Page 1 of 114 OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES UNITED ST AT ES ENVIRONMENT AL PROTECTION A GENCY

WASHINGTON D.C., 20460

PC Code: 000325 DP Barcode s : 357063

MEMORANDUM Date: January 28, 2010

SUBJECT: Metrafenone: Ecological Risk Assessment For Proposed Use on Grapes
FROM: Tanja Crk, M.A., B iologist

James A. Hetrick, Ph
. D
. , Senior Scientist Dana Spatz, Branch Chief Environmental Risk Branch III Environmental Fate and Effects Division (7507 P ) Office of Pesticide Programs
TO: Mary

Waller, Product Manager Fungicide B ranch Registration Division (7505P) Office of Pesticide Programs

This memorandum transmits the Environmental Fate and Effects Division’s (EFED) environmental risk assessment for the active ingredient , metrafenone, as a fungicide for uses on grapes to treat powd ery mildew; it is used for preventive but not curative measures. The proposed end
- use product Metrafenone 300 is a suspension concentrate containing 25.2% metrafenone. Ground (liquid) application is the proposed method of application. The maximum single application rate is 0.300 lbs a.i./A; at 6 applications per season, the seasonal maximum rate is 1.80 lbs a.i./A. The minimum application interval is 14 day s. While m etrafenone is expected to be slightly mobile, i ts major routes of degradation are aqueous photoly sis and aquatic metabolism, in both aerobic and anaerobic conditions. Soil metabolism is slow, with laboratory half
- lives of 6 months to a year and accumulation over two years observed in field studies. In aquatic environments, thePage 2 of 114

measured photo ly sis half
- life was 6.4 days and metabolism in both aerobic and anaerobic occurred with half

- lives of one to four weeks. Exposure is expected to be dominated by runoff and spray

drift. Metrafenone exposure may also result from off
- site movement in runoff w ater and on metrafenone
- bearing soil particulates to adjacent fields (soil erosion). The moderate Koc ’s (Koc 1073 to 22517 L/kg
- oc) of metrafenone suggest that leaching to ground water/recharge to surface water would not be a route of exposure. Long
- range transport of metrafenone in the gas phase is not considered a significant route of exposure. While the high log Kow (4.3 at 25 o C, pH 4) would suggest the potential for bioaccumulation, the lipid normalized BCF (between 140 and 530) indicates that metrafen one is not expected to accumulate in tissues of aquatic organisms. The results of this screening
- level assessment indicate a potential for direct adverse effects to non
- target mammals (dose
- based RQs 1.14
- 2.91) following chronic exposure; these RQs also e xceed the federall y listed species LOC. Due to the potential for direct adverse effects to mammals associated with the application of metrafenone on grapes, indirect effects may

consequently

affect other aquatic and terrestrial species. To reduce chronic risk to mammals, several components of the application protocol would have to change. For example, in order to have no chronic LOC exceedances ( i.e. , all RQs < 1) for mammals, the minimum single application rate (0.2 lbs a.i./A) would have to be cut b y 25% ( i.e. , to 0.15 lbs a.i./A) yet considered the maximum instead, the application interval would have to nearly

double (from 14 day s up to 26 day s), and the maximum allowed number of applications would have to be cut from 6 to 5. Alternatively, in order to have no chronic LOC exceedances for mammals, the minimum single application rate (0.2 lbs a.i./A) can still be applied yet considered the maximum instead, but the application interval would have to nearly double (from 14 days up to 26 day s), and the maximum number of applications would have to be cut b y 50% ( i.e. , from 6 to 3). Furthermore, in order to have no chronic LOC exceedances in nearly all cases for mammals

–the one exception being an exceedance for the 15g size glass consuming short grass where the c alculated RQ is 1.02

– the minimum single application rate (0.2 lbs a.i./A) would be changed to the maximum single application rate and the application interval (14 day s) could remain as currently prescribed b y the label, but the maximum number of applicat ions would have to be reduced from 6 to 2. Data were either not submitted or were deemed invalid for freshwater invertebrates and marine/estuarine fish via chronic exposure. Without data, risk cannot be ruled out for these taxa (either non
- listed or federall y listed species). Non
- definitive endpoints

– in this case, where total concentrations were estimated instead of the preferred dissolved concentrations in the majority of aquatic studies on metrafenone

– suggest potential chronic risk to federall y lis ted freshwater fish and acute risk to federally

listed marine/estuarine invertebrates. More detailed risk conclusions are provided in the environmental risk assessment document.
Data NeedsPage 3 of 114

The ecotoxicity

and environmental fate data needs are summarized in Tables 1 and 2 below. Further explanation and characterization of these data needs can be found in the executive summary

of the ecological risk assessment.
Table 1. Ecological Toxicity Data Gaps Study Reason 850.1075 Acute toxicity freshwater fish Non
- definitive endpoint w/effects observed 850.1400 Freshwater fish early
- life stage (chronic) Non
- definitive endpoint w/effects observed 850.1300 Aquatic freshwater invertebrate life
- cycle (chronic) Invalid, CFR data gap 850.1025 Acute marine/estuarin e invertebrate (oyster) Or 850.1035 Acute marine/estuarine invertebrate (mysid) Non
- definitive endpoint w/effects observed OECD 218 Freshwater invertebrate w hole sediment study (chronic) Invalid, CFR data gap 850.4400 Aquatic vascular plant growth, Tier II Non
- definitive endpoint w/effects observed 850.5400 Aquatic non
- vascular plant grow th, Tier II Non
- definitive endpoint w/effects

observed 850.2100 Avian acute oral toxicity test (passerine species) Not submitted, CFR data gap 850.3020 Honeybee a cute contact toxicity (on TEP) Address formulation uncertainty 850.4100 Seedling Emergence, Tier II (on TEP) Address formulation uncertainty 850.4150 Vegetative Vigor, Tier II (on TEP) Address formulation uncertainty

Table 2. Environmental Fate Data Gaps 835.6100 Independent Laboratory ValidationsPage 4 of 114



## NEW CHEMICAL REGISTRATION

(Section 3) 

## ECOLOGICAL RISK ASSESSMENT Metrafenone: Fungicide USEPA PC # 000325

Chemical Name(s) : (3
- bromo
- 6
- methoxy
- 2
- methylphenyl)(2,3,4
- trimethoxy
- 6
-

methylphen yl )methanone (CAS) 3’
- bromo
- 2,3,4,6’
- tetramethoxy
- 2’,6
- dimethylbenzophenone (IUPAC) Chemical Abstracts Service (CAS) Number : 220899
- 03
- 6 Chemical Famil y : Benzophenone fungicide Pesticidal Mode of Action : Inhibits growth of mycelium on the leaf surface, leaf penetration, formation of haustoria, and sporulation
. Li kel y affects actin proteins which play a role in cell function and cell division. Proposed En d
- use Product : Metrafenone 300 SC (EPA Reg.No.7969
- xxx); Suspension Concentrate, 25.2% (2.5 lbs a.i./gallon) Target Pest(s) : Powdery mildew produced by Uncinula necator Proposed Target Crop(s) : Grapes Ris k Assessors : Tanja Crk, MA, Biologist

James A. Hetrick, PhD, Senior Scientist E nvironmental Risk Branch III Environmental Fate and Effects Division Secondary

Reviewers : Pamela Hurley , PhD, Toxicologist

Environmental Risk Branch III Environmental Fate and Effects Division Through : Dana Spatz, Branch Chief

Environmental Risk Branch III Environmental Fate and Effects DivisionPage 5 of 114 

### Table of Contents I. EXECUTIVE SUMMARY ................................ ................................ ...................... 5 A. Nature of the Chemical Stressor
................................ ................................ ............. 5 B. Potential Risks to Non
- target Organisms
................................ ................................ 5 C. Environmental Fate Summary
................................ ................................ ................ 6 D. Ecological Effe cts Summary
................................ ................................ ................... 7 E. Uncertainties and Data Gaps
................................ ................................ ................... 8 1. Environmental Fate and Exposure
................................ ................................ ...... 8 2. Ecological Effects Data
................................ ................................ ....................... 9 F. Endangered Species Considerations
................................ ................................ .... 12 II. PROBLEM FORMULATION ................................ ................................ .......... 13 A. Nature of Regulatory Action
................................ ................................ ................. 13 B. Stressor Source and Distribution
................................ ................................ .......... 13 1. Nature of the Chemical Stressor
................................ ................................ ... 13 a. Mode of Action (MoA) of Metrafenone
................................ ...................... 1 5 b. Reactions of Metrafenone in the Environment
...... 1 5 Error! Bookmark not defined. Error! Bookmark not defined. 2. Overview of Pesticide Usage
................................ ................................ ........... 15 C. Receptors
................................ ................................ ................................ ............... 15 1. Aquatic and Terrestrial Effects
................................ ................................ ......... 15 2. Ecosy stems Potentiall y at Risk
................................ ................................ ......... 17 D. Assessment Endpoints
................................ ................................ .......................... 17 E. Conceptual Model
................................ ................................ ................................ . 17 1. Risk Hy

pothesis
................................ ................................ ................................ 17 2. Co nceptual Diagram
................................ ................................ ......................... 18 F. Analy sis Plan
................................ ................................ ................................ ....... 19 1. Conclusions from Previous Risk Assessments
................................ ................. 19 2. Preliminary

I dentification of Data Gaps
................................ ........................... 19 3. Measures of Exposure and Effects
................................ ................................ .... 23 a. Aquatic Exposure Models
................................ ................................ ............. 24 b. Terrestrial Exposure Models
................................ ................................ ......... 24 III. ANALYSIS ................................ ................................ ................................ .......... 28 A. Use Characterization
................................ ................................ ............................. 28 B. Exposure Characterization
................................ ................................ .................... 28 1. Environmental Fate and Transport
................................ ................................ .... 28 2. Measures of Aquatic Exposure ................................ ................................ ......... 31 a. Aquatic Exposure Modeling
................................ ................................ ......... 31 b. Aquatic Exposure Monitoring and Field Data
................................ .............. 37 c . Aquatic Bioaccumulation Assessment
................................ .......................... 37 3. Measures of Terrestrial Exposure
................................ ................................ ..... 36 a. Terrestrial Exposure Modeling
................................ ................................ ..... 36 C. Eco logical Effects Characterization
................................ ................................ ...... 38 1. Aquatic Effects Characterization
................................ ................................ ...... 38Page 6 of 114 a. Aquatic Animals
................................ ................................ ........................... 38 (1) Acute Effects
................................ ................................ ........................ 38 (2) Chronic Effects
................................ ................................ ..................... 47 b. Aquatic Plants
................................ ................................ ............................... 49 2. Terrestrial Effects Characterization
................................ ................................ .. 55 a. Terrestrial Animals
................................ ................................ ....................... 55 (1) Acute Effects
................................ ................................ ......................... 55 (2) Chronic Effects
................................ ................................ ..................... 62 b. Terrestrial Plants
................................ ................................ ........................... 67 IV. RISK CHARACTERIZATIO N ................................ ................................ ......... 68 A. Risk Estimati on - Integration of Exposure and Effects Data
............................... 68 1. Risk to Aquatic Animals and Plants
................................ ................................ . 68 a. Aquatic Animals
................................ ................................ ........................... 68 (1) Risk Following Acute Exposure
................................ ........................... 68 (2) Risk Following Chronic Exposure
................................ ........................ 69 b. Aquatic Plants
................................ ................................ ............................... 70 2. Risk to Terrestrial Animals and Plants
................................ ............................. 70 a. Terrestri al Animals
................................ ................................ ....................... 70 (1) Risk Following Acute Exposure
................................ ........................... 71 (2) Risk Following Chronic Exposure
................................ ........................ 72 b. Terrestrial Plants
................................ ................................ ........................... 75 B
. Risk Description
................................ ................................ ................................ .... 75 1. Risk to Aquatic Animals and Plants
................................ ................................ . 75 a. Aquatic Animals
................................ ................................ ........................... 75 (1) Risk Following Acute Exposure
................................ ........................... 75 (2) Risk Following Chronic Exposure
................................ ........................ 78 b. Aquatic Plants
................................ ................................ ............................... 79 2. Risk to Terrestrial Animals and Plants
................................ ............................. 80 a. Terrestrial Animals
................................ ................................ ....................... 80 (1) Risk Following Acute Exposure
................................ ........................... 80 (2) Risk Following Chronic Exposure
................................ ........................ 82 b. Terrestrial Plants
................................ ................................ ........................... 83 3. Review of Incident Data
................................ ................................ ................... 84 4. Endocrine Effects
................................ ................................ .............................. 84 5. Federall y Threatened and Endangered (Listed) Species..
................................ . 85 a. Action Area
................................ ................................ ................................ ... 86 b. Taxonomic Groups Potentially at Risk
................................ ......................... 86 (1) Discussion of Risk Quotients
................................ ................................ 89 (2) Probit Dose Response Relationship
................................ ...................... 89 (3) Data Related to Under
- represented Taxa
................................ .............. 9 0 (4) Implications of Sublethal Effects
................................ .......................... 90 c. Indirect Effects Anal ys is
................................ ................................ ............... 92 d. Critical Habitat
................................ ................................ .............................. 93 e. Co
- occurrence Anal ys is
................................ ................................ ................ 94 C. Description of Assumptions, L imitations, Uncertainties, Strengths and Data Gaps .................................................................................................95Page 7 of 114

1. Assumptions, L imitations, and Uncertainties Related to Exposure For All Taxa .............................................................................................95 a. Maximum Use Scenario............................................................95 2. Assumptions, L imitations and Uncertainties Related to Exposure For Aquatic Species
................................ ................................ ................................ ...................... 95 a. Environmental Fate Studies.........................................................95 b. Aquatic Exposure Model
................................ ................................ .............. 95 b. Bioaccumulation Modeling
................................ ................................ ........... 96 3. Assumptions, L imitations and Uncertainties Related to Exposure for Terrestrial Species
................................ ................................ ................................ ...................... 96 a. Location of Wildlife Species
................................ ................................ ........ 96 b. Routes of Exposure
................................ ................................ ....................... 96 c. Dietary

Intake and Other Limitations of Oral Studies in Terre strial Species 96 d. In cidental Releases Associated With Use
................................ ..................... 98 e. Residue Levels Selection
................................ ................................ .............. 99 f. TerrPlant Model
................................ ................................ ............................ 99 4. Assumptions, L imitations and Uncertainties Related to Effects Assessment
.. 99 a . Sublethal Effects
................................ ................................ ........................... 99 b
. Age Class and Sensitivity of Effects Thresholds
................................ .......... 99 c . Use of Most Sensitive Species Tested
................................ ........................ 100 5. Assumptions, L imitations, Uncertainties, Strengths and Data Gaps Related to the Acute and Chronic LOC’s
................................ ................................ ................. 100 V. LITERATURE CITED ................................ ................................ ........................ 101 VI. APPENDICES ................................ ................................ ................................ ... 109 VII. LIST OF FIGURES......................................................................109 VIII. LIST OF TABLES........................................................................109Page 8 of 114

I. Executive Summary

A. Nature of the Chemical Stressor Metrafenone (3
- bromo
- 6
- methoxy
- 2
- methylphen yl)(2,3,4
- trimethoxy
- 6
- methylphen yl )methanone; CAS Reg. No. 220899
- 03
- 6 ) is a new pesticide active ingredient submitted for registration in the United States. Metrafenone is a benzophenone fungicide with resistance code U8 (unkn own mode of action) . What is known is that the chemical inhibits growth of mycelium on the leaf surface, leaf penetration, formation of haustoria, and sporulation of the target fungus, Uncinula necator (EPA Pesticide Fact Sheet 2006)

. Metrafenone likely af fects actin proteins which play a role in cell function and cell division (Opalski et al. 2006). Ithas a local inhibition effect; in other words, it is not sy stemic and not a contact killer. As a new pesticide active ingredient, the actual usage of metr afenone is not known. The end
- use product Metrafenone 300 SC is proposed for use on grapes to treat powdery mildew ; it is used for preventive but not curative measures . Ground (liquid) application is the proposed method of application. The maximum single a pplication rate is 0.300 lbs a.i./A; at 6 applications per season, the seasonal maximum rate is 1.80 lbs a.i./A. The minimum application interval is 14 day s.

