UNITED STATES E N V I RONMENTA L PROTECT I O N AGE N CY WASHINGTON D.C., 20460 OFF I CE OF CHEMICAL SAFETY AND POllUT I ON PREVENTION

PC Code : 113202 DP Barcode: 0423285 Date : March 3, 2015

MEMORANDU M

Subject : Registration Review: Problem Formulation for the Env ir onmental Fate
, Ecological Risk, Endangered Species, and Drinking Water Assessments f or Famoxadone

To :

From: Christina Scheltema
, Chemical Review Manager Avivah Ja k ob, l'eam Leader Neil Anderson, Acting Branch Chief Risk Management and Implementation Branch 3 Pesticide Re

- Evaluation Division (7508P) /''

Freeborn Jewett, M

. S., Biologist Christopher M

. Koper
, M

. S

. , Chemist Sujatha Sanku l a, Ph.D

. , Branch Chief Environmental Risk Branch I / '**~**

Environmental Fate and Effe c ts Division (7507P)

1

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Table of Contents Executive Summary

................................ ................................ ................................ ................................ ...... 3

Introduction

................................ ................................ ................................ ................................ ................. 4

Conclusions from Previous Risk Assessments

................................ ................................ ............................... 6
Environmental Fate and Transport

................................ ................................ ................................ ............... 7
Receptors

................................ ................................ ................................ ................................ ................... 1 0 Exposure Pathways of Concern

................................ ................................ ................................ ................... 18
Analysis Plan

................................ ................................ ................................ ................................ ............... 19 Endangered Species Assessments

................................ ................................ ................................ .............. 20
Endocrine Disruptor Screening Program

................................ ................................ ................................ .... 2 1
Preliminary Identification of Data Gaps

................................ ................................ ................................ ..... 21
References

................................ ................................ ................................ ................................ .................. 3 4 Appendix A: Famoxadone and its Degradates

................................ ................................ ........................... 3 5
Appendix B: Summary of Registered Uses

................................ ................................ ................................ . 40
Appendix C: Previous Actions

................................ ................................ ................................ .................... 4 2
Appendix D: Inputs and Outputs from SIP

................................ ................................ ................................ . 4 4
Appendix E: Inputs and Outputs from STIR

................................ ................................ ................................ 4 5
Appendix F: Bibliography

................................ ................................ ................................ ........................... 4 6
Appendix G: Health Effect Division’s MARC Document

................................ ................................ ............. 5 43

1. Executive Summary:
The Environmental Fate and Effects Division (EFED) has completed the problem formulation for the environmental fate, ecological risk, endangered species, and drinking water exposure assessments to be conducted as part of the Registration Review of the fung icide famoxadone. Famoxadone is an oxazolidinedione

- class fungicide that is active against germination and mycelial growth of select fungi species. Functioning as the first stage of the risk assessment process for Registration Review, this problem formulat ion provides an overview of what is currently known about the environmental fate and ecological effects associated with famoxadone and its degradates. It also describes the preliminary ecological risk hypothesis and analysis plan for evaluating and charact erizing drinking water exposure and risk to non

- target species and the environment in support of the Registration Review of famoxadone. This document also recommends studies to be included in a data call

- in (DCI) to address uncertainties surrounding the en vironmental fate and potential ecological effects of famoxadone.

a. Data Gaps Data gaps in the environmental and ecological effects sections are identified and included in the data gaps section in Tables 7

- 10 . Below is a brief summary:

Fate d ata gaps for f amoxadone (parent) are:

 OCSPP 835.4200: Anaerobic Soil Metabolism: 3 additional soils

 OCSPP 835.4300: Aerobic Aquatic Metabolism: 1 additional sediment

- water system

 OCSPP 835.4400: Anaerobic Aquatic Metabolism: 2 sediment

- water systems

 OCSPP 860.1380: Stor age S tability in soil and water

 OCSPP 850.7100: ECM/ILV: Method and independent validation in soil

Ecotoxicity data gaps for famoxadone (parent) are:

 Non Guideline Tier I : Honeybee a cute a dult o ral t oxicity

 Non Guideline Tier I: Honeybee adult chronic ora l exposure

 Non Guideline Tier I: Honeybee larval acute oral exposure

 Non Guideline Tier I: Honeybee larval chronic oral exposure

 Non

- Guideline Tier II: Semi

- field testing for honeybees

 Guideline 850.3040: Field testing for pollinators

 Guideline 850.2100: Avian acute oral toxicity

- passerine species

 Non

- Guideline : Whole sediment chronic toxicity test for freshwater invertebrates, using Chironomus dilutes

, and f reshwater amphipod Hyalella Azteca

 Non

- Guideline : Whole sediment chronic toxicity test for estuarine/marine invertebrates, using estuarine/marine amphipod Leptocheirus plumulosus

Ecotoxicity data gaps for famoxadone degradates are:

 S tudies were submitted by the Registrant upon request that assess the toxicity of the major degradates of famox adone to Daphnia magna . These studies will be evaluated by the Agency, and if they are found not to be scientifically sound, they will be considered data gaps. Toxicity studies for three of the degradates were not included in this group of studies. Details of these studies are available in Table 10.

 Guideline 850.1010: 48

- Hour Limit Test of IN

- KZ007 to Daphnia magna

 Guideline 850.1010: 48

- Hour Limit Test of IN

- MN467 to Daphnia magna

 Guideline 850.1010: 48

- Hour Limit Test of IN

- MN968 to Daphnia magna4 b. Uncertainties

 There is limited toxicity data available for the 9 degradates of famoxadone, although preliminary, unreviewed studies on Daphnia magna indicate that these degradates are considerably less toxic than the parent, famoxadone.

 The label currentl y lists the number of applications for spinach in terms of cropping cycles and there may be more than one cropping cycle per season for these crops depending on the geographic region. In the absence of this information, a maximum of 8 annual applications will be assumed.

2. Introduction

The purpose of this problem formulation is to provide an under standing of what is known about the environmental fate and ecological effects of famoxadone considering its currently registered uses. This document will provide a plan for analyzing data relevant to famoxadone and for conducting ecological risk, endangered species, and drinking water exposure assessments for its registered uses. T his problem formulation is intended to identify data gaps, uncertainties, and potential assumptions used to address those uncertainties relative to characterizing the ecological risk associated with the registered uses of famoxadone. In addition, the Agen cy has developed the “ Endangered Species Protection Program '' to identify pestici des which may cause adverse impacts on endangered and threatened species, and to implemen t mitigation measures that will eliminate the adverse impacts.

Famoxadone (CAS 131807

- 57

- 3; PC Code 113202) is currently registered for agricultural uses (USEPA 2014a) as a mixture with cymoxanil (PC code 129106) , under the commercial name, Tanos. Tanos i s labeled for aerial
, ground spray , and chemigation at a maximum annual rate of 1.31 lbs famoxadone/A, and a max imum of 8 annual applications. The labeled uses and rates currently listed for Tanos are available in App endix C.

EFED evaluated the most recent ecological risk assessments for famoxadone in association with the updated toxicity, exposure, and usage info rmation to determine if sufficient data are available and if further updates are needed to support r egistration review. Recent risk assessments include a 2 008 assessment for the use of famoxadone on leafy greens, bulb vegetables, c ilantro , cranberries, l ea fy Petioles (D 349252 ); as well as a 2006 assessment on grapes, hops, and c aneberries ( D331970 ) . In addition, EFED considered the latest Agency science policies and risk assessment methodologies. The structure of famoxadone , as well as th e chemical names an d structures of major and minor degradates can be found in the chemical identity table located in Appendix A

.
3. Use Characterization

a. Mode of Action

Famoxadone is a non

- systemic, broad

- spectrum fungicide that belongs to the class of chemicals known

as oxazolidinediones. Following famoxadone application, sporangial differentiation and release of
zoospores is inhibited. Upon higher application rates, mycelial growth and germination of sporangia are reduced (Andrieu et al., 2001).

b. Overview of Pesticide Us e and Usage5

The Biological and Economic Analysis Division (BEAD) provided a Screening Level Usage Analysis (SLUA) to provide estimates of the actual usage of famoxadone on a gricultural crops (USEPA, 2014). All registered uses of famoxadone are agricultural and include crops such as caneberries, fruiting, leafy, and bulb vegetables, cucurbits, potatoes, hops, and grapes to control and/or manage fungal and bacterial disease. Famoxadone is registered for the control of downy mildew and suppression of bacteria l soft rot and Xanthomonas blight of bulb vegetables; leaf spot diseases of caneberries; Alternaria leaf blight, anthracnose, and bacterial fruit blotch of cucurbits; downy mildew of grapes, hops and leafy vegetables; early and late blight of potatoes, and various fungal diseases of tomatoes. It is primarily used on potatoes, cucumbers, tomatoes and peppers as shown in Table 1. In recent years (2008

- 2012), approximately 41,000 lbs a.i. were used to treat an average of 352,000 acres in the U.S. at an overall average application rate of 0.12 lb a.i. per acre. The predominant uses of famoxadone in terms of percent crop treated are cucumbers (25%), caneberries (15%), and potatoes, onions, peppers, and pumpkin (10% each). Highest total application in terms of acr es treated was to potatoes (10,000), cucumbers (8,000), tomatoes (6,000) and peppers (3,000). With the exception of the manufacturing process, all registered uses of famoxadone are in the form of a mixture known as Tanos (25% famoxadone, 25% cymoxanil) for mulated as water dispersible granules (dry flowable) applied via ground, air, or chemigation equipment. Appendix B summarizes the labeled uses of famoxadone. The highest registered application rate is for bulb onions, bulb vegetables, and spinach at a maxi mum annual application rate of 1.31 lbs a.i./A. Appendix B presents the agricultural uses and corresponding application rates (single and maximum), application interval, and methods of application that will be considered in the Registration Review risk ass essment. In the event that a parameter is not specified on the label, the Agency m ay make conservative assumptions to estimate environmental exposure. In the case of the labeled use of tanos on spinach, the maximum application rates are written in terms of applications per cropping cycle. In the absence of these data, the 8 applications per cropping season written on the label will be assumed to be the maximum number of annual applications as well.

Table 1 : Estimates of the Actual Usage of Famoxadone on A gricultural Crops (USEPA, 2014).

Crop Average

Annual Lbs. A.I. Percent Crop Treated

Average Maximum

Caneberries 1,000 15 25 Cantaloupes <500* 5 10 Cucumbers 8,000 25 50 Grapes, wine <500 <1 <2.5
Lettuce 2,000 5 10
Onions 2,000 10 15 Peppers 3,000 10 20
Potatoes 10,000 10 20 Pumpkins 1,000 10 15 Spinach <500 <2.5 <2.5 Squash 1,000 10 25
Tomatoes 6,000 5 25 Watermelons 1,000 <2.5 5 *All numbers rounded.6

4. Conclusions from Previous Risk Assessments

a. Previous Ecological Risk and Drinking Water Assessments

Famoxadone was first registered in July of 2003

. The Agency has conducted multiple risk assessments on famoxadone that serve as a basis for this scoping document, including 3 N ew U se assessments and one S ection 18 A ssessment. The ecological ri sk and drinking water assessments conducted by EFED are summarized in Appendix C

. The most recent assessment was carried out in 2008 ( D349252 ) on b ulb vegetables group 3, leafy greens subgroup 4A, leaf petioles subgroup 4B, c ilantro and c a n e berry subgroup 13A ; the risk concerns identified based on the highest application rate (bulb vegetables) were:

 Chronic risk to mammals ( L isted and non

- listed)

 Chronic risk to birds (L isted and non

- listed)

 Acute risk to freshwater fish ( Li sted and non

- l isted)

 Acute r isk to freshwater invertebrates (Listed and non

- listed)

 Chronic risk to freshwater invertebrates ( Listed and non

- listed)

 Acute r isk to estuarine/marine fish (Listed and non

- listed)

 Acute r isk to estuarine/marine invertebrates (Listed and non

- listed)

Previous assessments have also identified risk concerns to the following taxa:

 Acute risk to birds (Caneberry, USEPA 2006)

 Acute risks to mammals (Soybeans, USEPA, 2005)

b. Drinking Water Assessment

The latest drinking water exposure assessment was condu cted in 2008 for famoxadone and its degradates IN

- MN468, IN

- MN467, IN

- MN968, and IN

- JL856 following the total toxic residue (TTR) approach in associa tion with the proposed use s on l eafy g reens subgroup 4A, b ulb v egetables g roup 3,

c ilantro
, c aneberry subgr oup 13A , and l eaf p etioles subgroup 4B (D347671, D347674).

c. Clean Water Act Programs

Famoxadone is not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act. No Total Max imum Daily Load (TMDL) criteria have been developed for famoxadone . Aquatic benchmarks have been e stablished for famoxadone and are avai lable at http://www.epa.gov/oppef ed 1/ecorisk_ders/aquatic_life_benchmark.htm

. Any data submitted or otherwise located as part of the registratio n review process may be used to update aquatic life benchmarks , if applicable.

5. Environmental Fate and Transport
The major routes of degradation for famoxadone include alkaline

- catalyzed hydrolysis, photodegradation in water and aerobic biodegradation in terrestrial and aquatic environments. Famoxadone does not appear to be persistent in the environment. Under alkal ine conditions the hydrolytic half

- life of famoxadone is on the order of a few hours (MRID 44946336). The aqueous photolysis half

- life is equivalent to 4.6 days of natural sunlight (MRID 44946337). Soil photolysis half

lives from two radiolabels are 9.5 days and 16.2 days (MRID 44946338). Aerobic biodegradation occurs7

faster than anaerobic biodegradation in terrestrial environments with seven aerobic half

- lives ranging from 3.1 days to 38.3 days (MRID 44946339, MRID 44946402)
, compared to 33.5 days and 3 6.1 days for two radiolabels in an anaerobic soil study (MRID 44946404). In addition, three aerobic aquatic half

- lives were less than or equal to 3.5 days (MRID 44946405). No anaerobic aquatic metabolism data has been submitted to the Agency and remains a data gap for registration review

. Famoxadone is expected to possess low mobility in soils based upon Koc values ranging from 3307 to 4030, indicating low potential for leaching into ground water (MRID 44946407, 46350401). Comparing Koc values, famoxad one degradates IN

- KF015 and IN

- JS940 are more mobile than the parent compound, but aerobic soil metabolism studies indicate that these degradates are shorter lived than parent famoxadone (MRID 44946409, 45294102, 45358801). A batch equilibrium study shows the degradate IN

- KZ007 to be less mobile than famoxadone depending on soil type (MRID 45294104).
Terrestrial Field Dissipation (TFD) studies (MRID 44946410, 45294105, 45294106, 45358802) showed movement of parent and residues but none were detected below 15 cm (6 inches). In addition, an aged soil column leaching study showed famoxadone did not leach below the top 5 cm of the soil column (MRID 44946406).
Volatilization is not expected to be an important transport process since famoxadone has a relativel y low vapor pressure and Henry's Law constant. Famoxadone has limited water solubility (52 μg/L at 20 degrees C). A bioconcentration study in bluegill sunfish show s that famoxadone has the tendency to bioconcentrate in aquatic organisms (2584X

- 3425X in w hole fish tissues); however, depuration appears to be rapid (50% elimination rate by day 2 of the depuration period) so it is not likely to bioaccumulate in the food chain (MRID 44946413). The important physical and chemical properties for famoxadone

are summarized in Table 2

.

