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)

LD50 = 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 

Toxicity 

Classification 

Acute Oral Honey Bee 

(Apis mellifera)

LD50 = 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 

EC25 >1.07 lb/A 

NOAEC = 1.07 lb/A based 

on shoot length and dry 

weight 

MRID 

45386816 

(Acceptable) 

-- 

Monocot

EC25 >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 LD50 (μg a.i./bee) <2 highly toxic; 2-10.99 moderately toxic; ≥11 practically nontoxic 

c. Acute Oral (avian/mammal): Based on LD50 (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 female 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 transformation 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 mammals 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. However, it is noted that the screening analysis do 

not include aggregation with all other exposure pathways (dietary, 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 identified as potentially important, 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/terrestrial/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 additional transformation products to those previously 

identified by the Health Effects Division as residues of toxicological concern in surface water and 

groundwater. The registration review drinking water 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 drinking water assessment for 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 transport of pesticides in the index reservoir. Measures 

of exposure will be based on maximum single and 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 through 13 single-application 

groundwater studies. PRZM-GW can be used to simulate vertical pesticide transport through the 

soil profile into an aquifer following 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 drinking water resulting from the use of groundwater 

vulnerable to pesticide contamination as source water. The results are expected to represent the 

upper bound values on the concentrations of toxic residues that might be found in drinking water 

supplied by groundwater. 

Ecological Risk Assessment 

Stressors of Concern 

There are six major environmental transformation products (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, RPA-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 two 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 conducted on a marine algae (Skeletonema costatum). For acute exposure to 

freshwater fish, the LD50 values were higher than the parent; however, the magnitude of the 

difference is not certain because of the non-definitive endpoints (e.g., fenamidone LD50= 0.74 

mg/L vs. RPA-412636 LD50 >17.2 mg/L, RPA-412708 LD50 >98 mg/L, and RPA-413255 LD50 = 

>2.0 mg/L). Overall, the available aquatic toxicity 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 environmental 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, RPA-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 degradate toxicity and exposure 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 for aquatic organisms. 

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

Taxa Chemical 

Toxicity: LC50

(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 Formation 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 LD50 is >1520 mg/kg-bw, this degradate is not considered a stressor of 

concern. In contrast, degradate RPA-412708 was more acutely toxic to mammals (LD50=176 

mg/kg-bw) than RPA-412636 and the parent, fenamidone. Despite this higher toxicity, this 

degradate is not likely to be present in the environment at the same levels as the parent and in an 

analysis using EECs adjusted to 35% (conservatively using the highest percent formation in the 

environmental fate studies), the resulting RQ values (based on the LD50 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, additional 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 terrestrial 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 concentrations (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 direct and indirect effects to biological receptors. 

Data are typically obtained from registrant-submitted 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 for locating single chemical toxicity data and 

potential chemical mixture toxicity data for aquatic life, terrestrial plants, and wildlife. ECOTOX 

was created and is maintained by the U.S. EPA, Office of Research and 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 exposure 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 assessment of risks, the risk 

quotient (RQ) method is used to compare exposure 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 potential to cause adverse direct 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 threatened and/or endangered (listed) 

species from registered uses of pesticides 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 the EDSP program, visit http://www.epa.gov/endo/. 

Review of Incident Data 

A review of the Ecological Incident Information System (EIIS, version 2.1) on November 6, 2013, 

indicated an adverse field effect 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 System (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 recorded in EIIS and AIMS, the Agency maintains 

a database which stores counts of incidents that pesticide registrants record in quarterly aggregated 

incident reports. A review of the aggregate incident database on November 6, 2013, did not 

identify any minor fish, wildlife, plant, or other non-target incident associated 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 layers10. A 

vegetative vigor study is not available at this time but is needed 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 nature of fenamidone is that the T-REX model 

does not adjust for the amount of a.i. that could 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 effects (40 CFR 158.630). Without an acute test 

on the same species as used in the chronic test, an acute to chronic 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 the fathead minnow would reduce the uncertainty 

for chronic exposures by providing a toxicity value to use for ACR estimates for the most 

sensitive freshwater fish and the same ACR could also be used to estimate the chronic risk 

to estuarine/marine fish. 

 

10 U.S EPA. 2013. BEAD Chemical Profile for Registration Review: Fenamidone (129100).September 18, 2013 
21

5. PRELIMINARY IDENTIFICATION 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 classifications and whether or not further data are anticipated to be 

required in order to support risk assessment for the fenamidone registration review. 