B. Potential Risks to Non - target Organisms The results of this screening
- level assessment indicate a potential for direct adverse effects to non
- target mammals ( dose
- based RQs 1.14
- 2.91) following chronic exposure ; these RQs also exceed the federall y listed species LOC. Due to the potential for direct adverse effects to mammals associated with the appli cation of metrafenone on grapes , indirect effects may

consequently

affect other aquatic and terrestrial species
. Data were either not submitted or were deemed invalid for freshwater invertebrates and marine/estuarine fish via chronic exposure. Without data , risk cannot be ruled out for these taxa (either non
- listed or federall y listed species). Non
- definitive endpoints

– in this case, where total concentrations were estimated instead of the preferred dissolved concentrations in the majority of aquatic studi es on metrafenone

– suggest potential chronic risk to federall y l isted freshwater fish and acute risk to federally listed marine/estuarine invertebrates. Comparison of the non
- definitive endpoints with aquatic EECs indicates potential risk to the given fe derally listed taxa (see Section I.F below , Table 3 ) but not the non
- listed taxa summarized in Table 1 and Table 2
.Page 9 of 114

Table 1 . Summary of Environm ental Risk Conclusions for Aquatic Animals and Plants from Metrafenone Use on Grapes at the Maximum P roposed Application Rate (0.3 lb a.i. /A, Assuming 6 Application s /Year) * Taxonomic Group Assessment

Endpoint Summarized Risk Characterization and Important Uncertainties Freshwater Fish and Aquatic Phase Amphibians Mortality Ac ute risk i s not expected (from technical grade active ingredient, metabolites, and EU/UK formulation)
. Reproduction, grow th et c. Chronic risk is not expected.
Freshwater Invertebrates Mortality Ac ute risk is not expected (from technical grade active ingredient, m etabolites, and EU/UK formulation). Reproduction, grow th etc. No acceptable studies available. Chronic risk cannot be precluded
. Marine/ Estuarine Fish Mortality Ac ute risk is not expected.

Reproduction, grow th etc. No studies submitted. Chronic risk cannot be precluded
. Marine/ Estuarine Invertebrates Mortality Ac ute risk is not expected.

Reproduction, grow th etc. Chronic risk is not expected.
Aquatic Plants Ac ute Risk Risk to vascular species is not expected from technical grade active ingredient . In addition, risk to non - vascular species is not expected (from the technical grade active ingredient, metabolites, and EU/UK formulation)
. * Consult ‘Risk Description’ section for further details
. Also, risk in this table implies risk to technical grad e active ingredient unless otherwise specified that metabolites and formulations were assessed as well.

Table 2 . Summary of Environm ental Risk Conclusions for Terrestrial Animals and Plants from Me trafenone Use on Grapes at the Maxim umProposed Application Rate (0. 3 lb s a.i. /A, Assuming 6 Application s /Year) * Taxonomic Group Risk Endpoint Summarized Risk Characterization and Important Uncertainties Birds, Reptiles and Terrestrial Phase Amphibians Mortality Ac ute risk is not expected.

Reproduction, grow th etc. Chronic risk is not expected.

Mammals Mortality Ac ute risk is not expected.

Reproduction, grow th etc. Chronic risk is expected
. Non
- target Invertebrates Ac ute Risk Ac ute risk to honeybees is not expected. Acute ri sk to earthworms (from the technical grade active ingredient, a metabolite, and EU/UK formulation) is not expected. Terrestrial Plants Ac ute Risk Risk to terrestrial plants is not expected (from EU/UK formulation)
. * Consult ‘Risk Description’ section fo r further details
. Also, risk in this table implies risk to technical grade active ingredient unless otherwise specified that metabolites and formulations were assessed as well.

C. Environmental Fate Summary While m etrafenone is expected to be slightly mo bile, i ts major routes of degradation are aqueous photoly sis and aquatic metabolism, in both aerobic and anaerobic conditions.Page 10 of 114

Soil metabolism is slow, with laboratory half
- lives of 6 months to a year and accumulation over two years observed in field studies. In aquatic environments, the measured photol ys is half
- life was 6.4 days and metabolism in both aerobic and anaerobic occurred with half

- lives of one to four weeks. Soil photolysis and anaerobic aquatic metabolism of metrafenone led to one major degradate, CL377160 [Methanone, (3
- bromo
- 6
- methoxy
- 2
- methylphenyl)(3
- hydrox y2,4
- dimethoxy
- 6
- methylphenyl)
- ], and anaerobic aquatic metabolism also led to six other major degradates, but all were either unidentified or only tentativel y identified. In additio n, there were many minor degradates, which were formed at low levels individually

but reached substantial amounts as groups. Tier II aquatic exposure modeling was conducted for parent metrafenone and metrafenone residues (metrafenone+ extractable residu es) (Table 1 1 ). This modeling approach was used to address uncertainties associated with identification of metrafenone residues in soil and sediment. The highest aquatic EECs for metrafenone were 11.70 μg/Lfor the daily

peak, 8.82 μg/L for the 21 day average, and 6.21 μg/Lfor the 60 day average. The highest aquatic EECs for total metrafenone residues were 20.22 μg/L for the daily peak, 17.67 μg/L for the 21 day average, and 16.98 μg/L for the 60 day av erage. No monitoring data are available to compare with model estimates. Bioaccumulation modeling was conducted because metrafenone has a log octanol:water coefficient > 4. Maximum residue concentrations in fish are expected to range from 17,636 to 19,58 6 μg/kg
- ww. D. Ecological Effects Summary Aquatic Organisms The greatest amount of uncertainty in the assessment stems from aquatic studies which were largel y based on total concentrations (both dissolved and undissolved) of the test compound. In all case s (except for the chronic study on the saltwater m ys id , but including aquatic plants ), the risk quotient values were not calculated. However, g iven comparisons of the total concentrations for most available studies and soluble concentrations for the saltwater m ys id (chronic) and sheesphead minnow (acute) to respective EEC values the implication is that acute and chronic risk (including sublethal effects) to aquatic organisms (including aquatic plants) is not expected as a result of metrafenone use on grapes . However, the taxa for which studies were either submitted and deemed unacceptable (chronic freshwater invertebrate studies) or not submitted at all (chronic marine/estuarine fish), the risk as a result of metrafenone use cannot be precluded. Terrestrial Organisms The acute oral avian studies indicated no effects; the acute dietary avian studies indicated a significant change in body weight that was not associated with a dose
- response pattern. In the acute mouse study

on the technical grade active ingredient, only one mortality

was reported. Therefore, no implications with lethal or sublethal acute effects can be madePage 11 of 114

for either avian or mammalian taxa. Metrafenone is classified as ‘practically non - toxic’ to ho ney bees and non
- lethal to earthworms up to the limit concentrat ion. Therefore, the implication is that acute risk to terrestrial invertebrates is not expected as a result of metrafenone use on grapes. In addition, no terrestrial plant risks are expected as a result of use of the EU/UK formulation; h owever, no data on terrestrial plants are available on the U.S. formulation. The avian chronic toxicity endpoint (NOAEC 848 mg a.i./kg diet) based on egg production and hatchability did not yield chronic LOC exceedances. The most sensitive chronic mammal ian endpoint (NOAEL 35.9 mg/kg bw/day) based on decreased body weights and body weight gain in F 1 males as well as body weights in F 1 and F 2 females, however, exceeded the chronic LOC, which implies that sublethal chronic effects on mammals are expected un der field conditions. Therefore, given the LOC exceedance chronic risk to mammals is expected as a result of metrafenone use on grapes.

E. Uncertainties and Data Gaps

1. Environmental Fate and Exposure All but one of the environmental fate studies required t o support the registration of metrafenone for use on grapes were submitted. Independent Laboratory Validations for the methods submitted for anal ys is of metrafenone in soi l and water remain a data gap. These data gaps fall under the terrestrial field diss ipation study guideline (835.6100). For a list of submitted environmental fate studies for metrafenone see Appendix F
. All of the environmental fate studies for the parent compound were determined to be s cientificall y valid and therefore results from all of the studies can be used to characterize the mobility

and rates of transformation of metrafenone. However, many of the metabolism studies have major uncertainties in the identification and pattern of formation and decline of transformation products. In all of the aquatic metabolism studies, between 57% and 65% of the applied radioactivity remains unidentified with incomplete characterization, and in two aerobic soil metabolism studies, 15% and 44% of the applied radioactivity

is unidentified. This inc ludes at least four major degradates that individually

reach levels of 11% to 35% of the applied. Other transformation products appear as groups of up to 15 components, in some cases characterized as each being <5% of the applied radioactivity , but in oth er cases, some individual components make up 9% to 10% of the applied. Even when individual components can all be classified as minor degradates, these groups represent such a large portion of the applied radioactivity overall that the possibility

that th ey may have some impact as a group cannot be precluded despite their lower individual levels. This is especially true given that the degradation pathway s suggest that groups of degradates may have a high degree of structural similarity and so may

have sim ilar fate and effects behavior. Without information to adequatel y characterize the degradates, it was necessary to assume that they

are of equal toxicity to the parent in order to quantify risks for metrafenone extractable residues.Page 12 of 114 In addition to the studies submitted by the registrant, EFED was provided with a Draft Assessment Report (DAR) on Metrafenone written by the United Kingdom. That assessment reports that the long dissipation time observed in field studies triggered a requirement for longer ter m field accumulation studies. Two years into those five year studies, results show that metrafenone appears to be accumulating, and that metrafenone residues have been detected as deep as 20
- 30 cm below the surface. These studies would provide useful infor

mation regarding the environmental fate of metrafenone and would assist in reducing uncertainties. 2. Ecological Effects Data The submitted ecotoxicity database is incomplete. The greatest amount of uncertainty in the assessment stems from aquatic studies which were largely based on total (both dissolved and undissolved) concentrations of test compound ; that is, the concentrations were measured without centrifugation even though precipitate was observed or test was conducted at the solubility limit of the m etrafenone technical grade active ingredient; the solubility limits of the metabolites are unknown . To reduce uncertainty the majority of the toxicity studies, which are considered supplemental, and cannot be used in a quantitative risk estimation would ne ed to be redone ; especiall y those where mortality

or sublethal effects were observed
. These aquatic studies are specified below. For a list of submitted ecological effects studies for metrafenone see Appendix G
. The following studies are considered data n eeds : Aquatic studies Given the freshwater fish studies on metrafenone technical grade active ingredient and assuming that the concentrations in the environment reach the solubility limit, the effect of the compound is likely to be low. However, a ccording to model estimated EECs (which include metrafenone and metrafenone residue scenarios : 0.00153
- 0.02 mg/L ), levels of metrafenone (TGAI, TEP) 1 at the solubility limit (0.2
- 0.5 mg/L at 12 o C) and metrafenone metabolites at the tested concentrations are not expected to occur in the environment given the proposed grape use. Therefore, acute risk to freshwater fish and aquatic
- phase amphibians is not expected as a result of metrafenone use on grapes. In addition, although the EU/UK formulation

– with which the submitted studies were conducted

– closel y matches the U.S. formulation ( i.e. , BAS 560 03F) it is still not its equivalent. Therefore, the effect of the U.S. formulated product on freshwater fish and aquatic
- phase amphibians is not known. T o reduce uncertainty

in characterizing risk, which is currentl y based on total concentrations, the freshwater fish studies on bluegill sunfish ( Lepomis macrochirus ) are requested to make same species comparisons for acute and chronic values. Bluegill was chosen over the rainbow trout due to greater sensitivity (on an acute basis) of the bluegill to the TGAI relative to the trout. Since the acute marine/estuarine fish study is acceptable and given the above two studies, the acute to chronic ratio can be utilized to es timate

1 TGAI: technical grade active ingredient; TEP: typical end
- use product (formulation)Page 13 of 114

marine/estuarine chronic endpoints, negating the need to fill this data gap. Special emphasis must be placed on centrifuging the test samples prior to anal yt ical determination of the test compound.

 Acute: F reshwater fish toxicity (96
- hour L C 50 for Lepomis macrochirus ) (850.1075; 72
- 1), TGAI  Chronic: Fish earl y- life stage (freshwater: Lepomis macrochirus ) (850.1400; 72
- 4), TGAI Although acute freshwater invertebrate studies were based on total concentrations, no effects were observed with the TGAI , negating the need to request additional data. However, a chronic freshwater invertebrate data gap still exists since the two reviewed studies were d eemed invalid
.
 Chronic: Aquatic invertebrate life cycle (freshwater: Daphnia magna ) (850.1300; 72
- 4), TGAI Effects were observed in both acute marine/estuarine invertebrate studies with the TGAI on the eastern o ys ter ( Crassostrea viginica ) and saltwater m ys id ( Americamysis bahia ) but the endpoints are based on total concentrations. Therefore, should concentrations in the environment reach the solubility limit, the acute risk to marine/estuarine invertebrates may be expected
. However, according to the model estimated EECs (0.00153
- 0.02 mg/L, which includes metrafenone and total metrafenone residue scenarios ), levels of metrafenone at the solubility limit are not expected to occur in the environment given the proposed grape use. Given these studies and assuming that metrafenone concentrations in the environment are not likely to reach the solubility

limit, th e acute risk to marine/estuarine invertebrates is not expected. However, to reduce uncertainty in characterizing risk, either study is requested to be redone with special emphasis on centrifuging the test samples prior to anal yt ical determination of the te st compound.

 Acute: Marine/estuarine invertebrate either Crassostrea virginica (850.1025; 72
- 3) or Americamysis bahia (850.1035; 72
- 3), TGAI A non
- guideline chronic midge study ( Chironomus riparius ) with metrafenone technical (97.1%) was deemed invalid on the basis of low negative control emergence. Therefore, a chronic freshwater invertebrate whole sediment study is requested . A protocol should be submitted for approval prior to study initiation. The protocol should includ e spiked sediment. The whole se diment study is requested because metrafenone has a high logKow value (4.3 at 25 o C, pH 4) and a high aerobic soil half life (> 4 months), which indicates that the compound may

partition to sediment and persist.

 Chironomus dilutus (freshwater) using TGAI. Consult EPA Test Method 100.5 Life
- cycle Test for Measuring the Effects of Sediment Associated Contaminants on Chironomus dilutus (formerl y Chironomus tentans ) and OECD Guideline 218 Sediment
- Water Chironomid Toxicity Test Using Spiked SedimentPage 14 of 114

Non
- target aquatic plant studies were also based on total concentrations leading to uncertainty in exposure concentrations and thus endpoint values. H ad valid endpoints ( i.e. , those based on dissolved concentrations) been determined using these studies, they would l ikely

be greater than the highest model predicted concentration in the environment, which implies that risk to vascular and non
- vascular species is not expected as a result of metrafenone use on grapes. However, w ithout centrifugation, the amount of chemic al that is freel y dissolved and bioavailable cannot accurately be determined
. Therefore, vascular and non
- vascular aquatic plant studies are requested with special emphasis placed on centrifuging the test samples prior to anal yt ical determination of the te st compound. In addition, cyanobacteria yielded no effects given total concentrations and does not need to be redone.

 Aquatic vascular plant growth ( Lemna spp.), Tier II (850.4400), TGAI  Aquatic non
- vascular plant growth, Tier II (850.5400), TGAI T errestrial Studies An avian acute oral toxicity test in passerine species is required. Passerines are the most common birds (in terms of numbers and number of species) in the United States. Many utilize agricultural fields, forests, residential areas an d surrounding areas, and, therefore, have the potential to be exposed to pesticides used in agricultural, forest, and residential settings. It is likely

that, for the requested use patterns, passerines are more likely to be exposed to metrafenone than upl and game species and waterfowl. Passerines are smaller and have a higher energy requirement than larger
- sized birds. As such, passerines may be more sensitive than other birds.