Table 2 : Nature of the Chemical Stressor
Parameter Value Source/MRID #

Common name Famoxadone

Product Chemistry CAS number 131807

- 57

- 3 Chemical name 3

- anilino

- 5

- methylB5

- (4

- phenoxyphenyl)

- 1,3

- oxazolidine

- 2,4

- dione Chemical Class Chemical Category Oxazolidinedione Fungicide
SMILES Notation clcc(Oc2ccccc2)ccclC3(C)C(=O)N(Nc4ccccc4)C(=O)O3 Empirical formula C 22 H 18 N 2 O 4

Structure

Molecular Mass 374.4 g/mole Water Solubility 0.052 mg/L at 20 oC Tomlin, 20038

Parameter Value Source/MRID #
Vapor pressure (20  C) 4.8 x 10
- 9 mm Hg Tomlin, 2003 Henry’s Law Constant 4.5 x 10
- 8 atm m3/mol Calculated 1 Octanol/water partition coefficient (log Kow) 4.65 Tomlin, 2003

Hydrolysis (t 1/2) pH 5 = 31 days at 25  C pH 7 = 2.7 days at 25  C pH 9 = 1.8 hours at 25  C 44946336

Direct Aqueous Photolysis (t 1/2 ) 4.6 days 44946337

Soil Photolysis (t 1/2 ) 9.5 days 16.2 days 44946338

Aerobic Soil Metabolism

(t 1/2 ) Famoxadone (parent) 28.3 days (loamy sand) 38.3 days (sandy loam) 4.5 days (silt loam) 6.1 days (silt loam 10 ◦C) 3.1 days (silt loam 20 ◦C) 8.9 days (sandy loam) 7.6 days (sandy loam) 44946339

44946339

44946339

44946339

44946339

44946402

44946402
IN

- KF015 (degradate) 1.2 days 44946409

IN

- JS940 (degradate) 20.4 hours (sandy clay loam) 24.0 hours (loam) 5.0 hours (sandy loam) 45294102

IN

- KZ007 (degradate) 2.5 days (sandy clay loam) 18.3 days (loam) 11.8 days (sandy loam) 45358801

Anaerobic Soil Metabolism (t 1/2 ) 33.5 days 36.1 days 44946404

Aerobic Aquatic Metabolism (t 1/2 ) 1.2 days (pH 7.1) 1.4 days (pH 7.7) 3.5 days (pH 7.7) 44946405

Anaerobic Aquatic Metabolism (t 1/2 ) Data Gap

--9

Parameter Value Source/MRID #

Soil Partition Coefficient (Koc) Famoxadone (parent) 3890 mL g o.c.

- 1 for Sandy Soil 3330 mL g o.c.

- 1 for Sandy Loam 4030 mL g o.c.

- 1 for Sandy Clay Loam 3307 mL g o.c.

- 1 for Silty Clay Loam 44946407 44946407 44946407 46350401
IN

- KF015 (degradate) 130 mL g o.c.

- 1 for Silty Clay Loam 210 mL g o.c.

- 1 for Loamy Sand 1300 mL g o.c.

- 1 for Silt Loam 380 mL g o.c.

- 1 for Sandy Loam 44946409

IN

- JS940 (degradate) 515 mL g o.c.

- 1 for Sandy Clay Loam 33 mL g o.c.

- 1 for Sandy Loam 591 mL g o.c.

- 1 for Loam 179 mL g o.c.

- 1 for Loam 45294103

IN

- KZ007 (degradate) 34,423 mL g o.c.

- 1 for Sandy Clay Loam 11,331 mL g o.c.

- 1 for Loam 7,828 mL g o.c.

- 1 f or Loam 1,238 mL g o.c.

- 1 for Sandy Loam 45294104

Aged Soil Column Leaching Famoxadone did not leach beyond the top 5 cm of the soil column. 44946406

Terrestrial Field Dissipation (DT 50 ) 6.5 days (MD silt loam) 12 days (FL sand) 28 days (CA silty clay loam) 19.7 days (MN loam) 30.5 days (CA sandy loam) 26.4 days (IL clay loam) 10.1 days (WA sand) 12.5 days (Canadian loamy sand) 32.9 days (Canadian gravelly fine sandy loam) 44946410 44946410 44946410 45294105 45294105 45294106 45294106 45358802 45358802

Bioaccumulation in Fish (BCF) Radiolabel 1

971X in edible tissues 3327X for inedible tissues 2584X for whole fish 50% eliminated by day 2 of the depuration period Radiolabel 2 1286X in edible tissues 3608X for inedible tissues 3425X for whole fish 50% eliminated by day 2 of the depuration period 44946413

1 = Henry’s Law (atm

- m3/mole) = (VAPR/760)/(SOL/MWT), where VAPR is vapor pressure in torr, MWT is molecular weight in g/mol, and SOL is the solubility in water in mg/L.

a. Transformational Products10

Eight degradates were identified for famoxadone. They are IN

- JS940, IN

- H3310, IN

- JL856, IN

- MN468, IN

KF015, IN

- KZ007, IN

- MN467, and IN

- MN968. In soil, t he dominant metabolites of fam oxadone are IN

K Z007 and IN

- JS940. IN

- MN467 and IN

- MN468 were al so detected in small amounts (<2% of applied radioactivity). A soil photolysis study detected IN

- KF015 (max. 22% on day 1; degrades further to IN

JS940 which degrades to IN

- H3310), IN

- H3310 (increased to 27%), IN

- MN468 (increased to 13%), IN

MN467 (increa s ed to 18%) and IN

- JS940 (<7%). In water, several degradation products were formed due to hydrolysis, but only IN

- JS940 and IN

- H3310 were stable. In water

- sediment studies IN

- JS940 reached a maximum of 20.5 % in water and 3.5 % in sediment on day 3, wherea s IN

- H3310 reached a maximum of 2.3 % in water and 10.7 % in sediment on day 7.

For the ecological risk assessment, the parent famoxadone along with the following degradates IN

JS940, IN

- H3310, IN

- JL856, IN

- MN468, IN

- KF015, IN

- KZ007, IN

- MN467 , and IN

- MN 9 68 will be assessed. The residues of concern will be determined after the degradate toxicity data (data called

- in) has been reviewed by the Agency.

For the drinking water assessment, parent famoxadone including the degradates IN

- MN467, IN

- MN468, IN

- JL856 , and IN

- MN968 will be assessed together following the total toxic residue (TTR) approach following the recommendation of HED’s MARC Decision memorandum. The memorandum along with the rationale for selection of degradates can be found in Appendix G.

6. Receptors
Consistent with the process described in the Overview D ocument (USEPA, 2004), the risk assessment for famoxadone relies on a surrogate speci es approach. Toxicological data generated from surrogate test species, which are intend ed to be representa tive of broad taxonomic groups, are used to extrapolate the potential effects on a variety of species (receptors) included under these taxonomic groupings.
Acute and chronic toxicity data from studies submitted by pesticide registrants along with the avail able open literature will be used to evaluate the potential direct and indirect effects of famoxadone to aquatic and terrestrial receptors. This includes toxicity on the technical grade active ingredient, degradates, and when available, formulated products (e.g., "Six

- Pack" studies). The open literature studies are identified through EPA's ECOTOXicology (ECOTOX) database which employs a literature search engine for locating chemical toxicity data for aquatic life, terrestrial plants, and wildlife. Data from an ECOTOX run for famoxadone will be evaluated for possible quantitative and/or qualitative inclusion in the risk assessment in support of Registration Review.

Table 3 provide s a summary of the terrestrial and aquatic toxicity endpoints used to chara cteri ze the potential acute and chronic ecological effects of famoxadone

. Table 4 list the toxicity endpoints for formulations of famoxadone and cymoxanil. These formulations are intended to test the toxicity of the typical end

- use product (TEP) Tanos ® ( formula tion containing 25% famoxadone and 25% cymoxanil). Available data on Tanos ® sug gest that technical grade famoxadone is similar in toxicity to famoxadone in the formulation, except in the case of acute toxicity to mammals, where the T anos ® TEP is more toxi c

. Toxicity endpoints for five of the major degradation products IN

- JS940 , IN

- H3310 , IN

- JL856 , IN

- MN468 , IN

- KF015 are listed in Table 5

. Preliminary review of these studies indicates that the toxicity of famoxadone degradates is equally or less toxic than the parent compound. Additional detail is included in the tables.

a. Effects to Terrestrial and Aquatic Organisms11

Based on terrestrial tox icity endpoints, famoxadone is practically non

- toxic to birds, mammals, honey bees and terrestrial plants. In terms of chronic toxicity, the two avian test species bobwhite quail and mallard were equally sensitive while the rat was used as a surrogate spe cies for all mammalian taxa. As a result these endpoints should be considered in future risk assessments. Famoxadone is very highly toxic to freshwater fish, estuarine and marine fish, estuarine/marine invertebrates, and freshwater invertebrates. The most sensitive freshwater fish species is the rainbow trout, while the most sensitive estuarine/marine fish spe cies is the sheepshead minnow. The most sensitive estuarine/marine invertebrate species to acute exposure to famoxadone was the eastern oyster, while the water flea was the most sensitive freshwater invertebrate species to acute exposure.

The most sensiti ve aquatic plant species is the freshwater diatom, Navicula pelliculosa . Toxicity endpoints were non

- definitive for the aquatic vascular plant Lemna gibba and the m arine d iatom Skeletonema costatum

.

Table 3 : Famoxadone TGAI Toxicity Data for Terrestrial T axa Taxa Study Type Species Toxicity Value & Category MRID & Status Endpoints Affected

Birds Acute Oral

850.2100 Northern

Bobwhite Colinus virginianus LD 50 >2250 mg a.i./kg

- bw

NOEL=2250 mg a.i./kg

- bw

Practically Non

- Toxic 44946232 Acceptable No effects

Acute Dietary 850.2200 Mallard Duck

Anas p latyrhynchos LD 50 >5620 mg a.i./ kg

- diet

NOEL= 5620 mg a.i./ kg

diet

Practically Non

- Toxic 44946234 Acceptable No effects

Acute Dietary 850.2200 Northern

Bobwhite Colinus virginianus LD 50 >5620 mg a.i./L

NOEL = 5620 mg a.i./L 44946233 Acceptable No effects

Chronic Reproduction 850.2300 Northern

Bobwhite Colinus virginianus NOEC = 46 mg a.i/L

LOEC = 252 mg a.i./L 44946235 Acceptable Normal hatchlings,

14

- day survivors

Chronic Reproduction 850.2300 Mallard Duck

Anas pl atyrhynchos NOEC = 46 mg a.i./L

LOEC = 252 mg a.i./L 44946237 Acceptable 14

- day survivors

and viable embryos/ eggs set

Mammals Acute Oral

870.1100 Rat

Rattus norvegicus LD 50 >5000 mg a.i./kg

body weight

Practically Non

- Toxic 44302407 Acceptable No effects

Acute Inhalation 870.1300 Rat

Rattus norvegicus LD 50 = 5.3 mg/L 47419208 Acceptable Weight loss,

Lethargy

Chronic two

generation reproduction 870.4100 Rat

Rattus norvegicus LOAEC = 800 mg a.i./kg

diet NOAEC = 200 mg a.i./kg diet 44302428 Acceptable Decreased glucose

(Males); decreased weight gain, decreased food12 Taxa Study Type Species Toxicity Value & Category MRID & Status Endpoints Affected consumption, decreased food efficiency, mild hemolytic anemia, decreased globulin (females)

Terrestrial invertebrates Acute Oral

adult Non

- guideline (OECD 213) Honey Bee

Apis mellifera LD 50 >1000 mg/kg

NOEC = 1000 mg/kg

Practically Non

- Toxic 44946325 Supplemental Non guideline

Endpoints not valid for risk
assessment as solvent was not used to mix spiked food
source, concentrations
were not measured during experiment N o effects

Acute Contact

Adult 850.3020 Honey Bee

Apis mellifera LD 50 >25.0 μ g a.i./bee

NOEC =25 μ g a.i./bee

Practically Non

- Toxic 44946326 Acceptable No effects

Terrestrial Plants Seedling

Emergence 850.4100 Monocot s

Corn ( Zea mays) , Onion ( Allium cepa)
, Sorghum ( Sorghum bicolor ) , Wheat ( Triticum aestivum ) EC 25 >0.187 lbs a.i./A

NOAEC= 0.187 lbs a.i./A 44946319 Acceptable Mean dry weight,

height

Dicots

Cucumber ( Cucumis sativus ) , Pea ( Pisum sativum )
, Rapeseed ( Brassica napus )
, EC 25 >0.187 lbs a.i./A

NOAEC = 0.187 lbs a.i./A 44946319 Acceptable Mean dry weight,

height13 Taxa Study Type Species Toxicity Value & Category MRID & Status Endpoints Affected Soybean ( Glycine max )
, Sugar Beet ( Beta vulgaris )
, Tomato ( Lycopersicon esculentum ) Vegetative Vigor 850.4150 Monocots

Corn, Onion, Sorghum, Wheat EC 25 >0.187 lbs a.i./A

NOAEC = 0.187 lbs a.i./A 44946319 Acceptable Mean dry weight

Dicots

Cucumber, Pea, Rapeseed, Soybean, Sugar Beet, Tomato EC 25 >0.187 lbs a.i./A

NOAEC = 0.187 lbs a.i./A 44946319 Acceptable Mean dry weight

Freshwater Fish Acute

850.1075 Rainbow Trout

Oncorhynchus mykiss LC 50 = 12 μ g a.i./L

NOEC = 5.2 μ g a.i/L

Very Highly Toxic 44946239 Supplemental

Non

- guideline

Mean measured recoveries low. Endpoints valid for risk
assessment Mortality, dark

coloration, partial loss of equilibrium, and erratic swimmi ng

Chronic (Early Life Stage) 850.1 4 00 Rainbow Trout

Oncorhynchus mykiss NOEL = 1.4 μ g a.i./L

LOEL= 4.1 μ g a.i./L 44946312 Acceptable Percent

abnormalities in surviving fish at 90 days

Estuarine/ Marine Fish Acute

850.1075 Sheepshead

Minnow Cyprinodon variegatus EC 50 = 49.4 μ g a.i./L

NOEC = 27.7 μ g a.i./L

Very highly Toxic 44946309 Acceptable Mortality

Chronic (Early Life Stage) 850.1400 Sheepshead

Minnow Cyprinodon variegatus NOEL = 5.58 μ g a.i./L

LOEL = 11.2 μ g a.i./L 44946314 Acceptable Hatch survival

Estuarine/ Marine Invertebrate Acute

850.1025 Eastern Oyster

Crassostrea virginica LC 50 = 1.6 μ g a.i./L

NOEC = 1.10 μ g a.i./L

Very Highly toxic 44946310 Acceptable Shell deposition

Chronic Life Cycle 850.1350 Mysid Shrimp

Mysidopsis bahia NOEL = 0.830 μ g a.i./L

LOEL = 1.72 μ g a.i./L 44946315 Acceptable Survival of first

generation males and females

Freshwater Invertebrates Acute

850.1010 Water Flea

Daphnia
magna EC 50 = 11.8 μ g a.i./L

NOEC = 3.5 μ g a.i./L 44946307 Supplemental

endpoints can Mortality14 Taxa Study Type Species Toxicity Value & Category MRID & Status Endpoints Affected Very highly Toxic be used for risk

assessme nts 2 Chronic 850.1300 Water Flea

Daphnia
magna NOEC = 0.085 μ g a.i./L

LOEC = 0.29 μ g a.i./L 44946313 Acceptable Number of

Offspring Produced

Whole sediment: Chronic invertebrates Midge:

Chironomus riparius Sediment:

28

- day EC 50 2.73 mg ai/kg NOEC <0.070 mg ai/kg

Pore Water 28

- Day EC 50 =15.04 mg ai/L NOEC <0.55 mg ai/L 44946308 Supplemental: Endpoints can only be used qualitatively

uncertain ty surrounding the amount of famoxadone sorb ed to sediment and amount present in pore water. --

Aquatic Plants Vascular

850.4400 Duckweed

Lemna gibba EC 50 >81 μ g a.i./L

NOAEC = 81 μ g a.i./L 44946320 Acceptable No Effect

Non

- Vascular 850.4500 Marine Diatom

Skeletonema
costatum EC 50 >75 μ g a.i./L

NOEC = 75 μ g a.i./L 44946321 Acceptable No Effect

Non

- Vascular 850.4500 Freshwater

Diatom Navicula pelliculosa EC 50 = 13.5 μ g a.i./L

EC 05 = 2.6 μ g a.i./L 44946323 Supplemental Cell Density

Non

- Vascular 850.4500 Green Algae

Pseudokirchner iella subcapitata EC 50 : 23 μ g a.i./L

NOEC: 3.9 μ g a.i./L 44946322 Acceptable Area U nder Growth

Curve

Non

- Vascular 850.4500 Blue

- Green

Algae Anabaena flos

aquae EC 50 >84.3 μ g a.i./L

NOEC: 42.6 μ g a.i./L 44946324 Acceptable Cell Density and

Growth Rate

b. Toxicity of Famoxadone Formulations
All commercially registered famoxadone formulations consists of famoxadone and cymoxanil, so it is important to compare the toxicity of these two compounds together to determine if synergistic effects are present. Table 4 shows the LC 50 from acute exposur e of famoxadone TEP to various taxa. In the case of rainbow trout (MRID 46144801), the LC 50 value for the formulation (11 μ g a.i./L) is similar to famoxadone TGAI (13 μ g a.i./L ). In both cases, famoxadone is classified as very highly toxic to freshwater fish. The acute oral toxicity of the famoxadone TEP to rats (Female LD 50 = 566 mg/kg

- bw) was found to15

be greater to rats than famoxadone TGAI ( LD 50 >5000 mg a.i./kg

- body weight), while the inhalation toxicity (LC 50 > 5.1 mg/L) was found to be less than that observed for famoxadone TGAI ( LD50= 5.3 mg/L )

.
F amoxadone/cymoxanil T EP exposure to northern bobwhite quails resulted in non

- definitive endpoints (LD 50 : >511 mg famoxadone/kg

- bw ), which was also the case for the T GAI (LD 50 : >2250 mg a.i./kg) . In the case of the honey bee, the LD 50 s for oral and contact or the TEP ( >200 μg famoxadone/bee ) were non definitive and tested at a level lower than the TGAI ( LD 50 >1000 mg/kg ), but there is no evidence of increased toxicity

. With the exception of mammals, there is no indication that TEP is of greater toxicity than famoxadone TGAI for these taxa

. The toxicity o f famoxadone/cymoxanil TEP to terrestrial plants, estuarine/ marine taxa and freshwater invertebrates was not tested and this remains an uncertainty. The registrant is encouraged to submit data that assess the toxicity of famoxadone TEP to aquatic taxa in order to better characterize the risk of this mixture to aquatic ecosystems, but this is not a formal data gap at th is time.

Table 4 : Toxicity Endpoints for Famoxadone TEP Taxnonomic Group Study Type Formulation %famoxadone / %cymoxanil Species Toxicity Value & Category MRID & Status

Freshwater Fish Acute 25%/25% Rainbow Trout Oncorhync hus mykiss Total Formulation

LC 50 : 29.0 μ g /L NOAEC: 14.1 μ g /L

Famoxadone LC 50 : 11 μ g a.i./L NOAEC: 5.7 μ g a.i./L

Very Highly Toxic 46144801 Acceptable

Freshwater Fish Acute 22.7%/30.4% Rainbow Trout Oncorhync hus mykiss LC 50 :

 > 100 μ g formulation/L

 > 22.5 μ g famoxadone/L

 > 30 μ g cymoxanil/L

Very highly toxic 44946302 Supplemental

Scientifically sound,

non

- guideline

Mammals Acute Oral 25%/25% Rat Rattus norvegicus Male LD 50 = 1732 mg/kg

- bw

Female LD 50 = 566 mg/kg

- bw Slightly toxic 44944507 Acceptable

Acute Inhalation 25%/25% Rat Rattus norvegicus LC 50 >5.1 mg/L 44944509 Acceptable

Birds Acute Oral 22.7%/30.4% Northern Bobwhite Colinus virginianus LD 50 :

 >2250 mg formulation/kg

- bw

 >511 mg famoxadone/kg

- bw 44946318 Supplemental

Scientifically sound,

non

- guideline16 Taxnonomic Group Study Type Formulation %famoxadone / %cymoxanil Species Toxicity Value & Category MRID & Status

 >684 mg cymoxanil/kg

- bw

Moderately Toxic

Terrestrial Vertebrates A cute O ral

and C ontact 22.7%/30.4% Honey Bee Apis mellifera Contact L D 50 :

 >200 μ g formulation/bee

 >200 μ g famoxadone /bee Oral LD 50 :

 >200 μ g formulation/bee

 >45.5 μ g famoxadone /bee Practically Nontoxic on an Acute Oral and Contact Basis 46350402 Contact : Acceptable Oral: Supplemental ( Non

- Guideline )

Honey Bee Residue on Foliage 850.3030 25%/25% Honey Bee Apis mellifera TEP: RT 25 <1 Hour

Famoxadone : RT 25 < 1 Hour

No effects 46350403 Supplemental

Endpoints valid for use in risk assessment

c. Toxicity of Famoxadone Degradates
The toxicity of degradates was analyzed with the Ecological Structure Activity Relationship ( ECOSAR ) methods ( http://www.epa.gov/oppt/exposure/pubs/episuite.htm ) . This program attempts to predict toxicity of degradate molecules using known toxicity endpoints of functional groups in the molecule. Shown in Table 5, t his analysis was unable to acc urately predict the toxicity of the parent molecule

. A s a result, no accurate conclusions could be made about famoxadone degradates based on the ECOSAR modeling

.
Table 5: A Comparison of the Predicted Pare nt Famoxadone Toxicity Values as Modeled by ECOSAR Taxa Predicted Toxicity LC 50 (mg/l) Actual Toxicity (mg/l) Freshwater Fish LC 50 =0.703 0.012 Daphnid LC 50 =0.575 0.019 Green Algae LC 50 =0.056 0.023 Mysid Shrimp LC 50 =0.079 0.00083

The degradate IN

- JS940

- 1 was assessed for toxicity to rainbow trout and Daphnia magna , as shown in Table 6 . The rainbow trout study did not fulfil guideline requirements, as it was only conducted at one

tenth of the solubility limit of this compound, but t he non

- definitive endpoint ( >9.0 μ g/L ) for the degradate was far greater than the LC 50 for the parent. Additional endpoints were presented that compared the acute toxicity of famoxadone to the freshwater invertebrate, Daphnia magna to the17

toxicity of five degradates. The degradate toxicity endpoints shown in Table 6 will not be considered valid until the data are evaluated by the Agency , but preliminary observation suggests that these degradates are less toxic than the parent . In the event that these data are not found to be acceptable, the se studies will be treated a s data gaps and the toxicity of famoxadone degradates will be considered to be an uncertainty.

Table 6 : Endpoints for Aquatic Toxicity Studies for Famoxadone Degradate s Taxo nomic Group Study

Type Species Chemical Toxicity Value & Category MRID & Status

Freshwater Fish Acute Rainbow Trout

Oncorhynchus mykiss IN

- JS940

- 1 LC 50 : >9.0 mg a.i./L NOEC: 9.0 mg a.i./L Moderately Toxic 44946306

Supplemental

Non guideline

not tested to full solubility limit

Freshwater Invertebrate Acute Water Flea Daphnia magna Famoxadone 48

- hour EC 50 =0.011 mg a.i./L

Very Highly Toxic 44946307

Supplemental

endpoints can be used for risk

assessme nts

Acute Water Flea

Daphnia magna IN

- JS940 48

- hour EC 50 >9.6 mg a.i./L

Moderately Toxic 44946305

Supplemental

Non

- guideline

tested to one

tenth of the solubility limit. Endpoints can be used to compare toxicity to that of parent. Acute Water Flea

Daphnia magna IN

- H3310 48

- hour EC 50
> 2.7 mg a.i./L

Moderately Toxic In Review

Acute Water Flea

Daphnia magna IN

- JL856 48

- hour EC 50
> 0.19 mg a.i./L

Highly Toxic In Review

Acute Water Flea

Daphnia magna IN

- MN468 48

- hour EC 50
> 0.012 mg a.i./L

Very Highly Toxic In Review18

Taxo nomic Group Study

Type Species Chemical Toxicity Value & Category MRID & Status

Acute Water Flea

Daphnia magna IN

- KF015 48

- hour EC 50
> 8.3 mg a.i./L

Moderately Toxic In Review

d. Ecological Incidents

Three databases, the Ecological Incident Information System or EIIS maintained by the Environmental Fate and Effects Division, the Aggregate Su mmary Module (ASM) of the Office of Pesticide Program's Incident database maintained by the Information Technology and Resource Management Division, and the Avian Incident Monitoring System (AIMS) maintained by the American Bird Conservancy, were searched on October 17 , 2014 to locate incidents resulting from the use of famoxadone.

One incident was recorded in the EIIS database by DuPont, as having occurred on or about May 7, 2010 in Santa Barbara County, California. The report indicated that several fields of celery allegedly exhibited unexpected brown spots on the petioles a few da ys after commercial applications of Tanos was applied to approximately 60 acres of celery crop. There was no mention of residue testing and famoxadone was listed as possibly causing the damage.

In addition to the incidents recorded in EIIS and AIMS, ad ditional incidents are reported to the Agency in aggregated form. Pesticide registrants report certain types of incidents to the Agency as aggregate counts of incidents occurring per product per quarter. Ecological incidents reported in aggregate reports include those categorized as ‘minor fish and wildlife’ (W

- B), ‘minor plant’ (P

- B), and ‘other non

target’ (ONT) incidents. ‘Other non

- target’ incidents include reports of adverse effects to insects and other terrestrial invertebrates. For famoxadone , re gistrants have not reported minor incidents as of October 8, 2014.

7. Exposure Pathways of Concern

In order to estimate risks of famoxadone exposures in aquatic and terrestrial environments, all exposure modeling and resulting risk conclusions will be bas ed on registered labels including maximum famoxadone application rates and intervals cited in Appendix B . EFED's environmental exposure models estimate the potential exposure of plants and animals to pesticide residues in aquatic and terrestrial environmen ts. Some of the aquatic models can also be utilized to estimate pesticide residues in drinking water for use in the dietary exposure models. A more detailed description of aquatic and terrestrial models can be found at the following website: http://www.epa.gov/pesticides/science/models_db.htm

. For terrestrial exposures, the default 35

- day foliar dissipation half

- life will be used. If RQs exceed LOCs, the foliar dissipation half

- life may be refined, as appropriate, using available magnitude of residue studies at the time of the risk assessment.

In addition to modeling estimates, available monitoring data will be evaluated. Monitoring data will include those collected/reported by states as we ll as other federal departments/agencies (e.g.,19

USGS National Water Quality Assessment; http://water.usgs.gov/nawqa ). These monitoring data will be characterized in terms of general statistics including number of samples, frequency of detection, maximum concentration, and mean value of all detections, where that level of detail is available.

The Screening Imbibition Program (SIP v. 1 .0) is used during the problem formulation phase of Registration Review to provide an upper

- bound estimate of exposure of birds and mammals to pesticides through drinking water alone. SIP does not aggregate the drinking water exposure route with other exposure routes ( i.e., dietary, inhalation, dermal). Because avian and mammalian acute toxicity values were non

- definitive and toxicity to these taxa low, SIP was not used, and it is assumed that acute and chronic exposure through drinking water alone would not be a concern for birds and mammals. A full table of inputs and outputs from the model is available in Appendix D.

The Screening Tool for Inhalation Risk (STIR v. 1 .0) is used during the problem formulation phase of Registration Review to assess the potential for exposure to birds and mammals through inhalation. The exposure pathways t hat are assessed by this tool include both droplet inhalation and vapor phase inhalation. STIR is intended to determine if exposure is likely and not whether or not the potential for risk exists. If STIR predicts that exposure is likely, additional inhalat ion data may be necessary to adequately assess risk due to the inhalation exposure pathway. STIR concluded that exposure through inhalation would not be a concern for mammals (acute rat inhalation LC 50 > 5.3 mg/L; MRID 44302410). STIR concluded that exposu re through inhalation could be a concern for birds, but due to the non

definitive endpoints and low avian toxicity, it was determined that additional data were not needed. The result of this analysis is available in Appendix E.

8. Analysis Plan

a. Stressors of Concern

In order to address the risk hypothesis, the potential for adverse effects on the environment is estimated. The use, environmental fate, and ecological effects of famoxadone are characterized and integrated to assess the risks. This analysis plan will be revisited and may be revised depending upon a full review of the data available in the open literature and the information submitted by the public in response to the opening of the Registration Review docket.

i. Ecological Risk Assessment

The stressor of ecological concern for aquatic organisms is famoxadone. Submitted studies indicate that the degradate IN

- JS940

- 1 is less toxic than the parent. Other degradates IN

- KF015 , IN

- H3310 2 , IN

MN468 , and IN

- JL856 have toxicity data that were submitted for review. If these degradates are found to be of similarly low toxicity, the stressor of concern for aquatic organisms will be famoxadone alone.

ii. Drinking Water Assessment

The drinking water assessments conducted to support the Registration Review human health risk assessments of famoxadone will incorporate model ed estimates of famoxadone residues of concern, which are parent com pound famoxadone and degradates IN

- MN468, IN

- MN467, IN

- MN968, and IN

JL856 , in surface and ground waters. The famoxadone residues of concern may be reevaluated pending receipt and review of additional environmental fate a nd toxicity data for famoxadone and its degradates. Famoxadone and degradates IN

- MN468, IN

- MN467, IN

- MN968, and IN

- JL85 6 will be20

assessed together in the drinking water assessment using a total toxic residues (TTR) approach following the recommendation of HED’s MARC Decision memorandum (D288134; Appendix G)

.

b. Measures of Exposure

EFED will use standard available models to evaluate potential exposures to aquatic and terrestrial organisms as described at http://www.epa.gov/pesticides/science/models_db.htm . Pending results of aquatic toxicity studies on the aquatic degradates of famoxadone, these degradates may be included with famoxadone in the residues of concern modeled for aquatic exposure. Because of the lack of available data, famoxadone and the degr adates are assumed to have similar toxicity to terrestrial organisms, and a total toxic residues approach may be used for terrestrial modeling.