Table 13. Submitted Environmental 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 45385929 Acceptable No -- 

835.2240 Aqueous 

photolysis 

45385830 

45385831 

Acceptable No Data available for 14C-Phenyl fenamidone 

14C-N-Phenyl fenamidone 

835.2410 Soil photolysis 45385832 Acceptable No Data available for 

14C-Phenyl fenamidone 

14C-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 

14C-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 Kow 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 requested 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 cycle 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 Ecological 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 LD50

(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 Ecological 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 LD50 (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 Ecological 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 LD50 (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 Ecological 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 Ecological 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 Degradation Pathways 

Appendix A Figure 1. Proposed Metabolic Pathway of Fenamidone in Soil 
28

Appendix A Figure 2. Proposed Pathway for the 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 Structures of Fenamidone and Major Transformation Products 

Fenamidone (Reason® 500 SC) 

RPA-407213 

(5S)-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 

(5S)-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 

(5S)-3,5-dihydro-5-methyl-2-(methylthio)-3-[(2-nitrophenyl)amino]-5-phenyl-4H-imidazole-4-one 

S-enantiomer of racemic mixture of RPA-410914 

RPA-413639 

(5S)-3,5-dihydro-5-methyl-2-(methylthio)-3-[(4-nitrophenyl)amino]-5-phenyl-4H-imidazole-4-one 

S-enantiomer of racemic mixture of RPA-406012 

RPA-411093 

(5S)-5-methyl-5-phenyl-3-(phenylamino)-2,4-imidazolelidinedione 

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 

(5S)-5-methyl-3-[(4-nitrophenyl)amino]-5-phenyl-2,4-imidazolidinedione 

S-enantiomer of racemic mixture of RPA-409446 

RPA-221701 

(5S)-5-methyl-3-[(2-nitrophenyl)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-(phenylazocarbonylamino)propionic acid 

 
34

APPENDIX C 

SIP ANALYSIS 

Parameter Value 

Chemical name Fenamidone 

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

 

Mammalian LD50 (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 LD50 (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 LD50 (mg/kg bw) 2000 

Enter Mineau Scaling Factor 1.15 

Enter Tested Bird Weight (kg) 0.178 

Mammal 

Enter Lowest Rat Oral LD50 (mg/kg bw) 2028 

Enter Lowest Rat Inhalation LC50 (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/m3) 4.36E-05 

Maximum 1-hour Vapor Inhalation Dose (mg/kg) 5.48E-06 

Adjusted Inhalation LD50 1.15E+01 

Ratio of Vapor Dose to Adjusted Inhalation LD50 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 LD50 2.44E-03 Exposure not Likely Significant 

 

Results Mammalian (0.015 kg ) 

Maximum Vapor Concentration in Air at Saturation (mg/m3) 4.36E-05 

Maximum 1-hour Vapor Inhalation Dose (mg/kg) 6.88E-06 

Adjusted Inhalation LD50 1.25E+02 

Ratio of Vapor Dose to Adjusted Inhalation LD50 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 LD50 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 LD50 >1520 mg/kg bw 45386113 (Acceptable) 

No more than 

slightly toxic 

Freshwater fish Acute 

Rainbow trout 

Oncorhynchus 

mykiss

LC50 >17.2 mg/L 

NOAEC = 17.2 mg/L 

45385730 

(Supplemental) No more than 

slightly toxic 

Freshwater 

invertebrates Acute Water flea Daphnia magna

EC50 >97.4 mg/L 

NOAEC = 97.4 mg/L 

45385725 

(Acceptable) 

No more than 

slightly toxic 

Freshwater plants Acute 

Freshwater algae 

Scenesdesmus 

subspicatus

EC50 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

LC50 >98 mg/L 453857301 

(Acceptable) 

 No more than 

slightly toxic 

Freshwater 

invertebrates Acute Water flea Daphnia magna

EC50 > 100.8 mg/L 45385727 

(Acceptable) 

Practically 

non-toxic 

Freshwater 

plants Acute 

Freshwater algae 

Scenesdesmus 

subspicatus

EC50 >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

LC50 >2.0 mg/L 45385801 

(Supplemental) 

No more than 

moderately 

toxic -- 

Freshwater 

invertebrates Acute Water flea Daphnia magna

EC50 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

EC50 >5.5 mg/L MRID 45385726 

(Supplemental) 

No more than 

moderately 

toxic