 Passerine bird toxicity study (EPA approved protocol is required prior to s tudy initiation) : Avian acute oral toxicity test (850.2100, 71
- 1), TGAI Formulated Product Testing The available formulation product studies were conducted using three different UK/EU formulated products ( i.e. , BAS 560 00F, BAS 560 01F, and BAS 560 02F), one of which (BAS 560 00F) closel y matches the U.S. formulation ( i.e. , BAS 560 03F). Formulation studies in this assessment are based on BAS 560 00F because data on the U.S. formulation were not submitted. In order to eliminate uncertainty in effects characterization of formulated products used within the U.S. on given taxa, future registrant submitted studies should be based on the U.S. formulation. At this time the effect of the U.S. formulation on given taxa is not known , however, greater toxicity of th e EU/UK formulation on the honey bee relative to the TGAI was observed
. Similarly , data submitted for terrestrial plants is based on the EU/UK formulation. As a result, the following studies are requested:  Honey

bee acute contact toxicity (850.3020, 141
- 1), TEP  Seedling emergence , Tier II (850.4225 , 123
- 1 ), TEP  Vegetative vigor, Tier II (8 50.42 50, 123
- 1 ), TEPPage 15 of 114 F. Endangered Species Considerations Table 3 summarizes the listed species at risk associated with either direct or indirect effects following applicatio n of metrafenone for the proposed uses. Concerns For Federally Listed as Endangered and/or Threatened Species Table 3. Listed Species Risks Associated With Direct or Indirect Effects from Metrafenone use on Grapes at the Maximum Proposed Application Rat e (0.3 lbs a.i./A, Assuming 6 Applications/Year)

Listed Taxon Direct Effects Indirect Effects Terrestrial and semi
- aquatic plants
- mo nocots No Yes from effects to mammals Terrestrial and semi
- aquatic plants

– dicots No Yes from effects to mammals Terrestrial invertebrates No Yes from effects to mammals Birds No Yes from effects to mammals, FW fish, FW inverts, M/E fish, M/E inverts (mollusks) Terrestrial
- phase amphibians No Yes from effects to mammals Reptiles No Yes from effects to mammals, FW fish, FW inverts, M/E fish, M/E inverts (mollusks) Mammals Yes for chronic 1 Yes from effects to mammals, FW fish, FW inverts, M/E fish, M/E inverts (mollusks) Aquatic non
- vascular plants No Yes from effects to mammals, FW fish, FW inverts, M/E fish, M/E inverts (mollusks) Aquatic vascular plants No Yes from effects to mammals, FW fish, FW inverts, M/E fish, M/E i nverts (mollusks) Freshwater (FW) fish Yes for chronic 2 Yes from effects to mammals, FW fish, FW inverts, M/E fish, M/E inverts (mollusks) Aquatic
- phase amphibians Yes for chronic 3 Yes from effects to mammals, FW fish, FW inverts, M/E fish, M/E inverts (mollusks) Freshwater (FW) invertebrates Yes for chronic 4 Yes from effects to mammals, FW fish, FW inverts, M/E fish, M/E inverts (mollusks) Marine/estuarine (M/E) fish Yes for chronic 4 Yes from effects to mammals, FW fish, FW inverts, M/E fish, M/E i nverts (mollusks) Marine/estuarine (M/E) invertebrates (mollusk) Yes for acute 5 , No for chronic 6 Yes from effects to mammals, FW fish, FW inverts, M/E fish, M/E inverts (mollusks) 1 The chronic LOC is exceeded on a dose basis for mammals in all size c lasses eating short grass, for the 15 and 35 gram size classes eating tall grass and broadleaf plants / small insects. The chronic LOC on a dietary basis is not exceeded for any o f the food categories. 2 The total concentration based endpoint (NOAEC: 0.1 18 mg total a.i./L) for the chronic freshwater fish (fathead minnow) study (MRID 47267449) with an effect on post
- hatch survival is approximately 7x greater than the highest estimated EEC (0.016 mg/L), hence risk to federally listed freshwater fish cannot be precluded. 3 Results from freshwater fish used as surrogate for assessing risk to aquatic
- phase amphibians 4 Studies not submitted or invalid for which risk cannot be precluded. 5 Mollusk (Eastern oyster); 6 Saltwater mysidPage 16 of 114

II. Problem Formulation The purpose of this problem formulation is to provide the foundation for the ecological risk assessment being conducted for the fungicide metrafenone. As such, it articulates the purpose and objectives of the risk assessment, evaluates the nature of the problem, and provides a plan for anal yzing the data and characterizing the risk (EPA, 1998).

A. Nature of Regulatory Action Metrafenone is a new pesticide active ingredient being proposed as a fungicide to control powdery mildew on grapes. As a new active ingre dient submitted for registration, there are no previously

prepared ecological risk assessments by th e Agency

for metrafenone uses. However, the European Commission has issued a Dossier for Metrafenone 2 (DAR 2005 ). B. Stressor Source and Distribution The stressor is the metrafenone and its unidentified, extractable degradation products when applied to grapes to control powdery mildew. Therefore, metrafenone could potentially

be used an ywhere in the United States where grapes are grown.

1. Nature of the Chemica l Stressor Figure 1 provides the chemical structure of metrafenone. Table 4 identifies the phy sical and chemical properties of metrafenone from experimental data
. Figure 1. Chemical Structure of Metrafenone

2 EC Directive 91/414.Page 17 of 114

Table 4. Environmental Fate Properties of Metrafenone PARAMETER VALUE(S) (units) SOURCE COMMENT Chemical Name (3
- Bromo
- 6
- methoxy
- 2
- methylphenyl)(2,3,4
- trimethoxy
6
- methylphenyl)
- methanone – –
Molecular Formula C 19 H 21 BrO 5 . Molecular Weight 409

_ – Solubility (20 o C) 0.474 mg/L or ppm MRID: 46415711 “Slightly soluble” according to FAO Classification Va por Pressure (20 o C) 1.15 x 10 - 6 mmHg MRID: 46415713

– Henry’s Law constant 1 .3 x 10 - 6 atm- m3 /mole Estimated from vapor pressure and water solubility. pKa (20 o C) None MRID: 46415714

– Octanol
- Water Partition Coefficient (Log KOW , at 25 o C, pH 4) 4.3 MRID: 46415715

– Hydrolysis Half

- life (pH 5, 7, 9; (50 o C)) Stable MRID: 47267422 Stable at all pHs. Aqueous Photolysis Half
- life (pH 5) t 1/2 = 6.4 days MRID: 47267423 Value corrected to represent natural sunlight at 40°N latitude; uncorrected lab half
life of 3.2 days (continuous irradiation; xenon lamp). Soil Photolysis Half

- life t 1/2 = 31 days MRID: 47267424

– Aerobic Soil Metabolism Half
- life Silt loam: t 1/2 = 178
- 277 d Sandy loam: t 1/2 = 277, 365 d Clay loam: t 1/2 = 299, 330 d Loamy sand: t 1/2 = 182 d DT 50 = 160

– 270 d MRIDs: 47267425 472674 26 47267427 8 systems, 4 conducted with

foreign soils. In 2 studies metrafenone residues exceeded 50% at study termination (120 & 210 d) Anaerobic Aquatic Metabolism Half
- life t 1/2 = 21.6 d, 18.0 d DT 50 = 15 d, 3 d MRIDs: 47267429 47267431 –
A erobic Aquatic Metabolism Half
- life t 1/2 = 27.3 d, 24.1 d DT 50 = 10 d, 11 d MRID: 47267430

– Organic Carbon Partition Coefficient (KOC ) 1073, 2230, 2331, 22517, 2792 mL/g OC MRID: 47267420 “Slightly mobile” according to FAO Classification Soi l Partition Coefficient (Kd) 15.1, 36.5, 40.1, 42.0, 86.5 mL/g MRID: 47267420
-- Terrestrial Field Dissipation t 1/2 =144 d, 161 d, 210 d, 161 d MRID 47267432 Field studies were conducted in WA, ON,CA, FL Bioaccumulation in Fish BCF: 140 to 530 MRID 472 67450 Lipid Normalized BCFPage 18 of 114 a. Mode of Action (MoA) of Metrafenone Metrafenone is a benzophenone fungicide. What is known is that the chemical inhibits growth of mycelium on the leaf surface, leaf penetration, formation of haustoria, and sporulation of the target fungus, Uncinula necator (EPA Pesticide Fact Sheet 2006)

. Metrafenone likel y affects actin proteins which play a role in cell function and cell division (Opalski et al. 2006)
. b. Reactions of Metrafenone in the Environment Metrafenone is expected to be slightly mobile. Its major routes of degradation are aqueous photoly sis and aquatic metabolism, in both aerobic and anaerobic conditions. Soil metabolism is slow, with laboratory half
- lives of 6 months to a year and accumulation over two years observe d in field studies. In aquatic environments, the measured photol ys is half
- life was 6 .4 days and metabolism in both aerobic and anaerobic occurred with half

- lives of one to four weeks. Soil photolysis and anaerobic aquatic metabolism of metrafenone led to one major degradate, CL377160, and anaerobic aquatic metabolism also led to six other major degradates, but all were either unidentified or onl y tentatively identified. Inaddition, there were man y minor degradates, which were formed at low levels indiv idually but reached substantial amounts as groups. 2. Overview of Pesticide Usage As a new pesticide active ingredient, the actual usage of metrafenone is not known. The end
- use product Metrafenone 300 SC is proposed for use on grapes. Ground application is the proposed method of application. The label states, “do not apply directly to water, to areas where surface water is present, or to intertidal areas below the mean high water mark.” The chemical is to be applied at most 6 times per season at a maxi mum application rate of 0.3 lbs a.i./A ( Table 5 ). The label also states, “do not make more than 2 sequential applications of Metrafenone 300 SC fungicide before alternating to a labeled fungicide with a different mode of action.” Table 5. Metrafenone use and application information based on the proposed label for Metrafenone 300 SC

Use Max. Single App. Rate (lbs a.i./A) # of

App. / Season Seasonal Max.

Rate (lbs a.i./A) Minim umApp.

Interval (days) Grapes 0.300 6 1.80 14 days C. Receptors

1. Aquatic and T errestrial Effects The receptor is the biological entity that is exposed to the stressor (EPA, 1998). Based on the proposed uses for metrafenone, it is expected that the aquatic and terrestrial receptors will include freshwater fish and invertebrates, marine/estuarine fish and invertebrates,Page 19 of 114

aquatic plants, terrestrial plants, birds, mammals, and terrestrial invertebrates. Consistent with the process described in the Overview Document (EPA, 2004 ), this risk assessment uses a surrogate species approach in its evaluation of metrafenone. Toxicological data generated from surrogate test species, which are intended to be representative of broad taxonomic groups, are used to extrapolate to potential effects on a variety of species (receptors) included under the se taxonomic groupings. Acute and chronic toxicity data from studies submitted by pesticide registrants are used to evaluate the potential direct effects of metrafenone to the aquatic and terrestrial receptors identified in this section. This includes toxicity data on the technical grade active ingredient, an y major transformation products, and when available, formulated products (e.g. “Six
- Pack” studies). Table 6 provides a summary of the taxonomic groups and the surrogate species tested to help und erstand potential acute ecological effects of pesticides to these non
- target taxonomic groups. In addition, the table provides a preliminary overview of the potential acute toxicity

of metrafenone by

providing the acute toxicity classifications. Table 6 . Test Species Evaluated for Assessing Potential Ecological Effects of Metrafenone and the Associated Acute Toxicity Classification Taxonomic Group Surrogate Species Acute Toxicity Classification Birds 1 Mallard Duck ( Anas platyrhync hos ) Bobwhite Quail ( Colinus virginianus ) Passerine species Practically nontoxic Practically nontoxic No available study Mammals Laboratory rat (Rattus norvegicus) Laboratory mouse Practically non - toxic Practic ally non
- toxic Insects Honey bee ( Apis mellifera L. ) Practically non
- toxic Freshwater fish2 Bluegill sunfish ( Lepomis macrochirus ) Rainbow trout ( Oncorhynchus mykiss ) H ighly toxic H ighly toxic Freshwater invertebrates Water flea ( Daphnia magna ) At most, highly toxic Marine/estuarine fish Sheepshead minnow (Cyprinodon variegatus) H ighly toxic Marine/estuarine invertebrates My sid shrimp (Americamysis bahia) Eastern oyster ( Crassostrea virginica) Highly toxic Highly toxic Terrestrial plants 3 Monocots

– mo st sensitive species Dicots

– mo s t sensitive species No Classification

Aquatic plants and algae Duckweed ( Lemna gibba ) Cyanobacteria/blue
- green algae ( Anabaena flos

- aquae ) Marine diatom ( Skeletonema costatum ) Freshwater diatom (Navicula pellic ulosa ) Algae (Pseudokirchneriella subcapitata ; previously known as Selenastrum capricornutum ) No classification

1 Birds represent surrogates for terrestrial
- phase amphibians and reptiles. 2 Freshwater fish may be surrogates for aquat ic
- phase amphibians. 3 Normally four species of two families of monocots, of which one is corn; six species of at least four dicot families, of whic h one is soybeans.Page 20 of 114 2. Ecosystems Potentially at Risk The ecos ys tems at risk are often extensive in scope, an d as a result it may not be possible to identify

specific ecos ystems during the development of a baseline risk assessment. However, in general terms, terrestrial ecos ys tems potentially at risk could include the treated field and areas immediately adjacent to the treated field that may receive drift or runoff. Areas adjacent to the treated field could include cultivated fields, fencerows and hedgerows, meadows, fallow fields or grasslands, woodlands, riparian habitats, and other uncultivated areas. Aquatic ecos ys tems potentially at risk might include but are not necessarily limited to water bodies adjacent to, or down stream from, the treated field and might include impounded bodies such as ponds, lakes and reservoirs, or flowing waterways such as stream s or rivers. For uses in coastal areas, aquatic habitat also includes marine ecos ys tems, including estuaries.

D. Assessment Endpoints Assessment endpoints represent the actual environmental value that is to be protected, defined b y an ecological entity (spe cies, community , or other entity) and its attribute or characteristi cs (EPA, 1998). Generall y , the ecological entities may include the following: freshwater as well as marine/estuarine fish and invertebrates, aquatic and terrestrial plants, birds, reptile s, amphibians, mammals, and non
- target insects. For metrafenone: chronic risk to mammals is expected . The attributes for each of these entities may include growth, reproduction, and survival.

E. Conceptual Model A conceptual model provides a written description and visual representation of the predicted relationships between metrafenone residues, potential routes of exposure, and the predicted effects for the assessment endpoint. A conceptual model consists of two major components: risk hypothesis and a co nceptual diagram (EPA, 1998). 1. Risk Hypothesis For a pesticide to pose an ecological risk, it must reach ecological non
- target organisms (receptors) at biologically significant concentrations. An exposure pathway is the means by which a pesticide moves in the environment from the application site to non
- target organisms. The evaluation of the ecological exposure pathway s in this assessment includes an examination of the source and potential transport pathway s for metrafenone and the determination of exposure routes of non
- target species. Metrafenone, when used in accordance with the label, results in potential direct adverse effects upon the growth and reproduction of mammals. As a result, g iven the persistence of metraf enone, there is potential for indi rect effects to terrestrial and/or aquaticPage 21 of 114

organisms. 2. Conceptual Diagram The conceptual model diagram is a generic graphic depiction of the risk hypotheses identified in the previous section. It is assumed that metrafenone is capable of affecting expose d terrestrial and aquatic organisms if environmental concentrations are sufficientl y elevated as a result of proposed label uses. Through a preliminary process of examining fate and effects data, the risk hy potheses and conceptual model have been refined to reflect possible exposure pathway s and the organisms that are most relevant and applicable to this assessment ( Figure 2 ). If exposed at sufficient levels, mortality may occur, as well as sublethal effects. Direct effects on a taxonomic group may result in indirect effects (i.e., loss of habitat, food resources) to other taxonomic groups. This assessment will examine the potential for these effects to occur within the surrogate taxa with the intent to extrapolate to actual effects within the environment. In order for a chemical to pose an ecological risk, it must reach ecological receptors in biologicall y significant concentrations. An exposure pathway is the means by which a contaminant moves in the environment from a source to an ecological receptor . For this pathway to be complete, it must have a source, a release mechanism, an environmental transport medium for metrafenone and/or its transformation products, a point of exposure for ecological receptors, and a feasible route of exposure. The asses sment of these pathway s thus includes an examination of the sources and potential migration pathway s for constituents, and the determination of potential exposure routes. The conceptual model for both potential aquatic and terrestrial risk is shown in F igure 2
. Exposure routes shown in dashed lines are not quantitatively considered because the resulting exposures are expected to be very low when compared to the major routes of exposure. Exposure is expected to be dominated by runoff and spray

drift. Me trafenone exposure may also result from off

- site movement in runoff water and on metrafenone
- bearing soil particulates to adjacent fields (soil erosion). The moderate Koc ’s (Koc 1073 to 22517 L/kg
- oc) of metrafenone suggest that leaching to ground water/r echarge to surface water would not be a route of exposure. L ong - range transport of metrafenone in the gas phase is not considered a significant route of exposure. This screening
- level assessment for ground spray applications of metrafenone only considered dietary

exposure. Other routes of exposure that were not considered in the assessment are incidental soil ingestion exposure, inhalation exposure, dermal exposure, and drinking water exposure. These routes are not represented in the diagram ( Figure 2 ).Page 22 of 114

Figure 2. Conceptual Model Depicting Sources of Exposure from Metrafenone as well as Metrafenone Residues , Potential Receptors, and Adverse Effects from the Proposed Uses of Metrafenone on Grapes.