Screening level calculations have suggested that chronic drinking water and inhalation exposure pathways may b e significant to birds. These exposure pathways may be further considered at the time of the risk assessment.

i. Available Monitoring Data

The Agency is aware of monitoring conducted by federal and s tate agencies and this information will be considered in t he assessment to the extent that da ta on famoxadone are available.

c. Measures of Effect

Toxicity data presented in Section 3 of this problem formulation will be used to calculate risk quotients

. Any additional information s ubmitted by the registrant or found in the open literature prior to conduct of the risk assessment will also be considered. The open li terature s tud ies are identified using EPA's ECOTOXicology database (ECOTOX) (USEPA, 2007c), which employs a literature search engi ne for locating chemical toxicity data for aquatic life, ter restrial plants, and wi ldlife

. The evaluation of both sources of data can a l so provide insight into th e direct and indirect effects of pesticides on biotic communities from loss of species that are sensitive to the chemicals and from changes in structure and functional characteristics of the affected communities.

9. Endangered Species Assessments

Consistent with EPA’s responsibi lity under the Endangered Species Act (ESA), the Agency will evaluate risks to federally listed threatened and endangered (listed) species from registered uses of pesticides in accordance with the Joint Interim Approaches developed to implement the recomme ndations of the April 2013 National Academy of Sciences (NAS) report, Assessing Risks to Endangered and Threatened Species from Pesticides

. The NAS report outlines recommendations on specific scientific and technical issues related to the development of pesticide risk assessments that EPA and the Services must conduct in connection with their obligations under the ESA and FIFRA. EPA will address concerns specific to famoxadone in connection wi th the development of its final registration review decision for famoxadone

. In November 2013, EPA, the U.S. Fish and Wildlife Service, National Marine Fisheries (the Services), and USDA released a white paper containing a summary of their joint Interim Approaches for assessing risks to listed species from pesticides. These Interim Approaches were developed jointly by the agencies in response to the NAS recommendations, and reflect a common approach to risk ass essment shared by the agencies as a way of addressing scientific differences between the EPA and the Services. Details of21

the joint Interim Approaches are contained in the November 1, 2013 white paper
, Interim Approaches for National

- Level Pesticide Endangered Species Act Assessments Based on the Recommendations of the National Academy of Sciences April 2013 Report.
Given that the agencies are continuing to develop and work toward implementation of the Interim Approaches to assess the potential risks of pesticides to listed species and their designated critical habitat, this ecological problem formulation supporting the Preliminary Work Plan for famoxadone does not describe the specific ESA analysis, in cluding effects determinations for specific listed species or designated critical habitat, to be conducted during registration review. While the agencies continue to develop a common method for ESA analysis, the planned risk assessment for the registratio n review of famoxadone will describe the level of ESA analysis completed for this particular registration review case. This assessment will allow EPA to focus its future evaluations on the types of species where the potential for effects exists, once the s cientific methods being developed by the agencies have been fully vetted. Once the agencies have fully developed and implemented the scientific methods necessary to complete risk assessments for listed species and their designated critical habitats, these methods will be applied to subsequent analyses of famoxadone as part of completing this registration review.

10. Endocrine Disruptor Screening Program

Famoxadone was not included in the first group of 67 chemicals issued an order to conduct Tier 1 EDSP test ing, or the second list of 109 chemicals issued in June, 2014. For additional information the EDSP program, visit http://www.epa.gov/endo/

.

11. Preliminary Identification of Data Gaps

a. Environmental Fate

Table 7 : Data Gaps based on Submitted Environmental Fate Data for Famoxadone
Guideline Description MRID Classification Data Gap? Comments

835.2120 161

- 1 Hydrolysis 44946336 Acceptable No

--

835.2240 161

- 2 Photodegradation in

Water 44946337 Acceptable No

--

835.2410 161

- 3 Photodegradation in

Soil 44946338 Acceptable No

--

835.4100 162

- 1 Aerobic Soil

Metabolism 44946339 44946402 Acceptable

Acceptable No

No --

--22

Guideline Description MRID Classification Data Gap? Comments

835.4200 162

- 2 Anaerobic Soil

Metabolism 44946404 Acceptable Yes These data are required under 40 CFR part 158 for terrestrial outdoor uses. One anaerobic soil metabolism study was submitted. The OCSPP guid eline recommends that these tests be performed with four soils. Because OCSPP uses an upper 90th percentile estim ate of soil metabolism half

- lives based on available study data for modeling purposes, any additional data can reduce uncertainty related to the exposure assessment as well as the half

- life value used in modeling.

835.4300 162

- 4 Aerobic Aquatic

Metabolism 44946405 Acceptable Yes One additional sediment

- water system is needed to fulfill the data requirements as two different sediments with varying organic carbon content and texture are recommended in the OCSPP guidelines.

835.4400 162

- 3 Anaerobic Aquatic

Metabolism -- -- Yes No anaerobic aquatic metabolism data has been submitted to the Agency. Two sediment

- water systems with varying organic carbon content and texture is needed to fulfill the data requirements.

835.1230 Adsorption/Desorption 44946407 46350401 44946409 45294103 45294104 Supplemental

Supplemental Supplemental Supplemental Supplemental No

No No No No Famoxadone Famoxadone IN

- KF015 IN

- JS940 IN

- KZ007

835.1240 163

- 1 Leaching 44946406 Supplemental No Famoxadone23

Guideline Description MRID Classification Data Gap? Comments

835.6100 164

- 1 Terrestrial Field

Dissipation 44946410 45294105 45294106 45358802 Supplemental

Supplemental Supplemental Supplemental No

No No No --

--

--

--

860.1380 Storage Stability in Soil

-- -- Yes Storage stability was typically part of the terrestrial field dissipation study in the past but now has its own guideline number (860.1380) Storage Stability in Water -- -- Yes

850.7100 ECM/ILV

– Soil

-- -- Yes

--

ECM/ILV

– Water 44967204 Acceptable No BEAD performed ILV (D276595)

165

- 4 Bioaccumulation in Fish

(BCF) 44946413 Acceptable No

--

b. Environmental Effects

Table 8 and Table 9 identify ecological effects studies by MRID that offer data for each guideline requirement, as well as study classifications and whether or not further data are needed in order to support risk assessments. A c hronic sediment test (MRID 44946308) has been submitted that observed toxicity effects to the midge Chironomus dilutes
, but endpoints are not valid to quantitatively assess risk because of questions surrounding the concentrations of famoxadone in sediment. T herefore, tests with the C

. dilutes and fres hwater amphipod Hyalella azteca are needed. A study with C. dilutes has been requested and is due on 6/30/2015. The estuarine/marine amphipod Leptocheirus plumulosus is requested because estuarine/marine invertebrate endpoints are more sensitive than fresh water invertebrate endpoints (11.8 μg/L vs. 3.76 μg/L). A tiered approach using toxicity data from sub

- chronic (10

- day) sediment toxicity tests with the three species may be used to determine which species should undergo chronic toxicity testing.

Table 8 : Data Gaps based on Submitted Aquatic Ecological Effects Data for Famoxadone OCSPP Guideline Data

requirement Submitted

Studies MRID Study

Classifications Data Gap? Comments

850.1010 Freshwater

Invertebrate Acute Toxicity 44946307 Supplemental No Generally scientifically sound, and study deviations do not affect the endpoints 850.1025 850.1035 850.1045 850.1055 Estuarine/Marine

Invertebrate Acute Toxicity 44946310 Acceptable Acceptable No

--24

OCSPP Guideline Data

requirement Submitted

Studies MRID Study

Classifications Data Gap? Comments

850.1075 Freshwater Fish

Acute Toxicity 44946239

44946301 Supplemental

Acceptable No Endpoints for rainbow trout study show toxicity effects despite low mean

- measured concentrations and these endpoints are valid for risk
assessment.

850.1075 Estuarine/Marine

Fi sh Acute Toxicity 44946314 Acceptable No

--

850.1300 Freshwater

Invertebrate Life Cycle 44946313 Acceptable No

--

850.1350 Estuarine/Marine

Invertebrate Life Cycle 44946315 Acceptable No

--

850.1400 Freshwater Fish

Early

- Life Stage 44946312 Acceptable No

--

850.1400 Estuarine/Marine

Fish Early

- Life Stage 44946309 Acceptable No

--

Non

- Guideline Whole sediment:

chronic invertebrates freshwater and marine 44946308 Supplemental Yes A c hronic sediment tests with the midge Chironomus dilutes has been provided but endpoints are not valid to quantitatively assess risk because of questions surrounding the concentrations of famoxadone in sediment ; studies with the midge Chironomus dilutes and freshwater amphipod Hyalella azteca and the estuarine/ marine amphipod Leptocheirus plumulosus are

r equested because :

i. The estimated environmental concentration (EEC) in sediment is > 0.1 of the acute LC50/EC50 values; ii. The half

- life of the pesticide in sediment isf > 10 days in either the aerobic soil or aquatic metabolism studies and if any of the following exist:

• The soil partition coefficient (Kd) is ≥ 50

• The log Kow is ≥ 3, or

• The Koc is ≥ 1,00025

OCSPP Guideline Data

requirement Submitted

Studies MRID Study

Classifications Data Gap? Comments

Aerobic soil metabolism studies measured a maximum half

- life o f 38.3 days in sandy loam soil (MRID 44946339). Modeling via PRZM/EXAMS (D349252) indicates aquatic EECs of at least 1.609 μg/L which is approximately 0.13 of the LC50 of 11.8 μg/L for D. magna (MRID 44946307); the log Kow and Koc of famoxadone are 4.65 an d 3307

- 4030 mL/g, respectively

. 850.1500 Fish Life

- Cycle 44946314 Acceptable No

-- 850.4400 Aquatic Plant

Toxicity Test using Lemna spp. 44946320 Acceptable No

--

850.4500 Algal Toxicity 44946321 44946323 44946322 Acceptable

Acceptable Acceptable No

--

850.4550 Cyanobacteria 44946324 Acceptable No

--

Table 9: Data Gaps based on submitted Terrestrial Effects Data for Famoxadone OCSPP Guideline Data

requirement Submitted

Studies (MRID) Study

Classifications Data

Gap? Comments

850.2100 Avian Acute Oral

Toxicity (Upland
game or waterfowl species) 44946232 Acceptable No

--

850.2100 Avian Acute Oral

Toxicity (Passerine species) (none) N A Yes M easures of effect from a non

passerine species could potentially underestimate famoxadone toxicity to passerine species, consequently, additional information on famoxadone toxicity to a passerine species is needed to reduce the uncertainty created by this analysis . These studies are now required under the most recent 40 CFR Part 158 850.2200 Avian Dietary

Toxicity 44946234

44946233 Acceptable

Acceptable No

--26

OCSPP Guideline Data

requirement Submitted

Studies (MRID) Study

Classifications Data

Gap? Comments

850.2300 Avian

Reproduction 44946235

44946237 Acceptable

Acceptable No

--

850.3020 Honey Bee Acute

Adult Contact Toxicity 44946326 Acceptable No

--

Non

Guideline (OECD 213) Tier I

- Honeybee

Acute Adult Oral Toxicity 44946325 Supplemental Yes The study was classified as supplemental , but the endpoints may only be used to qualitatively assess risk because famoxadone concentrations in the food were not measured after mixing. T he highest test concentration s (1000 mg/L) were well above the limit of solubility (49 μ g/L) for this chemical. Non

Guideline Tier I

- Honeybee

A dult C hronic O ral E xposure (none) NA Yes This study estimates the exposure to adult bees resulting from visits
to contaminated flowers over an extended period of time or through consumption of contaminated food in the hive. Non

Guideline Tier I

- Honeybee

Larval C hronic E xposure (none) NA Yes This stud y help s characterize the effect s of repeated exposure of the brood to pesticides that may enter the hive and be stored in food sources such as pollen, honey, royal or brood jelly. Non

Guideline Tier I

- Honeybee

Larval Acute E xposure (none) NA Yes This stud y help s characterize the effe ct of acute exposure of the brood to pesticides that may enter the hive and be stored in food sources such as pollen, honey, royal or brood jelly. 850.3030 Honey Bee

Residue on Foliage 46350403 Supplemental No This study was carried out using the TEP

Non

Guideline Semi

- Field

Testing for Honeybees (none) NA Yes If risks are identified from Tier I risk estimation for honeybees, then Tier II risk estimations may need to be called in to identify more targeted risk mitigation options 850.3040 Field Testing for

Pollinators (none) NA Yes If risks are identified from Tier I risk estimation for honeybees,27

OCSPP Guideline Data

requirement Submitted

Studies (MRID) Study

Classifications Data

Gap? Comments

then Tier II risk estimations may need to be called in to identify more targeted risk mitigation options 850.4100 Seedling

Emergence and Seedling Growth 44946319 Acceptable No

--

850.4150 Vegetative Vigor 44946319 Acceptable No

--

T he following studies shown in Table 10 were recently submitted by the Registrant and are currently under review. These compare the toxicity of famoxadone to that of its major degradate compounds in Daphnia magna . If these studies are found not to be scientifically valid and do not meet OSCPP guideline requirements, then the y will be treated as data gaps.

Table 10: Data Gaps for Famoxadone Degradates OCSPP Guideline Data requirement Submitte d Studies (MRID) Study

Classifications Data

Gap? Comments

850.1075 Acute Toxicity to

Freshwater Fish IN

JS490 44946306 Supplemental No

--

850.1010 48

- Hour Limit Test of

IN

- JL856

- 1 to Daphnia magna 44946305 Supplemental No Non

- guideline

- tested to one

tenth of the solubility limit. Endpoints can be only be used to compare degradate toxicity to that of parent. 850.1010 48

- Hour Limit Test of

IN

- JL856

- 1 to Daphnia magna In Review In Review Yes

These studies have been submitted to the Agency for review. If they are found not to be scientifically sound, they will be considered data gaps. 850.1010 48

- Hour Limit Test of

IN

- MN468

- 0 to Daphnia magna In Review In Review Yes

850.1010 48

- Hour Limit Test of

IN

- KF015 to Daphnia
magna In Review In Review Yes

850.1010 48

- Hour Limit Test of

IN

- H3310 to Daphnia
magna In Review In Review Yes

850.1010 48

- Hour Limit Test of

IN

- KZ007 to Daphnia
magna (n one ) NA Yes Major degradate

- Observed in aerobic soil metabolism study (MRID 44946339) up to 16.2% after 4 days, degrades to 9.8% after 118 days.28

OCSPP Guideline Data requirement Submitte d Studies (MRID) Study

Classifications Data

Gap? Comments

850.1010 48

- Hour Limit Test of

IN

- MN467 to Daphnia magna (n one ) NA Yes Major degradate

- Observed in photolysis study (MRID 44946338) up to 18.3% after 7 days, degrades to 10.2% after 15 days. 850.1010 48

- Hour Limit Test of

IN

- MN968 to Daphnia magna (n one ) NA Yes Major degradate

- Observed in hydrolysis study (MRID 44946336) up to 39.9% AR after 4 hours.