F. Analysis Plan The s tructure of this risk assessment is based on guidance contained in U.S. EPA’s Guidance for Ecological Risk Assessment (U.S. EPA, 1998) and is consistent with procedures and methodology outlined in the Overview Document (U.S. EPA, 2004). 1. Conclusions from P revious Risk Assessments There are no previous ecological risk assessments because this is the first registration petition for metrafenone for use on grapes in the United States. 2. Preliminary Identification of Data Gaps Review of the submitted studies indicated the following points: Stressor Metrafenone applied as foliar spray with ground equipment on grapes l

Source/ Transport Pathways Direct Deposition Spray Drift Runoff/ Erosion Leaching (Infiltration/ Percolation Source/ Exposure Me dia Terrestrial Food Residues (foliage, fruit, insects Upland

Foliage/Soil Riparian/

We tland Foli age/Soil Receiving

Wa ter Body/ Sediment Groundwater
Exposure Route Ingestion Direct contact/ Root Uptake Direct contact/

Root Uptake Gill/ Integument Uptake Receptors

At tribute Changes Terrestrial Vertebrates Birds, Mammals, Reptiles, Terrestrial Phase Amphibians Terrestrial Upland Plants

Individual Animals Reduced survivall Reduced growth Reduced reproduction Aquatic Invertebrates Aquatic Vertebrates We tland/ Riparian Plants

Individual Plants Seedling emergence Vegetative vigor Individual vertebrates and invertebrates Reduced survivall Reduced growth Reduced reproduction Plant population Reduced population grow th Aquatic Plants Uptake/ AdsorptionPage 23 of 114

Environmental Fate All but one of the environmental fate studies required to support the registration of metrafenone for use on grapes were submitted. In dependent Laboratory Validations for the methods submitted for analy sis of metrafenone in soi l and water remain a data gap. For a list of submitted environmental fate studies for metrafenone see Appendix F
. All of the environmental fate studies for the parent compound were de termined to be scientificall y valid and there fore results from all of the studies can be used to characterize the mobility

and rates of transformation of metrafenone. However, many of the metabolism studies have major uncertainties in the identification and pattern of formation and decline of transf ormation products. In all of the aquatic metabolism studies, between 57% and 65% of the applied radioactivity remains unidentified with incomplete characterization, and in two aerobic soil metabolism studies, 15% and 44% of the applied radioactivity

is un identified. This includes at least four major degradates that individually

reach levels of 11% to 35% of the applied. Other transformation products appear as groups of up to 15 components, in some cases characterized as each being <5% of the applied radi oactivity , but in other cases, some individual components make up 9% to 10% of the applied. Even when individual components can all be classified as minor degradates, these groups represent such a large portion of the applied radioactivity overall that th e possibility

that they may have some impact as a group cannot be precluded despite their lower individual levels. This is especially true given that the degradation pathway s suggest that groups of degradates may have a high degree of structural similarity and so may

have similar fate and effects behavior. Without information to adequatel y characterize the degradates, it may be necessary

to assume that they

are of equal toxicity

to the parents in order to quantify risks. In addition to the studies submitted by the registrant, EFED was provided with a Draft Assessment Report (DAR) on Metrafenone written by the United Kingdom. That assessment reports that the long dissipation time observed in field studies triggered a requirement for longer term field accumulation studies. Two years into those five year studies, results show that metrafenone appears to be accumulating, and that metrafenone residues have been detected as deep as 20
- 30 cm below the surface. These studies would provide useful information regarding the environmental fate of metrafenone and would assist in reducing uncertainties. Ecotoxicity The submitted ecotoxicity database is incomplete. The greatest amount of uncertainty in the assessment stems from aquatic studies which were largely based on total (both dissolved and undissolved) concentrations of test compound ; that is, the concentrations were measured without centrifugation even though precipitate was observed or test was conducted at the solubility limit of the metrafenone technical gra de active ingredient; the solubility limits of the metabolites are unknown . To reduce uncertainty the majority of the toxicity studies, which are considered supplemental, and cannot be used in a quantitative risk estimation would need to be redone; especially thosePage 24 of 114

where mortality

or sublethal effects were observed. These aquatic studies are specified below. For a list of submitted ecological effects studies for metrafenone see Appendix G
. The following studies are considered data needs: Aquatic studies Given the freshwater fish studies on metrafenone technical grade active ingredient and assuming that the concentrations in the environment reach the solubility limit, the effect of the compound is likely to be low. However, according to model estimated EECs (which include metrafenone and metrafenone residue scenarios: 0.00153
- 0.02 mg/L ), levels of metrafenone (TGAI, TEP) 3 at the solubility limit (0.2
- 0.5 mg/L at 12 o C) and metrafenone metabolites at the tested concentrations are not expected to occur in the environment given the proposed grape use. Therefore, acute risk to freshwater fish and aquatic
- phase amphibians is not expected as a result of metrafenone use on grapes. In addition, although the EU/UK formulation

– with which the submitted studies we re conducted

– closel y matches the U.S. formulation ( i.e. , BAS 560 03F) it is still not its equivalent. Therefore, the effect of the U.S. formulated product on freshwater fish and aquatic
- phase amphibians is not known. T o reduce uncertainty

in characteri zing risk, which is currentl y based on total concentrations, the freshwater fish studies on bluegill sunfish ( Lepomis macrochirus ) are requested to make same species comparisons for acute and chronic values. Bluegill was chosen over the rainbow trout due t o greater sensitivity (on an acute basis) of the bluegill to the TGAI relative to the trout. Since the acute marine/estuarine fish study is acceptable and given the above two studies, the acute to chronic ratio can be utilized to estimate marine/estuarine chronic endpoints, negating the need to fill this data gap. Special emphasis must be placed on centrifuging the test samples prior to anal yt ical determination of the test compound.

 Acute: Freshwater fish toxicity (96
- hour L C 50 for Lepomis macrochirus ) (8 50.1075; 72
- 1), TGAI  Chronic: Fish earl y- life stage (freshwater: Lepomis macrochirus ) (850.1400; 72
- 4), TGAI Although acute freshwater invertebrate studies were based on total concentrations, no effects were observed with the TGAI, negating the need to r equest additional data. However, a chronic freshwater invertebrate data gap still exists since the two reviewed studies were deemed invalid.

 Chronic: Aquatic invertebrate life cycle (freshwater: Daphnia magna ) (850.1300; 72
- 4), TGAI

3 TGAI: technical grade active ingredient; TEP: typical end
- use product (formulation)Page 25 of 114

Effects were observe d in both acute marine/estuarine invertebrate studies with the TGAI on the eastern o ys ter ( Crassostrea viginica ) and saltwater m ys id ( Americamysis bahia ) but the endpoints are based on total concentrations. Therefore, should concentrations in the environme nt reach the solubility limit, the acute risk to marine/estuarine invertebrates may be expected
. However, according to the model estimated EECs (0.00153
- 0.02 mg/L, which includes metrafenone and total metrafenone residue scenarios), levels of metrafenone at the solubility limit are not expected to occur in the environment given the proposed grape use. Given these studies and assuming that metrafenone concentrations in the environment are not likely to reach the solubility

limit, the acute risk to marine/e stuarine invertebrates is not expected. However, to reduce uncertainty in characterizing risk, either study is requested to be redone with special emphasis on centrifuging the test samples prior to anal yt ical determination of the test compound.

 Acute: Marine/estuarine invertebrate either Crassostrea virginica (850.1025; 72
- 3) or Americamysis bahia (850.1035; 72
- 3), TGAI A non
- guideline chronic midge study ( Chironomus riparius ) with metrafenone technical (97.1%) was deemed invalid on the basis of low negative control emergence. Therefore, a chronic freshwater invertebrate whole sediment study is requested. A protocol should be submitted for approval prior to study initiation. The protocol should include spiked sediment. The whole sediment study is requeste d because metrafenone has a high logKow value (4.3 at 25 o C, pH 4) and a high aerobic soil half life (> 4 months), which indicates that the compound may

partition to sediment and persist.

 Chironomus dilutus (freshwater) using TGAI. Consult EPA Test Method 100.5 Life
- cycle Test for Measuring the Effects of Sediment Associated Contaminants on Chironomus dilutus (formerl y Chironomus tentans ) and OECD Guideline 218 Sediment
- Water Chironomid Toxicity Test Using Spiked Sediment Non
- target aquatic plant studies w ere also based on total concentrations leading to uncertainty in exposure concentrations and thus endpoint values. H ad valid endpoints ( i.e. , those based on dissolved concentrations) been determined using these studies, they would likely

be greater than th e highest model predicted concentration in the environment, which implies that risk to vascular and non
- vascular species is not expected as a result of metrafenone use on grapes. However, w ithout centrifugation, the amount of chemical that is freel y dissol ved and bioavailable cannot accurately be determined
. Therefore, vascular and non
- vascular aquatic plant studies are requested with special emphasis placed on centrifuging the test samples prior to anal yt ical determination of the test compound. In addition , cyanobacteria yielded no effects given total concentrations and does not need to be redone.

 Aquatic vascular plant growth ( Lemna spp.), Tier II (850.4400), TGAI  Aquatic non
- vascular plant growth, Tier II (850.5400), TGAIPage 26 of 114

Terrestrial Studies An avian acute oral toxicity test in passerine species is required. Passerines are the most common birds (in terms of numbers and number of species) in the United States. Many utilize agricultural fields, forests, residential areas and surrounding areas, an d, therefore, have the potential to be exposed to pesticides used in agricultural, forest, and residential settings. It is likely

that, for the requested use patterns, passerines are more likely to be exposed to metrafenone than upland game species and waterfowl. Passerines are smaller and have a higher energy requirement than larger
- sized birds. As such, passerines may be more sensitive than other birds.

 Passerine bird toxicity study (EPA approved protocol is required prior to study initiation): Avian acute oral toxicity test (850.2100, 71
- 1), TGAI Formulated Product Testing The available formulation product studies were conducted using three different UK/EU formulated products ( i.e. , BAS 560 00F, BAS 560 01F, and BAS 560 02F), one of which (BAS 560 00F) closel y matches the U.S. formulation ( i.e. , BAS 560 03F). Formulation studies in this assessment are based on BAS 560 00F because data on the U.S. formulation were not submitted. In order to eliminate uncertainty in effects characterization of formulated products used within the U.S. on given taxa, future registrant submitted studies should be based on the U.S. formulation. At this time the effect of the U.S. formulation on given taxa is not known , however, greater toxicity of the EU/UK formulation on the honey bee relative to the TGAI was observed
. Similarly , data submitted for terrestrial plants is based on the EU/UK formulation. As a result, the following studies are requested:

 Honey

bee acute contact toxicity (850.3020, 141
- 1), TEP  Seedling emergenc e, Tier II (850.4225, 123
- 1), TEP  Vegetative vigor, Tier II (850.4250, 123
- 1), TEP

3. Measures of Exposure and Effects EFED uses a tiered s ys tem of pesticide exposure modeling to assess ecological risk following a registered application of that pesticide. This tiered sy stem is designed to minimize the amount of anal ys is which is required to register any given chemical. Each of the tiers is designed to screen out pesticides by requiring higher, more complex levels of investigation onl y for those that have n ot passed the next lower tier. Each tier screens out a percentage of pesticides from having to undergo a more rigorous review prior to registration or re - evaluation
.Page 27 of 114 a. Aquatic Exposure Models Tier II PRZM and EXAMS 4 simulation models were used to estim ate the exposure concentrations of metrafenone in surface water for the proposed use on grapes. The results are presented in Appendix B. The data used as input parameters come solel y from the environmental fate studies and proposed product label submitted by the petitioner to support in the United States the registration of metrafenone as a new pesticide
- active ingredient for grapes. KABAM ( KOW (based) A quatic B io A ccumulation M odel) v.1.0 is used to estimate potential bioaccumulation of hydrophobic organ ic pesticides such as metrafenone (log Kow > 4) in freshwater aquatic food webs and subsequent risks to mammals and birds via consumption of contaminated aquatic prey . The bioaccumulation portion of KABAM is based upon work b y Arnot and Gobas (2004) who parameterized a bioaccumulation model based on PCBs and some pesticides (e.g., lindane, DDT) in freshwater aquatic ecos ys tems. KABAM relies on a chemical's octanol
- water partition coefficient (KOW) to estimate uptake and elimination constants through respiration and diet of organisms in different trophic levels. Pesticide tissue residues are calculated for different levels of an aquatic food web. The model then uses pesticide tissue concentrations in aquatic animals to estimate dose
- and dietary
- based exposur es and associated risks to mammals and birds consuming aquatic organisms, using an approach that is similar to the T
- REX model (USEPA 2008). KABAM incorporates 7 trophic levels to describe bioaccumulation of a pesticide in a model aquatic food web: phy t oplankton, zooplankton (e.g., Daphnia sp.), benthic invertebrates (e.g., Chironomus sp., crayfish), filter feeders (e.g., mussels, clams), small fish (e.g., young of the year), medium sized fish (e.g., adult bluegill), and larger upper
trophic level fish ( e.g., largemouth bass). Metrafenone concentrations in organisms of the aquatic trophic levels listed above were used to estimate acute and chronic exposures of piscivorous mammals and birds consuming fish. Applicable and available acute and chronic toxic ity data on metrafenone (mammals and birds) were used to calculate risk quotients for estimated exposures due to bioaccumulation of metrafenone in an aquatic ecosy stem. b. Terrestrial Exposure Models T - REX Model The focus of terrestrial wildlife exposure estimates is for birds (also acting as surrogate for reptiles and terrestrial
- phase amphibians) and mammals with an exposure route emphasis on uptake through the diet. The residues in or on potential dietary sources for mammals and birds (e.g., vegetatio n, insects, and seeds) were estimated using the Tier I

4 PRZM 3.1.2.2 (5/16/05) and EXAMS 2.98.04(4/25/04) were used rather than GENEEC2 (4/25/04) in anticipation of toxicity concerns for aquatic organisms.Page 28 of 114

model T
- REX (Version 1.4.1, 2008). In this Tier I assessment, it was assumed that organisms are exposed to one active ingredient in a given exposure scenario. In all screening
- level assessments, the organisms are assumed to consume 100% of their diet as one food type and one food source . The T
- REX output is presented in the Risk Characterization section of this document as well as an example in Appendix C
. The approach used to estimate exposure of terrestrial animals to metrafenone was based on potential foliar applications of metrafenone. Upper
- bound exposure levels were calculated for spray

applications of metrafenone using maximum proposed application rates for one application for the proposed u ses. The exposure estimates are based on a database of pesticide residues on wildlife food sources associated with specified application rates (Kenaga, 1972; Fletcher et al., 1994). Essentially , for a single application, there is a linear relationship betw een the amount of pesticide applied and the amount of pesticide residue present on a given food item. Food item residue levels are then linearl y adjusted based on application rate. The upper
- bound estimates are used to estimate risks since these values represent the high
- end exposure that may be encountered for terrestrial species that consume food items that have received label
- specified pesticide application. Although these represent higher
- end estimates, they do not represent the highest possible expos ure estimates. T
- REX is a simulation model that, in addition to incorporating the relationship between application rate and food item residue concentrations, accounts for pesticide degradation in the estimation of terrestrial EECs. T
- REX calculates pest icide residues on each type of food item on a daily

interval for one year. A first
- order decay function is used to calculate the residue concentration at each day based on the concentrations present from both initial and all subsequent applications. The d ecay rate is dependent on the foliar dissipation half

- life. The food item concentration on any given day

is the sum of all residues up to that day , taking into account the first
- order degradation. The initial application occurs on day 0 (t=0) and the model runs for 365 day s. Over the 365
- day run, the highest residue concentration is the measure of exposure (EEC) used to calculate risk quotients (RQs). The foliar dissipation half
- life and residue decline studies can be important in estimating exposure beca

use they essentially

determine how long the pesticide remains in or on food items after application. In many cases, neither empirically determined foliar dissipation nor residue decline half

- life (with a day

0 residue) values are available, in which case the default value of 35 day s is used (Willis and McDowell, 1987). That was the case for this assessment. TERRPLANT Model The TerrPlant (Ver.1.2.2) model is used to predict EECs from terrestrial uses for terrestrial plants located in dry and semi
- aquatic areas adjacent to the treated field or treated water body. TerrPlant assumes 100% efficiency in ground and aerial applications. A semi
- aquatic area (wetland) is defined as a low
- lying area of terrestrial habitat that is wet but may

dry up at times through out the year. TerrPlant incorporates two similarPage 29 of 114

conceptual models for depicting dry and semi
- aquatic areas of terrestrial habitats. For both models, a non
- target area is adjacent to the target area. Pesticide exposures to plants in the non
- target area are estimated to receive runoff and spray drift from the target area. For a dry area adjacent to the treatment area, runoff exposure is estimated as sheet runoff. Sheet runoff is the amount of pesticide in water that runs off of the soil surface of a targ et area of land which is equal in size to the non
- target area (1:1 ratio of areas). In the sheet runoff scenario, the treated area generating runoff is assumed to drain into an area with equal size containing seedlings, resulting in 1, 2, or 5% of the app lication rate being deposited. For semi
- aquatic areas, runoff exposure is estimated as channel runoff. Channel runoff is the amount of pesticide that runs off of a target area 10 times the size of the non
- target area (10:1 ratio of areas). In the channe l runoff scenario, a ten
- to - one ratio of watershed area to receiving area results in 10, 20, or 50% of the application rate being deposited on soil with emerging or emerged seedlings. The magnitude of runoff is assumed to be dependent on the water solubil ity of the pesticide active ingredient. For pesticides with a solubility of <10, 10 to 100, or >100 ppm, runoff fractions of 0.01, 0.02 or 0.05 respectively

are selected b y the model user. Exposures through runoff and spray drift are then compared to measures of survival and growth (e.g. effects to seedling emergence and vegetative vigor) to develop RQ values. The model compares the combined deposition estimates from runoff and spray drift to adverse effect levels measured in seedling emergence studies. In addition, RQs are derived for plants with consideration for spray drift exposures. For monocots and for dicots, TerrPlant compares estimated spray drift deposition, without a runoff exposure component, to the more sensitive measure of effect, either seedling emergence or vegetative vigor (USEPA 2005 ). Table 7 summarizes the measures of ecological effects and exposure used to assess ecological risk following exposure to metrafenone with the proposed uses.

Table 7 . Measures of Ecological Effec ts and Exposure for Metrafenone

Assessment Endpoint Surrogate Species and Me asures of Ecological Effect 1,2 Me asures of Exposure
Birds 3 Survival Bobwhite Quail acute oral LD 50 , subacute dietary LC 50 Mallard Duck acute oral LD 50 , subacute dietary LC 50 Upper bound residues on food items (foliar) Reproduction and growth Bobwhite Quail reproduction NOAEC/LOAEC Mammals Survival Laboratory rat acute oral LD 50 Laboratory mouse acute oral LD 50 Reproduction and growth Laboratory rat reproduction NOAEL/LOAELPage 30 of 114

Table 7 . Measures of Ecological Effec ts and Exposure for Metrafenone

Assessment Endpoint Surrogate Species and Me asures of Ecological Effect 1,2 Me asures of Exposure
Freshwater fish4 Survival Rainbow trout 96
- hr LC 50 Bluegill sunfish 96
- hr LC 50 Peak EEC 5 Reproduction and growth Fathead minnow NOAEC/LOAEC 60
- day average EEC 5 Freshwater invertebrates Survival Water flea 48
- hr EC 50 Peak EEC 5 Reproduction and growth No acceptable study available 21
- day average EEC 5 Marine/estuarine fish Survival Sheepshead minnow 96
- hr LC 50 Peak EEC 5 Reproduction and growth No study available 60
- day average EEC 5 Marine/estuarine invertebrates Survival Eastern oyster 96
- hr EC 50 Saltwater mysid 96
- hr LC 50 Peak EEC 5 Reproduction and growth Saltwater mysid NOAEC/LOAEC 21
- day average EEC 5 Terrestrial plants 6 Survival and growth Monocot Seedling emergence EC 25 , NOAEC or EC 05 Monocot Vegetative Vigor EC 25 , NOAEC or EC 05 Dicot Seedling emergence EC 25 , NOAEC or EC 05 Dicot Vegetative Vigor EC 25 , NOAEC or EC 05 Estimates of runoff and spray drift to non
- target areas

Insects Survival Honey bee acute contact 48
- hr LD 50 Maximum application rate Aquatic plants and algae Survival an d growth Duckweed 7
- day EC 50 , NOAEC Cyanobacteria 96
- hr EC 50 , NOAEC Marine diatom 96
- hr EC 50 , NOAEC Freshwater diatom 96
- hr EC 50 , NOAEC Green algae 96
- hr EC 50 , NOAEC Algae 72
- hr EC 50 , NOAEC Green algae 72
- hr EC 50 , NOAEC Peak EEC 5

1 LD 50 = Lethal dose to 5 0% of the test population; NOAEC = No observed adverse effect concentration; LOAEC = Lowest observed adverse effect concentration; LC 50 = Lethal concentration to 50% of the test population; EC 50 /EC 25 = Effect concentration to 50%/25% of the test population
. 2 If species listed in this table represent most commonly encountered species from registrant
- submitted studies, risk assessment guidance indicates most sensitive species tested within taxonomic group are to be used for baseline risk assessments. 3 Birds represent surrogates for amphibians (terrestrial phase) and reptiles. 4 Freshwater fish may be surrogates for amphibians (aquatic phase). 5 One in 10
- year return frequency. 6 Four species of two families of monocots
- one is corn, six species of at least four dicot families, of which one is soybeans.Page 31 of 114

III. Analysis

A. Use Characterization The proposed end
- use product is “Metrafenone 300 SC” (EPA Reg. No. 7969
- XXX), a suspension concentrate containing 25.2% (3
- bromo
- 6
- methoxy
- 2
- methylphenyl)(2,3,4
- trimethoxy
- 6
- methylphenyl)methanone (metrafenone) at a concentration of 2.5 lbs metrafenone per gallon. The product is claimed to provide “optimum disease control when applied in a regularly scheduled protective fungicide program and when used in a spray program th at rotates fungicides with different modes of action.” The product is intended to control powdery mildew of grapes. Ground application is the proposed method of application. The label states, “do not apply directly to water, to areas where surface wate r is present, or to intertidal areas below the mean high water mark.” The chemical is to be applied at most 6 times per season at a maximum application rate of 0.3 lbs a.i./A (Table 5 ). The label also states, “do not make more than 2 sequential applicatio ns of Metrafenone 300 SC fungicide before alternating to a labeled fungicide with a different mode of action.”

B. Exposure Characterization

1. Environmental Fate and Transport Summary Metrafenone is a new chemical of the benzophenone class that is expected t o be slightly mobile. Its major routes of degradation are aqueous photolysis and aquatic metabolism, in both aerobic and anaerobic conditions. Soil metabolism is slow, with laboratory half
lives of 6 months to a year and accumulation over two years obser ved in field studies. In aquatic environments, the measured photoly sis half
- life was 6.4 day s and metabolism in both aerobic and anaerobic occurred with half
- lives of one to four weeks. Soil photolysis and anaerobic aquatic metabolism of metrafenone led to one major degradate, CL377160 [Methanone, (3
- bromo
- 6
- methoxy
- 2
- methylphenyl)(3
- hydrox y2,4
- dimethoxy
- 6
- methylphenyl)
- ]

. , and anaerobic aquatic metabolism also led to six other major degradates, but all were either unidentified or only tentativel y ident ified. In addition, there were many minor degradates, which were formed at low levels individually

but reached substantial amounts as groups. Tier II aquatic exposure modeling was conducted for parent metrafenone and metrafenone residues (metrafenone+ extractable residues) (Table 1 1). This modeling approach was used to address uncertainties associated with identification of metrafenone residues in soil and sediment. The highest aquatic EECs for metrafenone were 11.70 μg/L for the daily peak, 8.82 μg/L for the 21 day average, and 6.21 μg/L for the 60 day average. The highest aquatic EECs for metrafenone were 20.22 μg/L for the daily peak, 17.67 μg/L for the 21 day average, and 16.98 μg/L for the 60 day average.Page 32 of 114

No moni toring data are available to compare with model estimates. Bioaccumulation modeling was conducted because metrafenone has a log octanol:water coefficient > 4. Maximum residue concentrations in fish are expected to range from 17,636 to 19,586 μg/kg
- ww. Persistence Metrafenone biodegrades slowly in terrestrial environments. In laboratory studies in a variety of soils, aerobic soil metabolism linear half
- lives ranged from 178 to 365 day s. In four of the eight soils tested, data collection extended long enough to determine an empirical DT 50 , of 124 to 188 day s in two silt loam soils and 272 to 362 day s in a clay loam and sandy loam soil. In these two soils, metabolism appeared to slow after 272 day s. No data are available for anaerobic soil metabolism rates. Photoly sis on soil was observed in laboratory

studies to occur with a linear half
- life of 31 day s. In aquatic environments, metrafenone biodegrades in weeks to months in both aerobic and anaerobic conditions (linear half
- lives of 24
- 27 day s and 1 8
- 22 day s, respectively). Considering a

biotic degradation, metrafenone is pho toly zed in water (half

- life of 6 .4 day s), but is stable to hydroly sis at pH values from 4 to 9. Degradation Products The only positivel y identified major degradate of metrafenone was CL 377160 [Methanone, (3
- bromo
- 6
- methoxy
- 2
- methylphen yl)(3
- hydrox y- 2,4
- dimethoxy
- 6
- methylphen yl )
- ]. CL377160 was formed through soil photolysis at up to 18.9% AR and through anaerobic aquatic metabolism at up to 10.8% AR in the total sy stem. It was also formed as a minor degradate through aquatic photoly sis and aerobic aquatic metabolism. A compilation of identified degradation products are shown in Appendix A
. In one anaerobic aquatic metabolism study , another six degradates were formed at >9 %, but these were either unidentified or onl y tentatively identified. These included TN (tentatively

identified as a lactone compound; maximum 3.3%, 26.9% and 28.0% in the water layer, sediment and total sy stem, respectively), MB (tentativel y identified a s a hydrox yl ation product of TN; maximum 1.1%, 11.6% and 11.7% in the water layer, sediment and total sy stem, respectivel y), and four unidentified degradates formed in the total sy stem at 9.3% to 13% AR. Carbon dioxide was also a major degradate, formed through aquatic photolysis at up to 25% AR and through all other measured processes as a minor degradate. Most processes also resulted in formation of a substantial amount of minor degradates, some individually

measured and identified, but most not. Although all of these degradates were present at less than 10%, and some at very low levels, they

still may be of exposure concern because of the large overall amounts. In some cases minor degradates, mostly

unidentified, make up more than 50% of the applied radioactivity in a single sampling event. In addition, based on the structure of the parent compound andPage 33 of 114

the proposed degradation pathway s, man y of the minor degradates may have a high degree of structural similarity to each other and/or the parent and s o may have cumulative effects. Mobility Batch equilibrium data on metrafenone suggest that the compound will sorb to organic surfaces and would be considered “slightly mobile” according to the FAO classification scheme (organic carbon partition coefficients range from 1,073 to 2,792 ml/g
- oc ). Also according to FAO classification, metrafenone’s solubility in water of 0.447 mg/L is considered “slightl y soluble.” It showed low volatility from soil and water with <0.5% volatilization in any

laboratory

study , consistent with the vapor pressure of 1.15 x 10 - 6 mmHg . Therefore, dissipation in the environment is expected to occur predominantly via runoff of suspended soil and sediments to which metrafenone is adsorbed. Based on terrestrial field dissipation stu dies in the UK , metrafenone was detected at a soil depth of 20
- 30 cm after 2 years. In aquatic s ys tems, partitioning of metrafenone to sediment occurred rapidly . In one anaerobic s ys tem, half of the applied metrafenone was detected in sediment on the fi rst day , and in three other s ystems (one anaerobic, two aerobic), at least 50% of the parent compound had partitioned to sediment within three to seven day s. Including degradates, partitioning was rapid in anaerobic s ys tems but slower in aerobic s ys tems. Intwo anaerobic aquatic metabolism studies, more than half of the applied radioactivity (AR) was found in sediment within one week and radioactivity in the water layer was down to <5% AR in two to six weeks. However, in aerobic aquatic metabolism studie s in two sy stems, from 8% to 28% AR remained in the water layer at study termination (100 day s). Field Dissipation Studies Field dissipation studies were conducted on bare plots in California (CA), Washington (WA), Ontario (ON), and Florida (FL). The f irst
- order dissipation half
- life for metrafenone in surface soils (0
- 7.5 cm) was 144 day s (DT 50 14
- 30 day s; DT 90 272
- 360 day s) in CA, 161.2 day s (DT 50 181
- 269 day s; DT 90 540
- 900 day s) in WA, 210 day s (DT 50 59
- 272 day s; DT 90 598
- 710 day s) in ON, and 1 61 day s (DT 50 14
- 30 day s; DT 90 360
- 451 day s) in FL. No degradation products were detected above the limit of quantification (LOQ) in the field dissipation studies. The reference degradation product in the field study was CL 377160. Degradation was not a clear route of metrafenone dissipation in field studies because of the lack of detectable degradation products in soil. L eaching is possible route of dissipation. There were sporadic detections of metrafenone with soil depth in the Florida study with max imum detection depth of 15
- 30 cm, Ontario study with maximum detection depth of 60
- 75 cm, Washington study

with a maximum depth depth of 7.5
- 15 cm, and California study withPage 34 of 114

a maximum detection depth of 15
- 30 cm. The field studies were not designed to as sess runoff and volatilization of metrafenone residues. Bioaccumulation in Fish Bluegill sunfish exposed to metrafenone, at 5 and 50 μg/L, accumulated metrafenone residues during a 28 day

accumulation period. After the accumulation phase, the fish w ere transferred to metrafenone
- free water for a 14 day depuration phase. For the bromophen yllabeled metrafenone, lipid normalized bioconcentration factors (BCFs) ranged 140 to 460 in whole fish. For trimethox ybenzene labeled metrafenone, lipid normalize d bioconcentration factors (BCFs) ranged 490 to 530 in whole fish. The lipid normalized BCF range indicates that metrafenone is not expected to accumulate in tissues of aquatic organisms. Major bioaccumulated residues (>10% of TRR) were identified as [(3
- B romo - 6
- methoxy
- 2
- methylphen yl )(4
- hydroxy
- 2,3
- dimethoxy
- 6
- ethylphen yl )methanone (CL434223), CL1500699 (3
- bromo
- 6
- methoxy
- 2
- methylphen yl )[4
- (beta
- D
- gluco p yr an uronosyloxy)
- 2,3
- dimethoxy
- 6
- methy phenyl]
- methanone), and CL377160. These degradation products were detected in whole fish, viscera, fillet, and in the exposure water. The bioaccumulation rate at 90% steady
- state of total radioactive residue and metrafenone ranged from 1.3 to 1.8 day s and 1.8 to 2.1 day s, respectively . The 95% depuration rate of total radioactive residue and metrafenone ranged from 1.8 to 2.3 day s and 1.8 to 2.1 days, respectively
. 2. Measures of Aquatic Exposure
a. Aquatic Exposure Modeling The estimated environmental concentration s (EEC s ) reported in the assessment were calculated using the Tier II model for surface water (PRZM/EXAMS). S ample inputs and outputs of the model are presented in Appendix B. PRZM (v3.12.2, May

2005) and EXAMS (v2.98.4.6, April 2005) are screening simulation models coupled with the input shell pe5.pl (Aug 2007) to generate dail y exposures and 1
- in
- 10 year EECs of metrafenone and total metrafenone residues that may occur in surface water bodies adjacent to application sites receiving metrafenone residues through runoff and spray

drift for specific scenarios. PRZM simulates pesticide application, movement and transformation on an agricultural field and the resultant pesticide loadings to a receiving water body via runoff, erosion and spray drift. EXAMS simulates the fate of the pesticide and resulting c oncentrations in the water body . The standard scenario used for ecological pesticide assessments assumes application to a 10
- hectare agricultural field that drains into an adjacent 1
- hectare water body, 2
- meters deep (20,000 m 3 volume) with no outlet. PRZM/EXAMS was used to estimate screening
- level exposure of aquatic organisms to metrafenone residues. The measure of exposure for aquatic species is the 1
- in
- 10 year return peak or rolling mean concentration. The 1
- in
- 10 ye ar peak is used for estimating ac ute exposures of direct effects to aquatic organisms as well as indirect effects. The 1
- in
- 10
- ye ar 60
- day mean concentration is used for assessing chronic exposure. The 1
- in
- 10 year 21
- day mean concentration is used for assessingPage 35 of 114

chronic exposures to aquat ic invertebrates. Input Parameters The appropriate input parameters were selected from the phy sical/chemical properties and environmental fate data submitted by the petitioner to support registration of metrafenone. Input parameters were selected in acc ordance with US EPA
- OPP EFED water model parameter selection guidelines, Guidance for Selecting Input Parameters in Modeling the Environmental Fate and Transport of Pesticides, Version 2.1 , November 10, 2009 . Expanded information about the models, selection of input parameters and scenarios can be obtained from http://www.epa.gov /oppefed1/models/water/index.htm. The use input parameters were selected from label for the end
- use product “Metrafenone 300 SC.” The phy sical
- chemical properties and environmental fate input parameters were obtained from studies submitted and reviewed by the Agency
. Total Residues Modeling Input Parameters Calculation of total residue half
- lives for m etrafenone are based on the concentration (expressed as percent of applied radioactivity) of extractable residues ( Table 8 ). Extractable residues include metrafenone, CL 377160, tentatively identified compounds, and unidentified compounds (Appendix A ). Table 8. Total Extractable Metrafenone Residue Half - lives from Laboratory Degradation Studies Study Type MRID 1 Half - life (days) Environmental