Explanations for non - guideline data requirements are below:

Study Title: Whole S ediment: C hronic Invertebrates

- F reshwater and M arine Rationale for Requiring the Data No chronic sediment toxicity tests for freshwater or marine invertebrates have been submitted to satisfy the Agency’s updated data requirements for outdoor uses in 40 CFR Part 158 (October 26, 2007). Benthic organisms may be exposed to run

- off or spray dri ft from applications used in terrestrial uses. Chronic sediment invertebrate toxicity data are required if: i. T he estimated environmental concentration (EEC) in sediment is > 0.1 of the acute LC50/EC50 values; ii. T he half

- life of the pesticide in sedimen t is > 10 days in either the aerobic soil or aquatic metabolism studies and if any of the following exist:

• The soil par tition coefficient (Kd) is ≥ 50

• The log Kow is ≥ 3 , or

• The Koc is ≥ 1,000

Aerobic soil metabolism studies measured a maximum half

- life of 38.3 days in sandy loam soil (MRID 44946339). Modeling via PRZM/EXAMS (D349252) indicates aquatic EECs of at least 1.609 μg/L which is approximately 0.13 of the LC50 of 11.8 μg/L for D. magna (MRID 44946307); the log Kow and Koc of famoxadone are 4.65 and 3307

- 4030 mL/g, respectively. Chronic sediment tests with the midge Chironomus dilutes has been provided
, but endpoints are not valid to quantitatively assess risk because of questions surroun ding the concentrations of famoxadone in sediment; A follow up study has been requested and is due on 6/30/2015. Studies with the freshwater amphipod Hyalella azteca and the estuarine/marine amphipod Leptocheirus plumulosus are needed. General information and overall guidance is available in the OPPTS 850.1000 guideline 1

.
In some situations, a tiered testing strategy may be considered for requesting chronic sediment
t oxicity testing . In this approach, sediment toxicity testing would f irst be conducted with the aforementioned species using the subchronic (10

- d) sediment toxicity test guidelines (OSCPP 850.1735 and 850.1740). Then, pending a comparison of estimated environmental concentrations (EEC) in sediment and pore water with toxici ty results from the 10

- d sediment toxicity studies, the need for one or more chronic sediment toxicity studies would be determined. This tiered testing approach has the potential advantage of reducing the number of chronic (life cycle) studies that would b e needed when results of the 10

- d (subchronic) tests in conjunction with sediment EECs29

indicate chronic testing is not likely to alter risk assessment conclusions. In some cases, however, this tiered testing approach may result in the conduct of both a 10

- d (subchronic) and a chronic (life cycle) study.

Practical Utility of the Data How will the data be used? The objective of a sediment test is to dete rmine whether chemicals in sediment are harmful to or are bioaccumulated by bent hic organisms. The tests can be used to measure inter active toxic effects of complex chemical mixtures in sediment. These data are used to determine definitive NOEC and LOEC values (typically normalized to organic carbon content for organic test substances ) for survival, growth and reproduction of technical grade active ingredient (TGAI) to freshwater midges, freshwater amphipods and estuarine/marine amphipod s . Data obtained from this study will be used in characterizing risk to sediment

- dwelling aquatic invertebrates from chronic exposure of famoxadone

. How could the data impact the Agency’s future decision

- making? If the data indicates that registered famoxadone uses may pose a risk of adverse effects to non

target benthic organisms above the Agency Lev el of Concern, the Agency may explore decision options to mitigate this risk. The lack of these data will limit the flexibility the Agency and registrants have in coming into compliance with the Endangered Species Act, and could result in use restrictions for famoxadone which may otherwise be avoided, or which are unnecessarily severe.

[ 1 ] http://www.epa.gov/opptsmnt/pub s/frs/publications/OPPTS_Harmonized/850_Ecological_Effects_Test_Guidelines/Drafts/850

- 1000.pdf
Study Title: Tier I

- Honey bee Adult A cute O ral T oxicity Rationale for Requiring the Data Bees can be exposed to pesticides through multiple pathways including contact with sprays and dusts and through ingestion of residues in food/water (e.g., pollen/nectar and water used to maintain colony temperature). Based on the recommended application m ethods for famoxadone
, worker bees foraging on flowers for pollen and nectar can be exposed to residues in pollen and nectar through direct contamination of these matrices by ground sprayer, aerial equipment and chemigation (USEPA, 2014d.) . EPA guidance 1 o n assessing the risk of pesticides to bees identifies a suite of laboratory

- based studies intended that serve as the foundation for screening chemical for potential acute and chronic effects to individual adult and larval bees. The acute oral toxicity stud y with adult bees provides median lethal dose (LD 50 ) v alue for honey bees ( A. mellifera ) based on potential routes of acute oral exposure. Practical Utility of the Data How will the data be used? These data are used in conjunction with acute contact LD 50 data obtained through OCSPP 850.3020 to estimate the acute toxicity of technical grade active ingredient (TGAI) to individual young adult honey bees. The studies also provide slopes for the dose

- response curves that can in turn be used for estimating the l ikelihood of individual effects and sublethal effects observed in the study will be used to further characterize effects observed following a single exposure to the technical grade material. Data obtained from this study will be used in estimating acute ri sk to individual adult bees.

How could the data impact the Agency’s future decision

- making? In t he absence of these data, honey bee oral toxicity data for surrogate pesticides

– starting with data for closely related pesticides and proceeding to data for less related pesticides

– may be used to30

characterize the oral toxicity of famoxadone to honey bees. Risk estimates based on these data will be considered along with other lines of evidence to determine whether higher

- tier studies are needed at the whole colony level. [1] USEPA. 1996. Residue Chemistry Test Guidelines OPPTS 860.1900 Field Accumulation in Rotational Crops. EPA 712

- C

- 96

- 189. file:///C:/Users/tsteeger/Downloads/EPA

- HQ

- OPPT

- 2009

- 0155

- 0019.pdf (last accessed 06/01/2104)

Study Title: Tier I

- Adult Honey Bee Chronic Oral Toxicity Rationale for Requiring the Data Bees can be exposed to pesticides through multiple pathways including long term ingestion of residues in food/water (e.g., pollen/nectar and water used to maintain colony temperature). Worker bees foraging on flowers for pollen and nectar can be repeatedly exposed to residues in pollen and nectar through direct co ntamination of these matrices by foliar sprays. Residues can in turn be brought back to bee colonies where in

- hive bees including young adult and developing brood (i.e., eggs, larvae and pupae) may be exposed. EPA guidance 1 on assessing the risk of pestic ides to bees identifies a suite of laboratory

- based studies intended that serve as the foundation for screening chemical for potential chronic effects to individual adult bees. The chronic oral toxicity study with adult bees provides 10

- day toxicity no

- ob served adverse effect level (NOAEL) and lowest

- observed adverse effect level (LOAEL) for assessing chronic effects to honey bees ( A. mellifera ) based on potential routes of chronic oral exposure.

Practical Utility of the Data How will the data be used? Data obtained from this study will be used in estimating chronic risk to individual adult bees. This is

a non

- guideline study; an OECD protocol is expected to be available in late 2014. A protocol should be submitted to the Agency for review before comme ncing the study and should include provisions for measuring the concentration of famoxadone in the actual diet of the honeybee.

How could the data impact the Agency’s future decision

- making? In the absence of these data, honey bee oral toxicity data for s urrogate pesticides

– starting with data for closely related pesticides and proceeding to data for less related pesticides

– may be used to characterize the chronic toxicity of famoxadone to honey bees. Risk estimates based on these data will be considered along with other lines of evidence to determine whether higher

- tier studies are needed at the whole colony level.

[1] USEPA. 1996. Residue Chemistry Test Guidelines OPPTS 860.1900 Field Accumulation in Rotational Crops. EPA 712

- C

- 96

- 189. file:///C:/Users/tsteeger/Downloads/EPA

- HQ

- OPPT

- 2009

- 0155

- 0019.pdf (last accessed 06/01/2104)

Study Title: Tier 1

- Larval Honeybee Acute and Chronic Oral Exposure Rationale for Requiring the Data Developing bee brood (i.e., larvae and pupae) can be exposed to pesticides through residues brought back to the colony by worker bees foraging in areas where the pesticide has been applied. While larvae are typically fed royal or brood jelly during their early stages of development, worker bee (females) and drone (males) larvae are also fed pollen/honey (bee bread) directly by in

- hive nurse bees. EPA guidance (USEPA 2014) on assessing the risk of pesticides to bees identifies a suite of laboratory

- based s tudies intended that serve as the foundation for screening chemical for potential acute and chronic effects to individual adult and larval bees.31 Practical Utility of the Data How will the data be used? The 21

- day larval toxicity study 1 under developmen t by OECD provides both acute and chronic toxicity data on developing bee brood and will yield a median lethal dose (LD50) for assessing acute toxicity during the early part of the study as well as a 21

- day no

- observed adverse effect level (NOAEL) and lowe st

- observed adverse effect level (LOAEL) for assessing chronic effects. Alternatively, registrants may submit a separate acute (single dose) larval toxicity study following OECD Guideline 237 2 as well as the 21

- day repeat dose chronic toxicity study to address both acute and chronic larval endpoints. Effects on survival and development (adult bee emergence) from repeat exposures to the active ingredient will be used in estimating chronic risk to individual brood. A protocol for the 21

- day larval toxicity test should be submitted to the Agency for review before commencing the study and should include provisions for measuring the concentration of famoxadone in the actual diet of the honeybee.

H ow could the data impact the Agency’s future decision

- making? Effects on survival and development from repeat exposures to the active ingredient will be used in estimating acute and chronic risk to individual brood. Risk estimates based on these data will be considered along with other lines of evidence to determine whether higher

- tier studies are needed at the whole colony level.

[1] Draft guidance for the 21

- day larval toxicity study is available at: http://www.oecd.org/env/ehs/testing/Draft_GD_honeybees_rep_exp_for_2nd_CR_25_November_2013.pdf
[ 2 ] OECD Guideline 237 is available at: http://www.oecd

ilibrary.org/docserver/download/9713171e.pdf?expires=1407449911&id=id&accname=guest&checksum=E67BEDEB01DB12D815E858CB45A9 89FB


### Study Title: Pollinator Tier II Semi

- Field Toxicity Testing (tunnel/enclosure studies) Rationale for Requiring the Data Tier II studies are conditional on the outcome of the screening

- level assessment where acute and/or chronic risk levels of concern have been exceeded for terrestrial invertebrates. Terrestrial invertebrates are likely to be impacted if exposed to pesticides in various use se ttings. Pesticide residues may be transferred to pollen and/or nectar of treated plants and subsequently brought back to the hive and may adversely affect developing brood (egg, larvae, and pupae) and adult bees

. Screening

- level (Tier I) studies of indiv idual bees do not address possible effects and/or exposure to pesticide residues at the colony

- level. Because of the potential for pollen and nectar to be contaminated with pesticide residues, and subsequently brought back to the hive, it is important to determine whether bee colonies may be negatively affected under relatively controlled exposure conditions of a semi

- field study. In addition to providing effects data, these studies can provide data on exposure as pesticide residues in pollen/nectar of tre ated plants.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for invertebrates with the honeybee. The guidance describes the tiered testing process and can be found at: http://www2.epa.gov/pollinator

- protection/pollinator

- risk

- assessment

- guidance

. Additional information on honeybee colony studies under semi

- field conditions can be found in the OECD Guidance 75 http://www.oecd.org/officialdocuments/publicdisplaydocumentpdf/?cote=env/jm/mono%28

. Practical Utility of the Data32

How will the data be used? Tier II colony

- level data will be used to assess potential risk to non

- target organisms including listed and non

- listed terrestrial social invertebrate species and to determine whether effects observed in the screening

- level (Tier I) laboratory

- based studi es of individual bees are evident in colony

- level studies under semi

- field conditions. The Tier II semi

- field test of whole colonies is a relatively controlled study, i.e ., bees are confined to a specific area, that is designed to represent potential fiel d

- level exposure and account for hive dynamics, which are not achievable from other pollinator studies. This study will be used to determine whether adverse effects to insect pollinators at the whole colony level, may result for the use of pesticides and will help to refine risk estimates derived in the screening

- level risk assessment for beneficial terrestrial invertebrates. Measured residues in pollen/nectar can also be used to refine risk estimates derived from model

- based or default values in the scre ening

- level assessment.

How could the data impact the Agency’s future decision

- making? The data will inform the determination required under FIFRA or the ESA as to whether continued registration of a pesticide is likely to result in unreasonable adverse e ffects to non

- target species or is likely to adversely affect federally listed threatened or endangered species or their designated critical habitat. Without these data, EPA may need to presume risk which will limit the flexibility of pesticide products t o comply with FIFRA and the ESA, and could result in significant use restrictions.

Study Title: Pollinator Tier II Semi

- Field Toxicit y Testing (feeding studies) Rationale for Requiring the Data Pesticide r esidues may be transferred to pollen and/or nectar of treated plants and subsequently brought back to the hiv e, and may adversely affect developing brood (egg
, larva e, and pupae ) and adult bees

. Tier II feeding studies are conditional on the outcome of the screening

- level assessment where acute and/ or chronic risk levels of concern have been exceeded for terrestrial invertebrates based on Tier I studies of individual bees. Feeding studies utilize free foraging bee colonies that are “dosed” with specific quantities of test material and represent a mea ns of ensuring exposure to the test material through spiked pollen and/or sugar solutions fed to the colony while still allowing the bees to forage freely. Since bee colonies are not confined to enclosures, colonies can be exposed for longer duration peri ods without subjecting the bees to stress that typically results from Tier II tunnel studies. Available toxicity studies of individual bees (Tier 1) conducted to support screening

- level
assessments do not address possible eff ects and/or exposure to pestic ide residues at the colony

level . Because of the potential for pollen and nectar to be contaminated with pesticide residues, and subsequently brought back to the hive, it is important to determine whether bee colonies may be negatively affected where bees are free foraging and have the option to collect/consume alternative forage items beyond the spiked food

. Since multiple dose levels can be more readily tested, feeding studies can help to define dose

- response relationships at the whole colony level.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for invertebrates with the honeybee. The guidance describes the tiered testing process and can be found at: http://www2.epa.gov/pollinator

- protection/pollinator

- risk

- assessment

- guidance

. Additional information on honeybee colony feeding studies can be found in the EPPO Guidance 170
at: http://www.nationalbeeunit.com/index.cfm?pageId=187

.33 Practical Utility of the Data How will the data be used? Tier II colony feeding data will be used to assess potential risk to non

- target organisms including listed and non

- listed terrestrial social invertebrate species. The colony feeding study is designed to represent potential field

- level exposure and account for hive dynamics using longer duration exposure periods than are possible in Tier II tunnel studies. The study will be used to determine whether potential adverse effects to insect pollinators at the whole colony level when bees are able to forage naturally beyond the spiked food. Results from the feeding study will help to refine the screening

- level risk a ssessment for beneficial terrestrial invertebrates that were based on Tier I studies on individual bees. Since feeding studies can help to define a dose

- response relationship at the colony level, the studies can provide a means of determining exposure thr esholds below which the likelihood of adverse effects on colonies may be low.

How could the data impact the Agency’s future decision

- making? Tier II colony

- level data will be used to refine screening

- level risk estimates derived using Tier I laboratory

- b ased data on individual bees. The Tier II data will inform the determination required under FIFRA or the ESA as to whether continued registration of a pesticide is likely to result in unreasonable adverse effects to non

- target species or is l ikely to adve rsely affect federally listed threatened or endangered species or their designated critical habitat. Without these data, EPA may need to presume risk which will limit the flexibility of pesticide products to comply with FIFRA and the ESA
, and could result in significant use restrictions.