Matrix Extractable Residues Aqueous Photolysis
- 23 27 Total Mass Balance
- VOC

– CO 2 Soil Photolysis
- 24 47.8 Acetonitrile, acetonitrile:0.2NHCl, 0.5 N NaOH Aerobic Soil
- 27 169.1 sandy loam soil Acetonitrile, acetonitrile:acetone, acetonitrile:water Aerobic Soil
- 26 210.0 clay loam soil Acetone, methanol:water Aerobic Soil
- 25 277.2 silty loam soil Acetone, methanol :water, acetonitrile:0.5NHCl Aerobic Soil
- 27 277.3 clay loam soil Acetonitrile, acetonitrile:acetone, acetonitrile:water Aerobic Soil
- 27 301.4 silt loam soil Acetonitrile, acetonitrile:acetone, acetonitrile:water Aerobic Soil
- 26 315.1 sandy loam soil Acetone, methanol:water Aerobic Soil
- 27 330.1 silt loam so il Acetonitrile, acetonitrile:acetone, acetonitrile:water Aerobic Soil
- 26 364.8 loamy sand soil Acetone, methanol:water Anaerobic Aquatic
- 29 182.0 DI water - silty clay loam Water + Acetone, methanol acetic acid, acetonitrile, 0.5N

NaOH:acetonitrile, ammonium hydroxide:acetonitrile
Anaerobic Aquatic
- 31 577.6 pond
- sandy loam Water + acetone:acetonitrile, acetonitrile:formic acid, acetonitrile;water formic acid, acetonitrile:water:triethylamine, acetonitrile:0.05 M sodium phosphate dibasic, 0.5N ammonium hydroxide Aerobic Aquatic
- 30 91.2 river
- loam Water + acetone, methanol:acetic acid, methylene chloride, acetonitrile:0.5N NaOH Aerobic Aquatic
- 30 123.8 pond
- sand Total Mass Balance
- VOC

– CO 2 1
- Prefix MRID number is 472674
- Surface water Scenarios used to run PRZM and EXAMS (Tier II) for the proposed use are shown inPage 36 of 114

Table 9 . Input parameters for modeling in Tier II are shown in Table 10
. Table 9. Scenarios used to estimate Metrafenone concentrations in surface water. Agricultural Comm odity Crop Scenario Me t File Scenario Characterization Grapes NY

CA W14860.dvf W93193.dvf Standard Scenarios for assessing pesticides use on

grapes Table 10. PRZM/EXAMS Input Parameters for Metrafenone and Total Extractable Metrafenone Residues PARAME TER Me trafenone Total Extractable Me trafenone Residues COMMENT SOURCE Application Rate per Event Lb a.i./A (kg a.i./ha) 0.3 lb a.i./A 0.3 lb a.i./A Metrafenone 300 SC Label No. of Applications (Interval) 6 (14 day) 6 (14 day) Metrafenone 300 SC Label CAM (Chemical App. Method) 2 2 Broadcast spray Metrafenone 300 SC Label Depth of Incorporation 0 0 Default Spray Drift Fraction / Application Efficiency 0.01 / 0.99 0.01 / 0.99 Assume ground spray. EFED Input Guidance Aerobic Soil Metabolism t 1/ 2 303 days 313 days Upper 90 th percentile of the mean half

- life (n=8) MRID 47267425

MRID 47267426 MRID 47267427 Aerobic Aquatic Degradation t 1/ 2 28.2 days 158 days Upper 90 th percentile of the mean half

- life (n=2) MRID 47267430 Anaerobic Aquatic Degradati on t 1/ 2 25.3 days 989 days Upper 90 th percentile of the mean half

- life (n=2) MRID 47267429

MRID 47267431 Aqueous Photolysis t 1/ 2 6.4 days 27.0 days Corrected for dark MRID 47267423 Hydroly sis t 1/ 2 0 days 0 days Stable MRID 47267422 Soil Partition Coeff icient (Koc ) 2188 mL/g oc 2188 mL/g oc Average Koc MRID 47267420 Molecular Weight 409 g/mole 409 g/mole MRID 47267423 Water Solubility @ 25°C 0.474 mg/L 0.474 mg/L MRID 47267423 Vapor Pressure 1.15 x 10 - 6 mmHg 1.15 x 10 - 6 mmHg EPA Fact Sheet (9/06)Page 37 of 114

Tier II
- PRZM/EXAMS Tier II estimated environmental concentrations for metrafenone and total metrafenone residues are shown in Table 11
. Table 11. Estimated Exposure Concentrations for Metrafenone and Total Metrafenone Residues from Surface Water. Con centrations are in μg/L (ppb) Agricultural Comm odity/Scenario 1 - in - 10 yr Peak 1 - in - 10 yr 21 - Day Average 1 - in - 10 yr 60 - Day Average Me trafenone NY Grapes 11.70 8.82 6.21 CA Grapes 1.53 1.10 0.75 Total Metrafenone Residues * NY Grapes 20.22 17.67 16.9 8 CA Grapes 2.25 1.89 1.58 *P arent metrafenone + identified and unidentified extractable residues

b. Aquatic Exposure Monitoring and Field Data Monitoring data for metrafenone in surface water and ground water are not available in the United States o r Europe.

c. Aquatic Bioaccumulation Assessment
Available data on the octanol
- water partition coefficient (Kow) for metrafenone indicates that this pesticide may

accumulate in aquatic food webs. Because the Log Kow is > 4.0 , KABAM v.1.0 was used to es timate concentrations of metrafenone in tissues of aquatic organisms resulting from bioaccumulation. Input parameters are provided in Table 12 and e stimated concentrations of metrafenone in fish are provided in Table 13
. Sample KABAM output is provided in Appendix D
.Page 38 of 114

Table 12 . Input Param eters and Chemical Characteristics of Metrafenone Used in KABAM Characteristic Value Comments Log KOW 4.3

KOW 19953
KOC (L/kg OC) 2188 Input value used in PRZM/EXAMS to derive EECs.

Time to steady stat e (T S ; days) 8 This value is calculated automatically from the Log KOW value entered above. Pore water EEC (μg/L) 16. 8 Value generated by PRZM/EXAMS benthic file for New York Grapes scenario for metrafenone total residue and high runoff scenario . PRZM/EX AM S EEC represents the freely dissolved concentration of the pesticide in the pore water of the sediment. The appropriate averaging period of the EEC is dependent on the specific pesticide being modeled and is based on the time it takes for the chemical t o reach steady state. 21
- day average concentration ( EEC ) wa s used as averaging period closest to the time to steady state calculated above
.

Water Column EEC (μg/L) 17. 7 Value generated by PRZM/EXAMS water column file for New York Grapes scenario for metra fenone total residue and high runoff scenario . PRZM/EXAMS EEC represents the freely dissolved concentration of the p esticide in the water column. 21
- day average concentration (EEC) wa s used as averaging period closest to the time to steady state calculate d above (as discussed above for pore water).

Table 13 . Estimated Concentrations of Me trafenone in Fish (based on metrafenone total residue scenario ) Ecosystem Component Total concentration (μg/kg - ww) Lipid

norm alized concentration (μg/kg - lipid) Contribution

due to diet (μg/kg - ww) Contribution

due to respiration (μg/kg - ww) Small Fish 17,636 440909 862.94 16,773.41 Medium Fish 18,305 457626 1,651.07 16,653.98 Large Fish 19,586 489661 3,063.04 16,523.40Page 39 of 114 3. Measures of Terrestrial Ex posure
a. Terrestrial Exposure Modeling T - REX Exposure of free
- ranging terrestrial animals is a function of the timing and extent of pesticide application with respect to the location and behavior of those species. OPP’s terrestrial exposure model generates exposure estimates assuming that the animal is present on the use site at the time that pesticide levels are highest. The upper
- bound pesticide residue concentration on food items is calculated from both initial applications and an y additional application s, taking into account pesticide degradation between applications. Although this approach is conservative, it is reasonable, particularly when considering acute risks. For acute risks, the assumption is that the duration of exposure is a single day

and, a gain, occurs when residue levels are highest. In evaluating chronic risks, longer
- term exposure estimates are also based on the assumption that the animal is present on the use site when residue levels are highest and furthermore that it rep eatedl y forage s on the use site. The current screening
- level approach does not directly relate timing of exposure to critical or sensitive population, community , or ecosy stem processes. Given that the application timing and location is crop
- dependent, it is difficult t o address the temporal and spatial co
- occurrence of metrafenone use and sensitive ecological processes. However, pesticides are frequentl y used from spring through fall; crop cultivation frequentl y starts in the spring, hence uses of metrafenone are likel y to occur in spring and perhaps summer depending on the region . Spring and earl y summer are typically seasons of active migrating, feeding, and reproduction for many wildlife species. The increased energy demands associated with these activities (as oppos ed to hibernation, for example) can increase the potential for exposure to pesticide
- contaminated food items since agricultural areas can represent a concentrated source of relativel y easily obtained, high
energy food items. In this assessment, the spatial extent of exposure for terrestrial animal species is limited to the use area onl y and the area immediately surrounding the use area. Currently , the Agency

does not require toxicity

studies on reptiles and amphibians in support of pesticide registrations. To accommodate this data gap, birds are used as surrogates for terrestrial
- phase amphibians and reptiles. It is assumed that, given the usually lower metabolic demands of reptiles and amphibians compared to birds, exposure to birds would be greater due to higher relative food consumption. While this assumption is likely true, there are no supported relationships regarding the relative toxicity of a compound to birds and herpetofauna. The lack of toxicity data on reptiles and amphibians represents a source of uncertainty in this assessment. Tables 14 and 15 list selected predicted EECs for birds, reptiles, terrestrial amphibians, and mammals obtained from T
- REX simulations for the proposed use of metrafenone at the maximum label rates.Page 40 of 114

Table 14 . Terrest rial Food - Item Residue Estimates for Birds with Metrafenone Proposed Use on Grapes at 0. 3 lb s a.i./A (6 apps./year; 14 day app. interval) with a Foliar Dissipation Half - life default value of 35 Days . Crop Food Item Maximum Dose
- Based EECs (mg/kg) 1 Maximum

Dose
- Based EECs (mg/kg) 2 Maximum

Dose
- Based EECs (mg/kg) 3 Dietary
- Based EECs (ppm) 4 Grapes Short grass 274.49 156.52 70.08 241.01

Tall grass 125.81 71.74 32.12 110.46 Broadleaf plants/ small insects 154.40 88.04 39.42 135.57 Fruits, pods, seeds, lg . insects 17.16 9.78 4.38 15.06 1 Based on 20 gram birds (acute) 2 Based on 100 gram birds (acute) 3 Based on 1000 gram birds (acute) 4 Dietary
- based EECs apply to both acute and chronic exposure Table 15 . Terrestrial Food - Item Residue Estimates for Mamm als with Metrafenone Proposed Use on Grapes at 0.3 lbs a.i./A (6 apps./year; 14 day app. interval) with a Foliar Dissipation Half - life default value of 35 Days . Size Class (gram s) Adjusted

LD 50 1 EECs

Short Grass Tall Grass Broadleaf Plants/ Sm all Insec ts Fruits/Pods/ Seeds/ Large Insects Granivore Dose - Based Dose - Based Dose - Based Dose - Based Dose - Based 15 2225.56 229.78 105.32 129.25 14.36 3.19 35 1800.71 158.81 72.79 89.33 9.93 2.21 1000 778.86 36.82 16.88 20.71 2.30 0.51 Dietary - Based EECs 2 241. 01 110.46 135.57 15.06 Not applicable 1 Herbivores/ insectivores; Granivores 2 Dietary
- based EECs apply to both acute and chronic exposure TERRPLANT Effects on non
- target terrestrial plants are most likely to occur as a result of spray drift and/or runoff from ground applications. These are important factors in characterizing the risk of metrafenone to non
- target plants, which is assumed to reach off
- site soil. The TerrPlant (Ver.1.2.2) model predicts EECs for terrestrial plants located in dry and se mi
aquatic areas adjacent to the treated field. The EECs are based on the application rate and solubility

of the pesticide in water and drift characteristics. The amount of metrafenone that runs off is a proportion of the application rate and is assumed to be 1%, based on metrafenone’s solubility of <10 ppm (i.e. 0.474 mg/L) in water. Drift from ground applications are assumed to be 1% the application rate . An incorporation depth was not referenced in the label setting the default value to 1 inch for gro und applications. For a standard scenario on an agricultural field, the runoff scenario for terrestrial plants inhabiting dry

areas adjacent to a field is characterized as “sheet runoff” (one treated acre to an adjacent acre; a 1:1 ratio) and inhabiting s emi
- aquatic or wetland areas adjacent to a field is characterized as “channelized runoff” (10 treated acre to an adjacent low
- lying acre; a 10:1 ratio). The TerrPlant model EECs are presented in Table 16
.Page 41 of 114

Table 16 . Estimated Environmental Concentration s of Metrafenone for Terrestrial Plants from Grape Use Application Me thod Application

Rate (lbs a.i./A) Total Load ing to

Dry areas (lb/A) 1 Total Loading to Semi - Aquatic Areas (lb/A) 2 Drift (lb/A) 3 Ground 0.3 * 0.006 0.033 0.003 Ground 1.8 ** 0.036 0.198 0.018 1 EEC = Sheet Runoff + Drift (1% for ground) 2 EEC = Channelized Runoff + Drift = 1% for ground 3 EEC for gr ound (appl rate x 1% drift) * Maximum single application rate ** Maximum seasonal application rate

C. Ecological Effects Characterization

1. Aquatic Effects Characterization a. Aquatic Animals (1 ) Acute Effects Freshwater Fish and Aquatic

-Phase Amphibians
- Technical The freshwater fish studies on rainbow trout ( Oncorhynchus mykiss , MRID 47267443) and bluegill sunfish (

Lepomis macrochirus , MRID 47267442) are classified as supplemental for several reasons. The water samples were not centrifuged prior to anal yt ical determination. Without centrifugation, the amount of chemical that is freel y dissolved and bioavailable cannot be determined. Stability of exposure to the dissolved form throughout the test is unknown. This is especially a problem as some of the testi ng concentrations were conducted above the water solubility limit of the technical grade active ingredient ( 0.2
- 0.5 mg a.i./L at 12 o C ). Therefore, the concentrations are reported as mg ‘total’ a.i./Land are not useful for RQ calculations, but can contribute to risk description
. Freshwater Fish and Aquatic

-Phase Amphibians

– Metabolites / Degradates Similar to freshwater fish studies on the technical, the freshwater fish studies on degradate s of metrafenone on rainbow trout ( O. mykiss MRID 47267444 , 472674 45) are also classified supplemental. The water solubility limit was not given, and there was no report of whether the test solutions were centrifuged prior to anal yt ical determination of the test concentrations to ensure that the measured concentrations represent bioavailable material. For example, in the latter study (MRID 47267445), undissolved test substance (likely the result of exceeding the limit of water solubility of the test material) was noted at the bottom of the test vessel in all treatment ves sels throughout the definitive test. Again, the concentrations are reported as mg ‘total’ a.i./Land are not useful for RQ calculations, but can contribute to risk description
. Freshwater Fish and Aquatic

-Phase Amphibians
- Formulations Similar to the fre shwater fish technical grade and metabolite/degradate studies, the freshwater fish study on rainbow trout ( O. mykiss MRID 47267605) is also classified asPage 42 of 114

supplemental. There was no report of whether the test solutions were centrifuged prior to anal yt ical d etermination. Without centrifugation, the amount of chemical that is freel y dissolved and bioavailable cannot be determined. Stability of exposure to the dissolved form throughout the test is unknown; neither is the water solubility for this formulation ac tive ingredient. Again, the concentrations are reported as mg ‘total’ a.i./L and are not useful for RQ calculations, but can contribute to risk description
.