Study Title: Tier II Nectar and Pollen Residue Study for Insect Pollinators Rationale for Requiring the Data Bees can be exposed to pesticides through multiple pathways including direct contact with sprays and dusts and through ingestion of residues in food/water (e.g., pollen/nectar and water used to maintain colony temperature). Worker bees foraging on flowers for pollen and nectar can be exposed to residues in pollen and nectar that i s translocated from ground application

. Famoxadone may be translocated to flowers and nectar. These r esidues can in turn be brought back to bee colonies where in

- hive bees including young adult and developing brood (i.e., eggs, larvae and
pupa e) may be exp osed. EPA guidance on assessing the risk of pesticides to bees identifies a tiered process where the initial screen is based on a suite of acute and chronic laboratory studies individual adult bees and larvae. If screening

- level assessment indicates poten tial chronic risks to in dividual bees, then higher

- tier studies may be required to examine potential routes of exposure at the colony level. Famoxadone is a fungicide that is applied pre and port

- emergence to control fungal pathogens on crops such as caneberries that rely on foraging insect pollinators, so there is a possibility of exposure to translocated residues in nectar and pollen. Practical Utility of the Data How will the data be used? Acute tests with adult bees have indicated that the active ingredient is moderately toxic to bees on
an acute contact exposure basis. If toxicity effects are observed in individual larval or adult bees from acute or chronic exposure
, nectar and pollen residue studies will determ ine if translocation is a possible route of exposure to insect pollinators and their colonies.34

How could the data impact the Agency’s future decision

- making? Exposure estimates based on these data will be considered along with other lines of evidence to

c haracterize the risk picture of famoxadone to foraging insect pollinators and whether Tier III studies are needed.

12. References

Andrieu, N., Jaworska, G., Genet, J.L., Bompeix, G. 2001. Biological mode of action of Famoxadone on Plasmopara viticola and Phytophthora infestans . Crop Protection 20: 253

- 260.

Brown, M.R. , 1998. Static

- Renewal, Acute, 48

- Hour Limit Test of IN

- JL856

- 1 to Daphnia magna . E. I. du Pont de Nemours and Company HLR 382

- 96 (9 May, 96), unpublished

.
Brown, M.R. , 1998. Flow

- Thr ough, Acute, 48

- Hour Limit Test of IN

- MN468

- 0 to Daphnia magna . E. I. du Pont de Nemours and Company HLR 848

- 96 (9 May, 96), unpublished

.
Brown, M.R. , 1998. Static, Acute, 48

- Hour Limit Test of IN

- H3310 2 to Daphnia magna E. I. du Pont de Nemours and Company HLR 380

- 96 (5 Sep, 96), unpublished

.
Brown, M.R. , 1998. Static, Acute, 48

- Hour Limit Test of IN

- JS940 1 to Daphnia magna . E. I. du Pont de Nemours and Company HLR 381

- 96 (22 Jul, 96), unpublished

.
Brown, M.R. , 1998. Acute Limit Toxicity Test with KF015 and the Daphnid, Daphnia magna . T.R. Wilbury Laboratories, Inc. E. I. du Pont de Nemours and Company AMR 3978

- 96 (9 Sep, 96), unpublished

USEPA. 2003. Famoxadone

- Health Effects Division (HED) Metabolism Assessment Re view Committee (MARC) Decision Document. DP Barcode D288134.

USEPA. 2008. Tier II Drinking Water Exposure Assessment for Famoxadone Use on Leafy Greens subgroup 4A, Bulb Vegetables Group 3, Cilantro and Caneberry subgroup 13A and Leaf Petioles subgroup 4 B . April 30, 2008. ( D347671, D347674).

USEPA. 2014a. Famoxadone (113202) EFED label data report, BEAD 10/17/2014.

USEPA. 2014 b . Famoxadone (113202): Screening Level Usage Analysis (SLUA). Biological and Economic Analysis Division, Office of Pesticide Programs. June 17, 2014.

USEPA. 2014c. Famoxadone (113202): BEAD Chemical Profile for Registration Review: Famoxadone (113202).

USEPA. 2014d. Screening level Usage Analysis (SLUA), June 2014.35 Appendix A. Chemical Identity of Famoxadone and Its Degradation Products Code Name/ Synonym Chemical Name Chemical Structure Study Type MRID Maximum %AR (day) Final %AR (study

length)

PARENT
Famoxadone (DPX

- JE874) CAS Name: 3

- anilo

- 5

-

methyl

- 5

- (4

- phenoxyphenyl)

- 1,3

- oxazolidine

- 2,4

- dione

CAS Number:

Formula

MW:

Smiles CC1(C(=O)N(C(=O)O1)NC2= CC=CC=C2)C3=CC=C(C=C3)O C4=CC=CC=C4 Hydrolysis pH 4 at 25oC

44946336 52.3 (30 days)
Hydrolysis pH 7 at 25oC 18 (5 days)
Hydrolysis pH 9 at 25oC 8.3 (5 hours)
Photolysis 44946338 5.7 (15 days)
Aerobic Aquatic Metabolism 44946405 0.4 (30 days)

Anaerobic Soil Metabolism 44946404 4.8 (120 days)

Aerobic Soil Metabolism 44946402 11.2 (174 days)

Aerobic Soil Metabolism 44946339 4.2 (118 days)

DEGRADATES

IN

- KZ007 CAS Name: 5

- [4

- (4

-

hydroxyphenoxy)phenyl]

- 5

- methyl

- 3

- (phenylamino)

- 2,4

- oxazolidinedione

CAS Number:

Formula

MW: Aerobic Aquatic Met. Water 44946405 5.5 (4 days) 0.1 (21 days)

Aerobic Aquatic Met. Sediment 44946405 5.7 (7 days) 3.4 (21 days)

Anaerobic Soil Metabolism 44946404 3.7 (0 days) 1.1 (120 days)

Aerobic Soil Metabolism 44946402 6.3 (4 days) 0.3 (174 days)36 Code Name/ Synonym Chemical Name Chemical Structure Study Type MRID Maximum %AR (day) Final %AR (study

length)
Smiles: CC1(C(=O)N(C(=O)O1)Nc2cc ccc2)c3ccc(cc3)Oc4ccc(cc4) O Aerobic Soil Metabolism 44946339 16.2 (4 days) 9.8 (118 days)

IN

- MN467 CAS Name: 5

- methyl

- 3

- [(2

-

nitrophenyl)amino]

- 5

- (4

- phenoxyphenyl)

- 2,4

- oxazolidinedione

CAS Number:

Formula

MW:

Smiles: CC1(C(=O)N(C(=O)O1)Nc2cc ccc2[N+](=O)[O

- ])c3ccc(cc3)Oc4ccccc4 Photolysis 44946338 18.3 (7 days) 10.2 (15 days)

Aerobic Soil Metabolism 44946402 1.7 (174 days) 1.7 (174 days)

Aerobic Soil Metabolism 44946339 8.8 (30 days) 3.1 (118 days)

IN

- MN468 CAS Name: (5

- methyl

- 3

- [(4

-

nitrophenyl)amino]

- 5

- (4

- phenoxyphenyl)

- 2,4

- oxazolidinedione)

CAS Number:

Formula

MW: Photolysis 44946338 13.4 (15 days) 13.4 (15 days)37 Code Name/ Synonym Chemical Name Chemical Structure Study Type MRID Maximum %AR (day) Final %AR (study

length)
Smiles: CC1(C(=O)N(C(=O)O1)Nc2cc c(cc2)[N+](=O)[O

- ])c3ccc(cc3)Oc4ccccc4

IN

- JL856 CAS Name: α

- hydroxy

- α

methyl

- 4

- phenoxybenzeneacetic acid

- 2

- phenylhydrazide

CAS Number:

Formula

MW:

Smiles: CC(c1ccc(cc1)Oc2ccccc2)(C( =O)NNc3ccccc3)O Hydrolysis pH 4 at 25oC 44946336 5.0 (30 days) 5.0 (30 days)
Hydrolysis pH 7 at 25oC 14.1 (5 days) 14.1 (5 days)
Hydrolysis pH 9 at 25oC 20.4 (5 hours) 20.4 (5 hours)
Aerobic Aquatic Met. Water 44946405 5.5 (4 days) 0.1 (21 days)

Aerobic Aquatic Met. Sediment 44946405 5.5 (4 days) 3.1 (21 days)

Photolysis pH 5 44946337 11.0 (6 days) 11 (6 days)

IN

- KF015 CAS Name: 5

- methyl

- 5

- (4

-

phenoxyphenyl)

- 2,4

- oxazolidinedione)

CAS Number:

Formula

MW:

Smiles: CC1(C(=O)NC(=O)O1)c2ccc( cc2)Oc3ccccc3 Photolysis 44946338 21.5 (1 day) 6.3 (15 days)
Photolysis pH 5 44946337 11.0 (6 days) 11.0 (6 days)38 Code Name/ Synonym Chemical Name Chemical Structure Study Type MRID Maximum %AR (day) Final %AR (study

length)
IN

- JS940 CAS Name: (α

- hydroxy

- α

methyl

- 4

- phenoxybenzeneacetic acid)

CAS Number:

Formula

MW:

Smiles: CC(c1ccc(cc1)Oc2ccccc2)(C( =O)O)O Hydrolysis pH 4 at 25oC 44946336 30.5 (30 days) 30.5 (30 days)
Hydrolysis pH 7 at 25oC 51.7 (5 days) 51.7 (5 days)
Hydrolysis pH 9 at 25oC 19.8 (5 hours) 19.8 (5 hours)
Soil Photolysis 44946338 6.9 (15 days) 6.9 (15 days)
Aerobic Aquatic Met. Water 44946405 20.5 (3 days) 0.5 (21 days)

Aerobic Aquatic Met. Sediment 44946405 6.5 (2 days) 2.7 (21 days)

Soil Photolysis pH 5 44946337 21.7 (6 days) 21.7 (6 days)

Anaerobic Soil Metabolism 44946404 13.9 (91 days) 9.6 (120 days)

Aerobic Soil Metabolism 44946402 3.7 (6 days) 0.5 (174 days)

mAerobic Soil Metabolism 44946339 4.7 (30 days) 3.1 (118 days)

IN

- H3310 CAS Name: (1

- (4

-

phenoxyphenyl)ethanone)

CAS Number:

Formula

MW: Hydrolysis pH 4 at 25oC 44946336 2.9 (30 days) 2.9 (30 days)
Hydrolysis pH 7 at 25oC 11.9 (2 days) 11.7 (5 days)
Hydrolysis pH 9 at 25oC 0.6 (5 hours) 0.6 (5 hours)
Soil Photolysis 44946338 26.6 (10 days) 21.9 (15 days)
Aerobic Aquatic Met. Water 44946405 2.4 (0.25 days) 0.1 (21 days)39 Code Name/ Synonym Chemical Name Chemical Structure Study Type MRID Maximum %AR (day) Final %AR (study

length)
Smiles: CC(=O)c1ccc(cc1)Oc2ccccc2 Aerobic Aquatic Met. Sediment 44946405 10.7 (7 days) 2.8 (21 days)

Soil Photolysis pH 5 44946337 39.3 (6 days) 39.3 (6 days)

Anaerobic Soil Metabolism 44946404 3.4 (91 days) 1.9 (120 days)

IN

- MN968 CAS Name:

CAS Number:

Formula

MW:

Smiles: Hydrolysis pH 4 at 25oC 44946336 0 0
Hydrolysis pH 7 at 25oC 0 0
Hydrolysis pH 9 at 25oC 39.3 (4 hours) 38.1 (5 hours)40

Appendix B : A Summary of the Registered Uses of Famoxadone Use Product Name Reg No Method of Application Maximum

Single Application Rate ( lb famoxadone /A) (min application interval) Max A nnual

Application Rate (lb famoxadone /A)

Bulb Vegetables Tanos 1 352

- 604 Ground broadcast, aerial broadcast, Chemigation 8 apps at

0.156 (5 days) 2 1.3125

Bulb Onion (subgroup 3

- 07 A): Tanos 352

- 604 Ground broadcast, aerial broadcast, Chemigation 8 apps at

0.156 (5 days) 3 1.3125

C aneberries, (subgroup 13

- 07 A) Tanos 352

- 604 Ground broadcast, aerial broadcast, Chemigation 7 apps at

0.156 (5 days) 1.125

Cucurbit Vegetables: Cantaloupe, Cucumber, Honeydew Melon, Muskmelon, Watermelon, Pumpkin, Summer Squash, Winter Squash, and other Cucurbits Tanos 352

- 604 Ground broadcast,

aer ial broadcast, Chemigation 9 apps at

0.125 (5 days) 4 1.125

Grapes* (East of the Rocky Mountains) Tanos 352

- 604 Ground broadcast, aerial 9 apps at

0.125 (10 days) 1.12541 broadcast, Chemigation

Hops Tanos 352

- 604 Ground broadcast, aerial broadcast, Chemigation 6 apps at

0.125 (6 days) 0.75

Leafy Vegetables (except Brassica), group 4: Leafy greens subgroup 4A: Tanos 352

- 604 Ground broadcast, aerial broadcast, Chemigation Maximum

annual number of applications 8 apps at 0.156 (5

- days) 1.248

Spinach; Spinach, New Zealand; Spinach, vine Tanos 352

- 604 Ground broadcast, aerial broadcast, Chemigation Number of

applications
per cropping cycle (year)

- 8 apps at 0.156 (5 days) 2 1.3125

Peppers ( a ll varieties of peppers) including: pimentos and bell, hot, and sweet peppers Tanos 352

- 604 Ground broadcast, aerial broadcast, Chemigation 7 apps at

0.156 (5 days) 1.125

Potatoes Tanos 352

- 604 Ground broadcast, aerial broadcast, Chemigation 9 apps at

0.125 (7 days) 1.125

Tomatoes Tanos 352

- 604 Ground broadcast,

aer ial broadcast, Chemigation 9 apps at

0.125 (5 days) 1.125

Fungicide manufacturing Famoxadone

Technical 352

- 605 N/A X N/A N/A

1 Product is not registered in CA (for any uses)

2 Communication with the registrant is currently ongoing with regard to the maximum number of annual applications of famoxadone to spinach. The label currently lists the number of applications in terms of cropping cycles, and there may be more than one cropp ing cycle per season for these crops depending on the geographic region.42

Appendix C: Previous Actions and Assessed Uses for Famoxadone Use Site Max. Application Rate

(lb ai/A) Number of applications (Application Interval in Days) Action/DP Barcode/Date

Single (App Method) Seasonal/

Annual

Leafy Greens (subgroup 4a)

Bulb Veg. (group 3), Cilantro

Cranberry (subgroup 13a)

Leafy Petioles (subgroup 4b) 0.156 (F)

0.156 (F)

0.156 (F)

0.156 (F) 0.75

1.3125

1.125

0.75 4 (NS)*

8 (NS)*

8 (NS)*

4 (NS)* Section 3

- New Use

D349252 6/30/2008

Leafy Greens (subgroup 4a)

Bulb Veg. (group 3), Cilantro

Caneberry (subgroup 13a)

Leafy Petioles (subgroup 4b) 0.156 (F)

0.156 (F)

0.156 (F)

0.156 (F) 0.75

1.3125

1.125

0.75 4 (NS)*

8 (NS)*

8 (NS)*

4 (NS)* Tier II DWA

D347671, D347674 4/30/2008

Grapes,

Hops,

Caneberries 0.125

0.156

0.1875 0.375

0.468

1.125 per crop cycle 3

3

6 (5

- 7) Section 3

- New Use

D331970 12/29/2006

Grapes,

Hops,

Caneberries 0.125

0.156

0.1875 0.375

0.468

1.125 per crop cycle 3

3

6 (5

- 7) Tier II DWA

D323683, D331970 12/6/2006

Soybean 0.05

- 0.065 (A,

G) 0.13 2 (14

- 21) Section 18

- Emergency Exemption Minnesota, S. Dakota D319075 12/12/2005 Soybean 0.05

- 0.065 (A, 0.13 2 (14

- 21) Section 18

- Emergency43 G) Exemption DWA Minnesota, S. Dakota D321060 8/31/2005 Cucurbits Head Lettuce Potatoes Fruiting Veg. 0.1875 (A) 1.125 6 (5) Section 3

- New Uses D276071, D285923 3/25/2003

Potatoes, Fruiting Vegetables, Curcurbit Vegetables, Head Lettuce 0.1875 1.125 6 (5) Tier II DWA D286872 1/10/2003

Potatoes, Fruiting Vegetables, Curcurbit Vegetables, Head Lettuce 0.1875 1.125 6 (5) Tier II DWA D286872 12/13/2002

*Value is assumed. N/A= Not applicable, NS = Not specified, DWA = Drinking Water Assessment G = ground, A = aerial44

Appendix D: Inputs and Outputs from SIP Program

Table 1. Inputs Parameter Value Chemical name Solubility (in water at 25 o C; mg/L) 0.52

Mammalian LD 50 (mg/kg

- bw) 5000 Mammalian test species laboratory rat Body weight (g) of "other" mammalian species

Mammalian NOAEL (mg/kg

- bw) 200 Mammalian test species laboratory rat Body weight (g) of "other" mammalian species

Avian LD 50 (mg/kg

- bw) 2250 Avian test species northern bobwhite quail Body weight (g) of "other" avian species Mineau scaling factor 1.15

Mallard NOAEC (mg/kg

- diet) 5620 Bobwhite quail NOAEC (mg/kg

- diet) 2250 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 Parameter Acute Chronic Upper bound exposure (mg/kg

- bw) 0.0894 0.0894 Adjusted toxicity value (mg/kg

- bw) 3845.8028 153.8321 Ratio of exposure to toxicity 0.0000 0.0006

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) 0.4212 0.4212 Adjusted toxicity value (mg/kg

- bw) 1620.9664 239.1712 Ratio of exposure to acute toxicity 0.0003 0.0018

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.45

Appendix E: Inputs and Outputs from STIR Program 

## Input

Application and Chemical Information Enter Chemical Name Famoxadone Enter Chemical Use Fungicide 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) 374.4 Enter Chemical Vapor Pressure (mmHg) 4.80E

- 09 Enter Application Rate (lb a.i./acre) 1.35

Toxicity Properties
Bird Enter Lowest Bird Oral LD 50 (mg/kg bw) 2250 Enter Mineau Scaling Factor 1.15 Enter Tested Bird Weight (kg) 0.178 Mammal Enter Lowest Rat Oral LD 50 (mg/kg bw) 5000 Enter Lowest Rat Inhalation LC 50 (mg/L) 5.3 Duration of Rat Inhalation Study (hrs) 4 Enter Rat Weight (kg) 200 

## Output Results Avian (0.020 kg ) Maximum Vapor Concentration in Air at Saturation (mg/m 3 ) 9.67E

- 05 Maximum 1

- hour Vapor Inhalation Dose (mg/kg) 1.22E

- 05 Adjusted Inhalation LD 50 2.33E

- 02 Ratio of Vapor Dose to Adjusted Inhalation LD 50 5.22E

- 04 Exposure not Likely Significant Maximum Post

- treatment Spray Inhalation Dose (mg/kg) 1.43E

- 01 Ratio of Droplet Inhalation Dose to Adjusted Inhalation LD 50 6.13E+00 Proceed to Refinements


### Results Mammalian (0.015 kg ) Maximum Vapor Concentration in Air at Saturation (mg/m 3 ) 9.67E

- 05 Maximum 1

- hour Vapor Inhalation Dose (mg/kg) 1.53E

- 05 Adjusted Inhalation LD 50 2.70E+00 Ratio of Vapor Dose to Adjusted Inhalation LD 50 5.66E

- 06 Exposure not Likely Significant Maximum Post

- treatment Spray Inhalation Dose (mg/kg) 1.79E

- 01 Ratio of Droplet Inhalation Dose to Adjusted Inhalation LD 50 6.64E

- 02 Exposure not Likely Significant46

Appendix F : Bibliography

Environmental Fate (sorted by MRID)

MRID Citation Reference

44946336 Jernberg , K.; Lee, D. (1996) Hydrolysis of (14

- carbon) DPX

- JE874 in Buffer Solutions of pH 5, 7, and 9: Lab Project Number: AMR 2433

- 92. Unpublished study prepared by E.I. du Pont de Nemours and Company. 84 p.

44946337 Jernberg, K.; Lee, D. (1996) Photolysis of ( 14

- carbon) DPX

- JE874 in Ph 5 Buffer Solution: Lab Project Number: AMR 2503

- 92. Unpublished study prepared by E.I. du Pont de Nemours and Company. 72 p.

44946338 Schneiders, G.; Irelan, M. (1996) Photodegradation of Radiolabeled DPX

- JE874 on Soil Conducted in Simulated Sunlight: Lab Project Number: AMR 3144

- 94. Unpublished study prepared by E.I. du Pont de Nemours and Company. 88 p.

44946339 Kaman, R. (1996) Degradation of (14

- carbon)DPX

- JE874 in Four Soils: Lab Project Number: 6626

- 95

- 0223

- EF

- 001: AMR 367 0

- 95. Unpublished study prepared by Ricerca, Inc. 114 p.

44946402 Kaman, R. (1996) Aerobic Soil Metabolism of (carbon

- 14)DPX

- JE874: Lab Project Number: 6496

- 95

- 0116

- EF

- 001: AMR

- 3556

- 95. Unpublished study prepared by Ricerca, Inc. 108 p.

44946403 Grochuls ka, J. (1999) Aerobic Soil Metabolism of (carbon

- 14)DPX

- JE874: Supplement No. 1: Lab Project Number: AMR 3556

- 95: 6496

- 95

- 0116

- EF

- 001. Unpublished study prepared by Ricerca, Inc. 12 p.

45294102 Hatzenbeler, C. (2000) Rate of Degradation Study of IN

- JS940 (a Metabolite of Famoxadone) in Three Soils: Lab Project Number: 4026: 012683

- 1. Unpublished study prepared by Ricerca, LLC. 48 p.

45358801 Theilacker, W.; Van

- Nguyen, A. (2000) Rates of Degradation of IN

- KZ007 (A Metabolite of Famoxadone) on Three Aerob ic Soils: Lab Project Number: DUPONT

- 4300: 4300. Unpublished study prepared by DuPont Agricultural Products. 39 p.

44946404 Hatzenbeler, C.; Kaman, R. (1996) Anaerobic Soil Metabolism of (carbon

14)DPX

- JE874: Lab Project Number: AMR 3579

- 95: 6506

- 95

- 0120

- EF

- 001. Unpublished study prepared by Ricerca, Inc. 104 p.

45294102 Hatzenbeler, C. (2000) Rate of Degradation Study of IN

- JS940 (a Metabolite of Famoxadone) in Three Soils: Lab Project Number: 4026: 012683

- 1. Unpublished study prepared by Ricerca, LLC. 4 8 p.47

44946401 Grochulska, J. (1999) Degradation of (carbon

- 14)DPX

- JE874 in Four Soils: Supplement No. 1: Lab Project Number: AMR 3670

- 95: 6496

- 95

- 0116

- EF

- 001. Unpublished study prepared by Ricerca, Inc. 17 p.

44946406 DeLisio, P.; McClanahan, R. (1996) A ged Soil Column Leaching Study of (carbon

14)DPX

- JE874: Lab Project Number: 6649

- 95

- 0228

- EF

- 001: AMR 3676

- 95. Unpublished study prepared by Ricerca, Inc. 54 p.

44946407 Jernberg, K. (1995) Soil Batch Equilibrium (Adsorption/Desorption) Study of DPX

- JE874: Lab Project Number: AMR 2741

- 93. Unpublished study prepared by DuPont Agricultural Products. 31 p.

44946408 2012555 Ball, M. (1999) Soil Batch Equilibrium (Adsorption/Desorption) Study of DPX

- JE874: Supplement No. 1: Lab Project Number: AMR 2741

- 93. Unpu blished study prepared by DuPont Agricultural Products. 8 p.

44946409 Rose, K. (1996) Environmental Fate Studies of IN

- KF015, a Degradation Product of DPX

- JE874: Rate of Degradation in Soil and Adsorption to Soil: Lab Project Number: 6829

- 96

- 0050

- EF

- 001: AMR 3937

- 96. Unpublished study prepared by Ricerca, Inc. 37 p.

45294103 Singles, S. (2000) Adsorption/Desorption of IN

- JS940 (a Metabolite of Famoxadone) in Four Soils: Lab Project Number: 3834. Unpublished study prepared by E.I. du Pont de Nemours and Co mpany. 70 p.

45294104 Ohm, M.; Theilacker, W. (2000) Adsorption/Desorption of Famoxadone Metabolite IN

- KZ007: Lab Project Number: 3266. Unpublished study prepared by E.I. du Pont de Nemours and Company. 50 p.

46350401 Hahn, J. (2004) Batch Equilibrium (A dsorption/Desorption) of DPX

- JE874 (Famoxadone) in One Soil. Project Number: 48786, 13880. Unpublished study prepared by ABC Laboratories. 42 p.

44946410 McClory, J.; Holt, J. (1999) Field Soil Dissipation of Famoxadone and Cymoxanil Following Application of DPX

- KP481 Fungicide, USA: Lab Project Number: ML97

- 0705DUP: AMR 4329

- 97. Unpublished study prepared by DuPont Agricultural Products and Morse Laboratories, Inc. 214 p.

45294105 McClory, J. (2000) Field Soil Dissipation of Famoxadone and Cymoxanil Follo wing Application of DPX

- KP481 50WG Fungicide, WG, USA, 1999: Lab Project Number: 2342: ML99

- 0780

- DUP. Unpublished study prepared by E.I. du Pont de Nemours and Company and Morse Laboratories. 221 p.

45294106 McClory, J. (2000) Field Soil Dissipation of Fa moxadone and Cymoxanil Following Application of DPX

- KP481 50WG Fungicide, WG, USA, 1999: Lab Project Number: AMR 4329

- 97: ML97

- 0705

- DUP. Unpublished study prepared by E.I. du Pont de Nemours and Company and Morse Laboratories. 205 p.

45358802 Bechtel, D. (2000) Field Soil Dissipation of Famoxadone and Indoxacarb Following Separate of Tank Mix Applications of DPX

- KP481 Experimental Fungicide and Avaunt Insecticide at Two Canadian Sites: Lab Project Number:48 AMR 5119

- 98: ML98

- 0740

- DUP: JEMP

- 98

- 920. Unpublishe d study prepared by Morse Labs., Inc. University of Guelph. 225 p.

44946405 Hatzenbeler, C. (1996) Degradation of (carbon

- 14)DPX

- JE874 in the Water/Sediment System: Lab Project Number: 6636

- 95

- 0230

- EF

- 001: AMR 3662

- 95. Unpublished study prepared by Ricerc a, Inc. 89 p.

44946413 Kreamer, G. (1996) Bioconcentration of (Carbon

- 14)DPX

- JE874 in Bluegill Sunfish, Lepomis macrochirus: Lab Project Number: 670

- 94: 9826: AMR 2493

- 92. Unpublished study prepared by E.I. du Pont de Nemours and Company. 85
p.

44946414 Grochulska, J. (1999) Predicted Environmental Concentrations of Famoxadone in Surface Water, Groundwater and Soil Resulting from Application of DPX

KP481 to Potatoes, Tomatoes, Curcurbits, and Lettuce for USA: Lab Project Number: DUPONT

- 1733. Unpublished s tudy prepared by E.I. du Pont de Nemours and Company. 43 p.

44946335 Ball, M. (1999) Comprehensive Evaluation of the Environmental Fate of Famoxadone Fungicide: Lab Project Number: DUPONT

- 2161. Unpublished study prepared by E.I. du Pont de Nemours and Com pany. 45 p.

47242527 Jernberg, K.; Class, T.; Hausmann, S. (2000) Freezer Storage Stability of Famoxadone and Flusilazone in Oil Seeds (Oilseed Rape). Project Number: AMR/5132/98, 274/G. Unpublished study prepared by PTRL Europe Gmbh. 56
p.

44967204 Validation of Two Analytical Methods For The Determination Of Famoxadone In Water By GC/ECD". ECM0199W1

Environmental Effects

44946232 Campbell, S.; Beavers, J. (1994) DPX

- JE874

- 221: An Acute Oral Toxicity Study

with the Northern Bobwhite: Lab Projec t Number: 112

- 372: 404

- 94: 9819

- 002. Unpublished study prepared by Wildlife International Ltd. 27 p.

44946318 Palmer, S.; Grimes, J.; Beavers, J. (1996) DPX

- KX007

- 5: An Acute Oral Toxicity

Study with the Northern Bobwhite: Lab Project Number: 112

- 443: 4 103

- 96. Unpublished study prepared by Wildlife International Ltd. 43 p.

44946233 Campbell, S.; Beavers, J. (1994) DPX

- JE874

- 221: A Dietary LC50 Study with the Northern Bobwhite: Lab Project Number: 112

- 370: 437

- 94: 9819

- 002. Unpublished study prepared by Wildlife International Ltd. 34 p.

44946234 Campbell, S.; Beavers, J. (1994) DPX

- JE874

- 221: A Dietary LC50 Study with the Mallard: Lab Project Number: 409

- 94: 9819

- 002: 112

- 371. Unpublished study prepared by Wildlife International Ltd. 34 p.

44946235 Fosters, J.; Beavers, J.; Jaber , M. et al. (1996) DPX

- JE874

- 221: A Reproduction Study with the Northern Bobwhite (Colinus virginianus): Lab Project Number:49 112

- 386: 744

- 95. Unpublished study prepared by Wildlife International Ltd. 171 p.

44946236 Fosters, J.; Beavers, J.; Jaber, M. e t al. (1998) DPX

- JE874

- 221: A Reproduction Study with the Northern Bobwhite (Colinus virginianus): Supplemental No. 1: Lab Project Number: 744

- 95: 112

- 386. Unpublished study prepared by Wildlife International Ltd. 8 p.

44946237 Fosters, J.; Beavers, J.; Jaber, M. et al. (1996) DPX

- JE874

- 221: A Reproduction Study with the Mallard (Anas platyrhynchos): Lab Project Number: 745

- 95: 112

- 387. Unpublished study prepared by Wildlife International Ltd. 173 p.

44946238 Fosters, J.; Beavers, J.; Jaber, M. et al. (1996) DPX

- JE874

- 221: A Reproduction Study with the Mallard (Anas platyrhynchos): Supplement No. 1: Lab Project Number: 745

- 95: 112

- 387. Unpublished study prepared by Wildlife International Ltd. 8 p.