Table 17 . Freshwater Fish Acute Toxicity Data Comm on Name %AI Study param eters LC 50/NOAEC/LOAEC MRID Classification/ Category Technical AC 375839 (a.k.a. BAS 560F) Rainbow trout Oncorhynchus mykiss 97.1 96 hour flow
through study 2 reps / 10 fish per rep. Mean
- measured: <0.000498 (negative, solvent), 0.065, 0.13, 0.25, 0.43, and 0.82 mg total a.i. /L 96
- hr LC 50 > 0.82 mg total

a.i./L NOAEC: 0.25 mg total a.i./L Endpoint(s) affected: mortality, sublethal effects. Mortality Cumulative mortality after 96 hours was 0% among all fish in the negative and solvent control groups, and in the treatment group s exposed to 0.13 and 0.25 mg a.i./L of AC 375839. Cumulative mortality was 5% among fish exposed to 0.065, 0.43 and 0.82 mg a.i./L of AC 375839 after 96 hours. Sublethal effects No sublethal effects were observed among fish in the negative or solvent controls, 0.065, 0.13, 0.25 or 0.43 mg a.i./L treatment groups exposed to AC 375839 after 96 hours. Within the 0.82 mg a.i./L treatment group, 16% of fish still living were lethargic and 5% exhibited dark discoloration after 96 hours. 47267443 Supplemental (n ot to be used in risk estimation) / At most, Highly toxic 1Page 43 of 114 Table 17 . Freshwater Fish Acute Toxicity Data Comm on Name %AI Study param eters LC 50/NOAEC/LOAEC MRID Classification/ Category Bluegill sunfish Lepomis macrochirus 97.1 96 hour flow
through study 2 reps / 10 fish per rep. Mean
- measured: <0.000498 (negative, solvent), 0.066, 0.14, 0.25, 0.45, and 0.87 mg total a.i./L 96
- hr LC 50 > 0.87 mg total

a.i./L NOAEC: 0.45 mg to t al a.i./L Endpoint(s) affected: mortality, sublethal effects. Mortality Cumulative mortality after 96 hours was 0% among all fish in the negative and solvent control groups and all treatment groups except the 0.87 mg a.i./L treatment group in which 15% of fish died. Sublethal effects No sublethal effects were observed among fish in the negative or solvent controls, 0.066, 0.14, 0.25 or 0.45 mg a.i./L treatment groups exposed to AC 375839 after 96 hours. Within the 0.87 mg a.i./L treatment group, 18% of fish still living were lethargic and 12% were lying on the bottom of the test chamber with little mo tion other than gill mo vement after 96 hours. 47267442 Supplemental (not to be used in risk estimation) / At most , Highly toxic 1

Metabolites/ Degradates Rainbow trout Oncorhynchus mykiss 99.5 Reg. No. 4074484 (Metabolite of BAS 560 F) 96 hour static study; limit test 2 reps (neg. control), 3 reps (treatment) / 10 fish per rep. Mean
- measured: <1 (negative) and 99 mg total a.i./L 96
- hr LC 50 > 99 mg total a.i./L

NOAEC ≥ 99 mg total a.i./L Endpoint(s) affected: none. 47267444 Supplemental (not to be used in risk estimation) / At most, Slightly toxic 1Page 44 of 114 Table 17 . Freshwater Fish Acute Toxicity Data Comm on Name %AI Study param eters LC 50/NOAEC/LOAEC MRID Classification/ Category Rainbow trout Oncorhynchus mykiss 98.2 Reg. No. 4084564 (Metabolite of BAS 560F) 96 hour static study 1 rep / 10 fis h per rep. Mean
- measured: <1 (negative), 4.4, 9.2, 20.3, 35.2 and 58.4 mg total a.i./L 96
- hr LC 50 15.8 (9.2
- 35.2) mg

total a.i./L NOAEC: 9.2 mg total a.i./L Endpoint(s) affected: mortality, sublethal effects Mortality Cumulative mortality at 96 hours wa s 80% in the 20.3 mg total a.i./L concentration and 100% in the two highest concentrations. Sublethal effects Tottering and distended abdomen we re observed after 4 hours in the group exposed to 58.4 mg total a.i./L; also observed among those in the group exp osed to 20.3 mg total a.i./L between 24 and 72 hours. Apathy and distended abdomen were observed after 24 hours among those in the 35.2 mg total a.i./L treatment group and after 96 hours among those in the group exposed to 20.3 mg total a.i./L. 47267445 Su pplemental (not to be used in risk estimation)/ Slightly toxic 1

Form ulations Rainbow trout Oncorhynchus mykiss 24.7%

a.i.; 294 g BAS 560 00F/L BAS 560 00F (SF

10358, RLF 12359) 96 hour static study 2 reps. / 10 fish per rep. Mean
- measured: <4.05 (neg
. control), 12, 20, 34, 56, and 94 mg form/L [<1 (neg. control), 3.0, 4.9, 8.3, 13.7, and 23.3 mg total a.i./L] 96
- hr LC 50 >94 mg form/L

[>23.3 mg total a.i./L] NOAEC ≥ 94 mg form/L [23.3 mg total a.i./L] Endpoint(s) affected: none. 47267605 Supplemental (not to be used in risk estimation) / At most, Slightly toxic 1

1 Based on LC 50 (mg/L): < 0.1 very highly toxic; 0.1
- 1 highly toxic; >1
- 10 moderately toxic; >10
- 100 slightly toxic; >100 practically nontoxicPage 45 of 114

Freshwater Invertebrates
- Technical The freshwat er invertebrate study using the technical grade active ingredient on water flea ( Daphnia magna , MRID 47267437) is classified as supplemental. The water samples were not centrifuged prior to anal yt ical determination. Without centrifugation, the amount of ch emical that is freel y dissolved and bioavailable cannot be determined. Stability of exposure to the dissolved form throughout the test is unknown. This is especiall y a problem as some of the testing concentrations were conducted at or above the water solub ility

limit of the technical grade active ingredient (0.2
- 0.5 mg a.i./Lat 12 o C). Therefore, the concentrations are reported as mg ‘total’ a.i./Land are not useful for RQ calculations, but can contribute to risk description
. Freshwater Invertebrates

–Met abolites / Degradates Similar to freshwater invertebrate study on the technical, the freshwater invertebrate studies on degradates of metrafenone on the water flea ( D. magna MRID 47267438, 47267439) is also classified supplemental. The water solubility lim it was not given, and there was no report of whether the test solutions were centrifuged prior to anal yt ical determination of the test concentrations to ensure that the measured concentrations represent bioavailable material. Again, the concentrations are reported as mg ‘total’ a.i./Land are not useful for RQ calculations, but can contribute to risk description
. Freshwater Invertebrates

–Formulations Similar to the freshwater invertebrate technical grade and metabolite/degrad ate studies, the freshwater i nvertebrate study on water flea (

D. magna MRID 47267604 ) is also classified as supplemental. There was no report of whether the test solutions were centrifuged prior to anal ytical determination. Without centrifugation, the amount of chemical that is freel y dissolved and bioavailable cannot be determined. Stability of exposure to the dissolved form throughout the test is unknown; neither is the water solubility for this formulation active ingredient. Again, the concentrations are reported as mg ‘total’ a.i./ L and are not useful for RQ calculations, but can contribute to risk description
.Page 46 of 114 Table 18 . Freshwater Invertebrate Acute Toxicity Data Comm on Nam e %AI Study param eters EC 50/NOAEC/LOAEC MRID Classification / Category Technical AC 375839 ( a.k.a. BAS 560F) Water flea Daphnia magna 97.1 48 hour static study 2 reps.; 10 inverts. per rep Mean
- measured: <0.000498 (negative, solvent), 0.059, 0.12, 0.22, 0.45, and 0.92 mg total a.i./L 48
- hr EC 50 > 0.92 mg total a.i./L Slope: N/A NOAEC ≥ 0.92 mg total a.i./L Endpoint(s) affected: none. 47267437 Supplemental (not to be used in risk estimation) / At most, Highly toxic 1

Metabolites/ Degradates Water flea Daphnia magna 99.5 CL 375816 48 hour static study 4 reps.; 5 inverts per rep. Mean
- measured: <1 (negative), 12.9, 25.8, 51.4, and 102.5 mg total a.i./L 48
- hr EC 50 > 102.5 mg total a.i. /L Slope: N/A NOAEC ≥ 102.5 mg total a.i./L Endpoint(s) affected: none. 47267438 Supplemental (not to be used in risk estimation) / Practically non - toxic 1
Water flea Daphnia magna 98.2 CL 4084564 48 hour static study 4 reps.; 5 inverts per rep. Mean
- measured: <1 (negative) , 6.4, 12.5, 23.2, 49.6, 66.4 mg a.i./L 48
- hr EC 50 = 50.9 (42.1
- 63.5) mg total a.i./L Slope: 4.59 (2.52
- 6.66) NOAEC = 23.2 mg total a.i./L Endpoint(s) affected: immobility. Immobility Cumulative immobility was 0% among all daphnids exposed to 0 (negativ e control), 6.4 and 12.5 mg total a.i./L of CL 4084564 (Metabolite of BAS 560 F) after 48 hours. Cumulative immobility wa s 5% among animals exposed to 23.2 mg total a.i./L, 55% among daphnids exposed to 49.6 mg total a.i./L and 65% among animals exposed to 66.4 mg total a.i./L of CL 4084564 (Metabolite of BAS 560 F) after 48 hours. 47267439 Supplemental (not to be used in risk estimation) / Slightly toxic 1Page 47 of 114 Table 18 . Freshwater Invertebrate Acute Toxicity Data Comm on Nam e %AI Study param eters EC 50/NOAEC/LOAEC MRID Classification / Category Form ulation s Water flea Daphnia magna 24.7%

a.i.; 294 g BAS 560 00 F/L BAS 560 00 F (SF 10358,

RL F 12359) 48 hour static study 2 reps.; 10 inverts per rep. Mean
- measured: <0.810 (neg. control), 1.7, 3.1, 6.1, 12.2, 24.3, and 47.1 mg form/L [<0.20 (neg. control), 0.42, 0.76, 1.5, 3.0, 6.0, and 11.6 mg total a.i./L] 48
- hr EC 50 : 17.1 (12.8
- 24.3) mg fo rm /L [4.2 (3.2
- 6.0) mg total a.i./L] NOAEC: 6.1 mg form/L [1.5 mg total a.i./L] Endpoint(s) affected: mortality and sublethal effects (immobility) Mortality Cumulative mortality after 48 hours was 0% among animals exposed to mean
- measured concentrations of 0 (negative control), 1.7, 3.1, 6.1 and 12.2 mg form/L . Cumulative mortality was 65% among animals exposed to 24.3 mg form/L and 90% among animals exposed to 47.1 mg form/L after 48 hours. Immobility Cumulative i mmobility aft 48 hours was 0% at mean
- me asured concentrations of 1.7 and 47.1 mg form/L; 5% at neg. control, 3.1, and 6.1 mg form/L; 15% at 12.2 mg form/L; and, 25% at 24.3 mg form/L. 47267604 Supplemental (not to be used in risk estimation) / Moderately toxic 1

1 Based on EC 50 (mg/L): < 0.1 v ery highly toxic; 0.1
- 1 highly toxic; >1
- 10 moderately toxic; >10
- 100 slightly toxic; >100 practically nontoxic
Marine/Estuarine Fish Unlike the majority

of the aquatic studies, which were supplemental on account of not having centrifuged samples which clearl y exceeded the water solubility limit, the marine/estuarine fish study on the sheepshead minnow ( Cyprinodon variegatus , MRID 47267446) is acceptable on account of having centrifuged the two highest concentrations, both of which were above the solubi lity limit of 0.3 mg a.i./L (in saltwater). The results reveal no effects on mortality or sublethal effects.Page 48 of 114 Table 19 . Marine/ Estuarine Fish Acute Toxicity Data Comm on Name %AI Study param eters LC 50/NOAEC/LOAEC MRID Classification/ Category Technica l AC 375839 (a.k.a. BAS 560F) Sheepshead Minnow Cyprinodon variegatus 94.2 96 hour flow
- through study 2 reps / 10 fish per rep. Mean
- measured: <0.04 (negative, solvent), 0.072, 0.13, 0.24, 0.32 (0.13 mg a.i./L based on centrifuged samples) and 0.65 (0.35 mg a.i./L based on centrifuged samples) mg a.i./L 96
- hr LC 50 > 0.35 mg dissolved

a.i./L NOAEC ≥ 0.35 mg dissolved a.i./L Endpoint(s) affected: none. 47267446 Acceptable/ At most, Highly toxic 1

1 Based on LC 50 (mg/L): < 0.1 very highly toxic; 0.1
- 1 highly toxic; >1
- 10 moderately toxic; >10
- 100 slightly toxic; >100 practically nontoxic

Marine/Estuarine Invertebrates

– Technical The marine/estuarine invertebrate study using the technical grade active ingredient on eastern o ys ter ( Crassostrea virginica , MRID 47267440) is classified as supplemental. Given that centrifugation was not performed o n all concentration test levels, it is possible that the endpoint retrieved from this study will provide an underestimation of risk. For example, we know that after centrifugation of the highest test level the mean
- measured concentration decreased by 42% r elative to the pre
- centrifugation mean
- measured concentration. The reduction in soluble substance is likely due to the concentration being above the limit of solubility ( i.e. , 0.3 mg a.i./L). Nevertheless, it is unknown from the study results whether a sim ilar reduction will occur at lower concentrations, including one more above the limit of solubility and the three levels remaining below the limit of solubility
. Similarly , the saltwater m ys id study ( Americamysis bahia , MRID 47267441) is classified supplem ental on account of no centrifugation of water samples at any test concentration level prior to analy tical determination. Without centrifugation, the amount of chemical that is freel y dissolved and bioavailable cannot be determined. Stability of exposure to the dissolved form throughout the test is unknown. Therefore, the concentrations are reported as mg ‘total’ a.i./L and are not useful for RQ calculations, but can contribute to risk description
.Page 49 of 114 Table 20 . Marine/ Estuarine Invertebrate Acute Toxic ity Data Comm on Nam e %AI Study param eters EC 50/LC 50/NOAEC/LOAEC MRID Classification/ Category Technical AC 375839 (a.k.a. BAS 560F) Eastern oyster Crassostrea virginica 94.2 96 hour flow
- through study 20 bivalves per level Time - weighted average: <0.04 ( negative, solvent), 0.0522, 0.104, 0.203, 0.287, and 0.573 mg total a.i./L (highest concentration centrifuged yielded 0.33 mg dissolved a.i./L) 96
- hr EC 50 : 0.22 (0.20
- 0.25) mg

total a.i./L 2 NOAEC: 0.0522 mg total a.i./L Endpoint(s) affected: shell deposition. Shell deposition Relative to the negative control, the mean percent reduction in shell growth starting with the negative solvent is as follows: 17.4, 13.9, 26.3, 44.3, 84.2, and 100%, respectively. No significant differences (

p = 0.05) were detected between the two controls. 47267440 Supplemental (not to be used in risk estimation) / Highly toxic 1

Saltwater mysid Americamysis bahia 94.2 96 hour flow
- through study 2 reps./ 10 mysids per rep. Time - weighted average: <0.04 (negative, solvent), 0.0749, 0 .129, 0.240, 0.416, and 0.663 mg total a.i./L 96
- hr LC 50 : 0.487 (0.428
- 0.575)

mg total a.i./L 2 NOAEC: 0.0749 mg total a.i./L Endpoint(s) affected: mortality, sublethal effects. Mortality At 96 hours, cumulative mortality at the TWA concentrations 0.129 and 0.240 mg total a.i./L was 5%, at 0.416 mg total a.i./L was 15%, and at 0.663 mg total a.i./L was 95%. Sublethal effects No sub
- lethal effects were observed in the controls or TWA 0.0749
- 0.240 mg total ai/L treatment levels. At test termination 7 out o f the surviving 17 mysids in the 0.416 mg total ai/L level and the single surviving mysid at the 0.663 mg total ai/L level were observed swimming erratically. 47267441 Supplemental (not to be used in risk estimation) / Highly toxic 1

1 Based on EC 50 (mg/L): < 0.1 very highly toxic; 0.1
- 1 highly toxic; >1
- 10 moderately toxic; >10
- 100 slightly toxic; >100 practically nontoxic 2 Range is 95% confidence interval for endpointPage 50 of 114

(2 ) Chronic Effects Freshwater Fish

– Technical The freshwater fish study on fathead minnow ( Pimephales promelas , MRID 47267449) is classified as supplemental
. The solubility limit of the test compound is not reported; it is possible given previous reports that the limit was approximately 0.2
- 0.5 mg a.i./L at 12 o C, which implies that the two highest test concentrations (0.421 and 0.839 mg total a.i./L) potentially

exceeded the solubility

limit and yet centrifugation (or filtration) was not mentioned as part of the protocol prior to analytical determination. Without centrifugation, the amo unt of chemical that is freely dissolved and bioavailable cannot be determined. Stability

of exposure to the dissolved form throughout the test is unknown. Therefore, the concentrations are reported as mg ‘total’ a.i./Land are not useful for RQ calculatio ns, but can contribute to risk description
. Hatching occurred at all levels on Day 4 , and hatching success averaged 88
- 94% for all levels, with no statistically significant differences observed. Post
- hatch survival (28
- day s post - hatch) was statistically
- reduced compared to the negative control at the 227, 421, and 839 μg total a.i./Ll evels (p ≤0.05). P ost - hatch survival averaged 96% at the negative control through 118 μg total a.i./Ll evels, and 87, 86, and 11% at the 227, 421, and 839 μg total ai/Ll eve ls, respectivel y. N o clinical signs of toxicity w ere observed during the study i n an y treatment group. F ish length was significantly r educed relative to the average negative control length at levels above 421 μg total ai/L and wet and dry w eight were significantl y lower than the negative control weights at the 839 μg total ai/Ll evel; however, significant impact on survival occurred at these levels.