44967202 Grove, A. (1996) Extended Laboratory Study Comparing the Effects of DPX

KX007 (Containing DPX

- JE874 and Cymoxanil) WG and SC Formulations on Typhlodromus pyri, Following Multiple Applications on Grapevine Leaves Under Greenhouse Conditions: Lab Project Number: AMR 3312

- 96: DU003TPS. Unpublished stu dy prepared by Mitox Stichting Duurzame Plaagbestrijding. 38 p.

44946239 Brown, M. (1994) Flow

- Through Acute, 96

- Hour LC50 of DPX

- JE874

- 133 to Rainbow Trout, Oncorhynchus mykiss: Revision No. 2: Lab Project Number: 9581

- 046: 518

- 93. Unpublished study prepared by E.I. du Pont de Nemours and Co. 37 p.

44946301 Brown, M. (1994) Flow

- Through Acute, 96

- Hour LC50 of DPX

- JE874

- 133 to Bluegill Sunfish, Lepomis macrochirus: Revision No. 2: Lab Project Number: 9581

- 046: HLR 661

- 93: HA

- 93

- 032. Unpublished study prepared by E.I. du Pont de Nemours and Company. 38 p.

44946302 Samel, A. (1999) DPX

- KX007: Static, Acute, Toxicity to Rainbow Trout, Oncorhynchus mykiss, in the Presence of Sediment: Lab Project Number: HL

1998

- 01530. Unpublished study prepared by E.I. du Pont de Nemours and Company. 37 p.

44946303 Samel, A. (1998) DPX

- KP48 1: Static, Acute, Toxicity to Rainbow Trout, Oncorhynchus mykiss, in the Presence of Sediment: Lab Project Number: DUPONT

- 1296. Unpublished study prepared by E.I. du Pont de Nemours and Company. 38 p.

46144801 Brown, M. (1997) DPX

- KP481

- 25 50WG: Flow

- Th rough, Acute, 96

- Hour LC50 to Rainbow Trout, Oncorynchus mykiss. Project Number: 10403, HL/1997/00440. Unpublished study prepared by Dupont Haskell Laboratory. 39 p.

44946306 Brown, M. (1997) IN

- JS940

- 1: Static, Acute, 96

- Hour Limit Test to Rainbow Trout, Oncorhynchus mykiss: Lab Project Number: 636

- 96: 10589.50 Unpublished study prepared by E.I. du Pont de Nemours and Company. 29 p. Metabolite of Famoxadone

44946307 Boeri , R.; Kowalski, P.; Ward, T. (1994) Flow

- Through, Acute 48

- Hour EC50 of DPX

- JE874

- 133 to Daphnia magna: Lab Project Number: 748

- 93: 255

- DU: HA

93

- 113. Unpublished study prepared by E.I. du Pont de Nemours and Company. 126 p.

44946305 Brown, M. (1996) St atic, Acute, 48

- Hour Limit Test of IN

- JS940

- 1 to Daphnia magna: Lab Project Number: HLR381

- 96: 10589. Unpublished study prepared by E.I. du Pont de Nemours and Company. 27 p. PC Code 613202 Benzeneacetic acid,.alpha.

- hydroxy

- .alpha.

- methyl

- 4

- phenoxy

4494 6309 Ward, T.; Kowalski, P.; Boeri, R. (1997) Flow

- Through Acute Toxicity of DPX

JE874

- 221 to the Sheepshead Minnow, Cyprinodon variegatus: Lab Project Number: HLO

- 1997

- 00166: 10370: 796

- DU. Unpublished study prepared by T.R. Wilbury Laboratories, Inc. 41 p.

44946310 Boeri, R.; Magazu, J.; Ward, T. (1998) Famoxadone Technical: Flow

- Through Mollusc Shell Deposition Test: Lab Project Number: AMR 4642

- 97: 1341

- DU. Unpublished study prepared by T.R. Wilbury Laboratories, Inc. 39 p.

44946311 Ward, T.; Kowalski, P.; Boeri, R. (1997) Acute Toxicity of DPX

- JE874

- 221 to the Mysid, Mysidopsis bahia: Lab Project Number: HLO1077

- 96: 10370: 797

- DU. Unpublished study prepared by T.R. Wilbury Laboratories, Inc. 40 p.

44946308 Forster, A. (1999) (Carb on

- 14) Famoxadone: To Assess the Toxicity to the Sediment Dwelling Phase of the Midge Chironomus riparius: Lab Project Number: 1538: DPT461: DUPONT1154. Unpublished study prepared by Huntingdon Life Sciences Ltd. 73 p.

44946312 Kreamer, G. (1996) Early Life

- Stage Toxicity of DPX

- JE874

- 221 with Rainbow Trout, Oncorhynchus mykiss: Lab Project Number: HLR300

- 95: 10025

- 001: MR10025. Unpublished study prepared by E.I. du Pont de Nemours and Company. 616 p.

44946313 Brown, M. (1996) Flow

- Through, 21

- Day Tox icity of DPX

- JE874

- 221 to Daphnia magna: Lab Project Number: HLR90

- 95: 9819

- 001: HA

- 94

- 106. Unpublished study prepared by E.I. du Pont de Nemours and Company. 377
p.

44946314 Boeri, R.; Magazu, J.; Ward, T. (1998) Famoxadone Technical: Flow

- Through Earl y Life Stage Toxicity to the Sheepshead Minnow, Cyprinodon variegatus: Lab Project Number: AMR 4644

- 97: 1343

- DU. Unpublished study prepared by T.R. Wilbury Laboratories, Inc. 50 p.

44946315 Ward, T.; Magazu, J.; Boeri , R. (1998) Famoxadone Technical: Flow

- Through Chronic Toxicity to the Mysid, Mysidopsis bahia: Lab Project Number: AMR 4643

- 97: 1342

- DU. Unpublished study prepared by T.R. Wilbury Laboratories, Inc. 58 p.51

44946319 Heldreth, K. (1998) DPX

- JE874: Influen ce on Seedling Emergence and Vegetative Vigor of Several Terrestrial Plants: Lab Project Number: AMR 4964

- 98: MR12199. Unpublished study prepared by E.I. du Pont de Nemours and Company. 105 p.

44946320 Sloman, T.; Leva, S. (1998) Famoxadone Technical: I nfluence on Growth and Reproduction of Lemna gibba G3: Lab Project Number: AMR 3601

- 95: MR11687: HA

- 97

- 144. Unpublished study prepared by E.I. du Pont de Nemours and Company. 36 p.

44946321 Boeri, R.; Magazu, J.; Ward, T. (1997) Famoxadone Technical: Gr owth and Reproduction Test with the Marine Alga, Skeletonema costatum: Lab Project Number: AMR 4647

- 97: 1346

- DU. Unpublished study prepared by T.R. Wilbury Laboratories, Inc. 39 p.

44946322 Thompson, S. (1996) DPX

- JE874

- 221: Influence on Growth and Repr oduction of Selenastrum capricornutum: Lab Project Number: 112A

- 139: AMR 3422

- 95. Unpublished study prepared by Wildlife International Ltd. and E.I. du Pont de Nemours and Company. 47 p.

44946323 Boeri, R.; Magazu , J.; Ward, T. (1998) Famoxadone Technical: Growth and Reproduction Test with the Freshwater Alga, Navicula pelliculosa: Lab Project Number: AMR 4645

- 97: 1344

- DU. Unpublished study prepared by T.R. Wilbury Laboratories, Inc. 41 p.

44946324 Boeri, R.; Ma gazu, J.; Ward, T. (1998) Famoxadone Technical: Growth and Reproduction Test with the Freshwater Alga, Anabaena flos

- aquae: Lab Project Number: AMR4646

- 97: 1345

- DU. Unpublished study prepared by T.R. Wilbury Laboratories, Inc. 40 p.

44946325 Palmer, S.; Beavers, J. (1994) DPX

- JE874

- 133: A Dietary LC50 Toxicity Study with the Honey Bee: Final Report: Lab Project Number: 112

- 358: 278

- 94. Unpublished study prepared by Wildlife International Ltd. 15 p.

44946326 Palmer, S.; Beavers, J. (1994) DPX

- JE874

- 133: An Acute Contact Toxicity Study with the Honey Bee: Final Report: Lab Project Number: 112

- 359: 279

- 94: 9700

- 001. Unpublished study prepared by Wildlife International Ltd. 16 p.

46350402 Priester, T. (1996) D PX

- KX007

- 5: Laboratory Acute Oral and Contact Toxicity Test with the Honeybee, Apis mellifera: Final Report. Project Number: 96/005/1028, 1028/001/265, AMR/3828/96. Unpublished study prepared by Springborn Laboratories (Europe) Ag. 40 p.

46350403 Sinderm ann, A.; Porch, J.; Krueger, H. (2004) Cymoxanil/Famoxadone (DPX

KP481) 50WG (1:1): A Foliage Residue Toxicity Study with the Honey Bee. Project Number: 112/550, DUPONT/14096, 15296. Unpublished study prepared by Wildlife International, Ltd. 25 p.

4494632 5 Palmer, S.; Beavers, J. (1994) DPX

- JE874

- 133: A Dietary LC50 Toxicity Study with the Honey Bee: Final Report: Lab Project Number: 112

- 358: 278

- 94. Unpublished study prepared by Wildlife International Ltd. 15 p.52

44946327 Kuhner, C. (1997) DPX

- KP481, a Water Dispersible Granular (WG) Formulation Containing DPX

- JE874 (254 g ai/kg) and Cymoxanil (266 g ai/kg): Acute Toxicity to the Staphylinid Beetle, Aleochara bilineata Gyll. (Coleoptera, Staphylinidae) in the Laboratory: Final Report: Lab Project Number : AMR 4235

- 96: 96259/01

- NLAB. Unpublished study prepared by GAB Biotechnologie GmbH and IFU Umweltanalytik GmbH. 22 p.

44946328 Kuhner, C. (1997) DPX

- KP481, a Water Dispersible Granular (WG) Formulation Containing DPX

- JE874 (254 g ai /kg) and Cymoxanil (266 g ai/kg): Acute Toxicity to the Green Lacewing, Chrysoperla carnea steph. (Neuroptera, Chrysopidae) in the Laboratory: Final Report: Lab Project Number: AMR4234

- 96: 96259/01

- NLCC. Unpublished study prepared by GAB Biotechnologie Gmb H IFU Umweltanalytik GmbH. 25 p.

44946329 Kuhner, C. (1997) DPX

- KP481, a Water Dispersible Granular (WG) Formulation Containing DPX

- JE874 (254 g ai/kg) and Cymoxanil (266 g ai/kg): Acute Toxicity to the Hoverfly, Episyrphus balteatus DEG. (Diptera; Syrp hidae) in the Laboratory: Final Report: Lab Project Number: AMR4232

- 96: 96259/01

- NLEB. Unpublished study prepared by GAB Biotechnologie GmbH IFU Umweltanalytik GmbH. 30 p.

44946330 Kuhner, C. (1997) DPX

- KP481, a Water Dispersible Granular (WG) Formulati on Containing DPX

- JE874 (254 g ai/kg) and Cymoxanil (266 g ai/kg): Acute Toxicity to the Ground Beetle, Poecilus cupreus L. (Coleoptera, Carabidae) in the Laboratory: Final Report: Lab Project Number: AMR4233

- 96: 96259/01

- NLPC. Unpublished study prepared b y GAB Biotechnologie GmbH IFU Umweltanalytik GbmH. 29 p.

44946331 Thompson, B. (1999) Cymoxanil/Famoxadone (DPX

- KP481) 50 WG (25%:25%). An Extended Laboratory Study to Evaluate the Effects on the Green Lacewing, Chrysoperla carnea: Lab Project Number: D P

- 97

- 8: AMR4540

- 97. Unpublished study prepared by Agrochemical Evaluation Unit School of Biological Sciences University of Southampton. 24 p.

44946333 Beech, P.; Mead

- Briggs, M. (1998) Cymoxanil/Famoxadone (DPX

- KP481) 50 WG (25%:25%). An Extended Labora tory Study to Evaluate the Effects on the Ground Beetle, Poecilus cupreus: Lab Project Number: DP

- 97

- 10: AMR4539

- 97. Unpublished study prepared by Agrochemical Evaluation Unit School of Biological Sciences University of Southampton. 22 p.

44946334 Thompson, B. (1999) Cymoxanil/Famoxadone (DPX

- KP481) 50 WG (25%:25%). A Semi

- field Study to Evaluate the Effects on Aphid Parasitoids (Hymenoptera, Aphidiinae) in a Potato Crop: Lab Project Number: DP

- 97

- 3: AMR4542

- 97. Unpublished study prepared by Agroche mical Evaluation Unit School of Biological Sciences University of Southampton. 35 p.

44946332 Thompson, B. (1999) Cymoxanil/Famoxadone (DPX

- KP481) 50 WG (25%:25%): an Extended Laboratory Study to Evaluate the Effects on the Hoverfly, Episyrphus balteatu s: Lab Project Number: DP

- 97

- 9: AMR4541

- 97.53 Unpublished study prepared by Agrochemical Evaluation Unit School of Biological Sciences University of Southampton. 32 p.

44967202 Grove, A. (1996) Extended Laboratory Study Comparing the Effects of DPX

KX007 (Containing DPX

- JE874 and Cymoxanil) WG and SC Formulations on Typhlodromus pyri, Following Multiple Applications on Grapevine Leaves Under Greenhouse Conditions: Lab Project Number: AMR 3312

- 96: DU003TPS. Unpublished study prepared by Mitox Stichting Duur zame Plaagbestrijding. 38 p.

44946308 Forster, A. (1999) (Carbon

- 14) Famoxadone: To Assess the Toxicity to the Sediment Dwelling Phase of the Midge Chironomus riparius: Lab Project Number: 1538: DPT461: DUPONT1154. Unpublished study prepared by Huntingd on Life Sciences Ltd. 73 p.

44946304 Leva, S. (1999) An Evaluation of Aquatic Effects of Famoxadone Using Risk

Based Fish Studies: Lab Project Number: DUPONT

- 2038: DUPONT

- 1296: HL

1998

- 01530. Unpublished study prepared by E.I. du Pont de Nemours and Comp any. 91 p.

44946316 Hawkes, A.; Leva, S. (1999) Famoxadone: A Prospective Tier 1 Ecological Effects Assessment for Non

- Target Organisms: Lab Project Number: DUPONT

- 2117: DUPONT

- 1733. Unpublished study prepared by E.I. du Pont de Nemours and Company. 78 p.

44946317 Leva, S. ; Ball, M.; Hawkes, A. et al. (1999) Tier 1 Environmental Risk Assessment of DuPont DPX

- KP481 Fungicide (Containing 25% Famoxadone and 25% Cymoxanil) and Competitive Fungicides in the USA: Lab Project Number: DUPONT

- 2037. Unpublished study prepared by E.I. du Pont de Nemours and Company. 45 p.

44967203 Caley, C.; Knight, B.; Boyle, J. (1994) DPX

- JE874

- 221: Determination of Acute Toxicity (LC50) in Earthworms: Lab Project Number: 10206: 383475: IRI 383475. Unpublished study prepared by Inveresk Research International. 33
p.54

Appendix G: Health Effect Division’s MARC Document5556575859