Table 21 . Freshwater Fish Chronic Toxicity Data Comm on Name %AI Study param eters NOAEC/LOAEC MRID Cla ssification /Category Technical AC 375839 (a.k.a. BAS 560F) Fathead minnow Pimephales promelas 97.1 32
- day flow
- through test 80 embryos per level, split into 20 embryos per cup, 1 cup per aquarium, 4 rep. aquaria per treatment Time - weighted average: <0.49 8 (negative, solvent), 57, 118, 227, 421, and 839 μg total a.i./L NOAEC: 0.118 m g total a.i./L LOAEC: 0. 227 mg total a.i./L Most sensitive endpoint: post
hatch survival Endpoint(s) affected: post
- hatch survival and growth (total length, wet and dry weight) 47267449 Supplemental (not to be used in risk estimation)Page 51 of 114

Freshwater Invertebrates

– Technical A chronic freshwater invertebrate study (MRID 47267447) with metrafenone technical (97.1%) was deemed invalid due to instability of the chemical under t est conditions
. A non - guideline chronic midge study ( Chironomus riparius , MRI D 47267501) with metrafenone technical (97.1%) is also invalid on the basis of low negative control emergence. Marine/Estuarine Fish No chronic marine/estuarine fish studies were submitted for review.
Marine/Estuarine Invertebrates
- Technical The marine/estuarine invertebrate study on saltwater my sid (

Americamysis bahia , MRID 47267448) is classified as acceptable. Although the solubility limit of the test compound is not report ed; it is possible given previous reports that the limit was approximately 0.2
- 0.5 mg a.i./L at 12 o C. The mean
- measured test concentrations of the total metrafenone present do not exceed the suggested solubility limit. Inaddition, the highest nominal con centration (0.05 mg a.i./L) is significantl y below solubility ( i.e. , ≥ 4
- 10 times); in this particular case, not centrifuging is considered to not affect acceptability of the study
. Finally , given the dilution sy stem design, where the stock solution was a solvent stock solution suggests that solubility of the compound is not an issue in this particular case. The day of first brood release was not assessed. The number of offspring per surviving female was statistically
- reduced compared to the negative co ntrol at the 45 μg ai/L level (1.4 versus 5.8 offspring/female). Similarl y, the number of offspring per female per reproductive day

was statistically
- reduced compared to the negative control at the 45 μg ai/L(0.10 versus 0.44 offspring/female/day). Although not stat istically
- compared, the percentage of females producing young averaged ≥85% at the control through 22 μgai/L treatment levels, but only 25% at the 45 μg ai/Llevel. The NOAEC for reproductio n was reported to be 22 μg ai/L.Page 52 of 114 Table 22 . Mar ine/ Estuarine Invertebrate Chronic Toxicity Data Comm on Name %AI Study param eters NOAEC/LOAEC MRID Classification /Category Technical AC 375839 (a.k.a. BAS 560F) Saltwater mysid Americamysis bahia 94.2 28
- day flow
- through test Before pairing: 60 mysids per level After pairing: 20 mysids per level Time - weighted average: <LOD (negative, solvent), 2.8, 6.2, 12, 22, and 44 μg total a.i./L NOAEC: 0.022 m g a.i./L 1 LOAEC: 0.0 44 mg a.i./L Most sensitive endpoint: reproduction (number of offspring/female/repro . day) Endpoint(s) affected: reproduction (number of offspring/female/repro. day) 47267448 Acceptable

1 Bold value is the value that will be used to calculate risk quotients

b. Aquatic Plants Vascular Aquatic Plants The vascular aquatic plant study (MRID 47267511) on duckweed ( Lemna gibba ) is classified as supplemental for several reasons , which are considered major guideline deviations . The test was conducted for 7 day s instead of the guideline prescribed 14 day s . More importantly , the dissolved or solub le concentrations ( i.e. , post - centrifugation) of test material were not determined. As a result of the latter, the stability of exposure to the dissolved form throughout the test is unknown. This is especially a problem as some of the testing concentration s were conducted above the solubility limit of the technical grade active ingredient (0.457 mg/L in water; 0.3 mg/L in 20X AAP media both at pH9). Therefore , the concentrations are reported as mg ‘total’ a.i./Land are not useful for RQ calculations, but c an contribute to risk description
. Non

- vascular Aquatic Plants
- Technical The non
- vascular aquatic plant stu dies on cyanobacteria ( Anabaena flos

- aquae ; MRID 47267512), marine diatom (Skeletonema costatum , MRID 47267513 ), freshwater diatom ( Navicula pelliculosa , MRID 47267514 ) , and green algae ( Pseudokirchneriella subcapitata , MRID 47267515) are classified as supplemental for several reasons. The water samples were not centrifuged prior to anal yt ical determination. Without centrifugation, the amount of ch emical that is freely dissolved and bioavailable cannot be determined. S tability

of exposure to the dissolved form throughout the test is unknown. This is especially

a problem as some of the testing concentrations were conducted above the solubility

limit of the technical grade active ingredient (0.457 mg/L in freshwater ; 0.3 mg/L in saltwater). Therefore, the concentrations are reported as mg ‘total’ a.i./L and are not useful for RQ calculations, but can contribute to risk description
.Page 53 of 114

Non

- vascular Aqua tic Plants

– Metabolites / Degradates Similar to the non
- vascular aquatic plant technical grade studies, the non
- vascular aquatic plant studies on the degradates are classified as supplemental for several important reasons. For example, the algae study ( Ps eudokirchneriella subcapitata MRID 47267516) did not report daily observations of test solution appearance, metabolite water solubility , and method of filtration of test solution, which leads to uncertainty in the measured concentrations as well as the rel ationship of mean
- measured and nominal concentrations relative to the metabolite water solubility value. For this reason too, the concentrations are reported as mg ‘total’ a.i./L and are not useful for RQ calculatio ns, but can contribute to risk descriptio n . Inaddition, the other algae study (Pseudokirchneriella subcapitata MRID 47267517) did not centrifuge the water samples prior to anal yt ical determination. Without centrifugation, the amount of chemical that is freel y dissolved and bioavailable cannot be determined. Stability of exposure to the dissolved form throughout the test is unknown ; neither is the metabolite water solubility . Again, the concentrations are reported as mg ‘total’ a.i./L and are not useful for RQ calculations, but can contribute to risk description
. Non

- vascular Aquatic Plants
- Formulations Similar to the non
- vascular aquatic technical grade and metabolite/degradate studies, the non - vascular aquatic plant study on the green algae (

Pseudokirchneriella subcapitata ) is also classified as supplemental. Although centrifugation was conducted on the water samples in this particular case the protocol states that it was used to remove algal cells, which suggests that the centrifugation method may not have removed the undissolved material. Without centrifugation, the amount of chemical that is freely dissolved and bioavailable cannot be determined. Stability of exposure to the dissolved form throughout the test is unknown; neither is the water solubility for this formulation active ingredient. Again, the concentrations are reported as mg ‘total’ a.i./Land are not useful for RQ calculatio ns, but can contribute to risk description
.Page 54 of 114 Table 23 . Aquatic Plant Toxicity Data Species %A.I. Study Param eters EC 50/NOAEC MRID No. Study

Classification Technical AC 375839 (a.k.a. BAS 560F) Vascular Aquatic Plants Duckweed Lemna gibba 94.2 Tier II study 7 day static rene wal study 3 reps. / 4 plants per rep. Mean measured: <0.04 (negative, solvent), 0.057, 0.10, 0.21, 0.41, and 0.76 mg a.i./L Biomass (dry weight) EC 50 > 0.76 mg total a.i./L NOAEC: 0.21 mg total a.i./L Frond density EC 50 > 0.76 mg total a.i./L NOAEC: 0.41 mg total a.i./L Grow th rate EC 50 > 0.76 mg total a.i./L NOAEC: 0.41 mg total a.i./L Most sensitive endpoint: biomass based on NOAEC Endpoint(s) affected: biomass, frond density, grow th rate 47267511 Supplemental (do not use in risk estimation)

Non
- Vascular Aquatic Plants Cyanobacteria (blue
green algae) Anabaena flos

- aquae 94.2 Tier II study 96 hour static study 3 reps. Initial measured: <0.04 (negative, solvent), 0.0883, 0.139, 0.217, 0.580, and 0.862 mg a.i./L Biomass (area under grow th curve), cell density, grow th rate EC 50 > 0.862 mg total a.i./L NOAEC ≥ 0.862 mg total a.i./L Endpoint(s) affected: none. 47267512 Supplemental (do not use in risk estimation)Page 55 of 114 Table 23 . Aquatic Plant Toxicity Data Species %A.I. Study Param eters EC 50/NOAEC MRID No. Study

Classification Marine Diatom Skeletonema costatum 94.2 Tier II study 96 hour static study 3 reps. Initial measured: <0.04 (negative, solvent), 0.0509, 0.109, 0.21 4, 0.272, and 0.680 mg a.i./L Biomass (area under grow th curve) EC 50 : 0.57 (0.38
- 0.85) mg total a.i./L NOAEC: 0.0509 mg total a.i./L Cell density EC 50 > 0.680 mg total a.i./L NOAEC: 0.272 mg total a.i./L Grow th rate EC 50 > 0.680 mg total a.i./L NOAEC: 0. 272 mg total a.i./L Most sensitive endpoint: biomass Endpoint(s) affected: biomass, cell density, grow th rate 47267513 Supplemental (do not use in risk estimation)

Freshwater Diatom Navicula pelliculosa 94.2 Tier II study 96 hour static study 4 reps. I nitial measured: <0.04 (negative, solvent), 0.0761, 0.154, 0.276, 0.432, and 0.914 mg a.i./L Biomass (area under grow th curve) EC 50 > 0.914 mg total a.i./L NOAEC: 0.432 mg total a.i./L Cell density EC 50 > 0.914 mg total a.i./L NOAEC: ≥ 0.914 mg total a.i./L Grow th rate EC 50 > 0.914 mg total a.i./L NOAEC: ≥ 0.914 mg total a.i./L Endpoint(s) affected: biomass based on NOAEC 47267514 Supplemental (do not use in risk estimation)Page 56 of 114 Table 23 . Aquatic Plant Toxicity Data Species %A.I. Study Param eters EC 50/NOAEC MRID No. Study

Classification Green Algae Pseudokirchneriella subcapitata 97.1 Tier I study 72 hour static stu dy 6 reps. (negative, solvent controls); 3 reps. (treatments) Mean
- measured: <0.498 (negative, solvent), 60, 123, 232, 472, and 870  g a.i./L Biomass (area under grow th curve) EC 50 : 0.71 ( 0.65
- 0.77 ) m g total a.i./L NOAEC: 0.23 mg total a.i./L Cell density EC 50 : 0.74 ( 0.67
- 0.82 ) m g total a.i./L NOAEC: 0.23 mg total a.i./L Grow th rate EC 50 > 0.87 m g total a.i./L NOAEC: 0.23 mg total a.i./L Most sensitive endpoint: biomass Endpoint(s) affected: biomass, cell density, grow th rate 47267515 Supplemental (do no t use in risk estimation)

Metabolites/ Degradates Non
- Vascular Aquatic Plants Algae Pseudokirchneriella subcapitata 99.5 CL 375816 (Metabolite of BAS 560 F) Tier I study 72 hour static study 5 reps. (negative control); 3 reps. (treatments) Mean
- measured: ND (negative), 6.50, 12.66, 25.80, 51.45, and 101.92 mg a.i./L Biomass (area under grow th curve), Chlorophyll
- a, and Grow th rate EC 50 > 101.9 mg total a.i./L NOAEC ≥ 101.9 mg total a.i./L Endpoint(s) affected: none. 47267516 Supplemental (do not use in risk estimation)Page 57 of 114 Table 23 . Aquatic Plant Toxicity Data Species %A.I. Study Param eters EC 50/NOAEC MRID No. Study

Classification Algae Pseudokirchneriella subcapitata 98.2 CL 4084564 (Metabolite of BAS 560 F) Tier I study 72 hour static study 5 reps. (negative control); 3 reps. (treatments) Mean
- measured: ND (negative), 3.21, 6.28, 9.9, 18.57, 38.78, and 58.03 mg a.i./L Chlorophyll
- a EC 50 : 24 (21
- 27) mg total a.i./L NOAEC: 9.9 mg total a.i./L Biomass (area under grow th curve) EC 50 : 26 (22
- 30) mg total a.i./L NOAEC: 9.9 mg total a.i./L Grow th rate EC 50 : 44 (40
- 47) mg total a.i./L NOAEC: 9.9 mg total a.i./L Mo st sensitive endpoint: chlorophyll
- a Endpoint(s) affected: chlorophyll
- a, biomass, and grow th rate 47267517 Supplemental (do not use in risk estimation)

Form ulations Non
- Vascular Aquatic Plants Green Algae Pseudokirchneriella subcapitata 24.7 BAS 560 00 F (SF 10358, RLF 12359) Tier I study 72 hour static study 6 reps. (negative control); 3 reps. (treatments) Initial mean
- measured: <0.05 (negative), 0.188, 0.371, 0.716, 1.383, 2.717, and 5.681 mg a.i./L Cell density EC 50 : 0.66 (0.47
- 0.91) mg total a.i./L NOAEC: 0.188 mg total a.i./L Biomass (area under grow th curve) EC 50 : 0.73 (0.53
- 0.99) mg total a.i./L NOAEC: 0.188 mg total a.i./L Grow th rate EC 50 : 5.2 (4.4
- 6.2) mg total a.i./L NOAEC: 0.188 mg total a.i./L Most sensitive endpoint: cell density Endpoi nt(s) affected: cell density, biomass, growth rate 47267607 Supplemental (do not use in risk estimation)Page 58 of 114

2. Terrestrial Effects Characterization a. Terrestrial Animals (1 ) Acute Effects Birds

– Technical The acute avian oral studies (MRID 47267502, 4 7267503) on 23
- week old Northern bobwhite quail ( Colinus virginianus ) and 20
- week old mallard duck ( Anas platyrhynchos ), respectively , assessed over 14 day s are classified as acceptable. A C 375839 Technical was administered to the birds via gelatin capsul es at nominal levels of 0 (vehicle control), 400, 600, 900, 1350, and 2025 mg ai/kg bw (limit dose). T he 14
- day acute oral LD 50 was >2025 mg ai/kg bw (>limit dose). T he 14
- day N OAELw as 2025 mg ai/kg bw, as there were no mortalities, clinical signs of to xicity , or treatment - related effects on body

w eight or food consumption during the 14
- day s tudy
. In addition, no toxicological effects were observed at necrops y. A C 375839 Technical (metrafenone) would be classified as practicall y non - toxic to yo ung adul t Northern bobwhite quail ( C. virginianus ) as well as to young adult mallard duck ( A. platyrhynchos ) in accordance with the classification s ystem of the U.S. EPA. The acute avian dietary studies (MRID 47267504, 47267505) on 11
- day o ld Northern bobwhite quail ( C. virginianus ) and 9
- day o ld mallard duck (

A. platyrhynchos ), respectivel y, assessed over 8 day s are classified as acceptable. AC 375839 Technical was administered to the birds in the diet at nominal concentrations of 0 (negative control), 100, 270 , 729, 1968, and 5314 mgai/kg diet (adjusted for purity). M ean - measured concentrations were <3.6 (<LOD, control), 98, 262, 809, 2130, and 6070 mg ai/kg diet, respectivel y. The 8
- day

a cute dietary

L C 50 was >6070 mg ai/kg diet. Given there was no dose
- re sponse, the NOAEC was the highest concentration tested, 6070 mg a.i./kg diet. There were no treatment - related mortalities, clinical signs of toxicity , or effects on food consumption. S ome gross pathological changes were observed. A C 375839 Technical (metrafenone) would be classified as practically n on - toxic to juvenile bobwhite quail ( C. virginianus ) as well as to juvenile mallard duck ( A. platyrhynchos ) on an acute dietary basis, in accordance with the classification s ys tem of the U.S. EPA.
Table 24 . Avian Acute Toxicity Data Comm on Name %AI Study param eters LD 50/LC 50 NOAEL/ LOAEL MRID Classification /Category Technical AC 375839 (a.k.a. BAS 560F) Northern Bobwhite Quail Colinus virginianus 95.86 Ac ute oral study 5 birds/sex/dose level 14 day observ ation period Nominal: 0 (vehicle), 400, 600, 900, 1350, and 2025 mg a.i./kg bw LD 50 > 2025 mg a.i./kg bw NOAEL: 2025 mg/kg bw Probit slope: N/A Endpoint(s) affected: none. 47267502 Acceptable/ Practically non - toxic 1Page 59 of 114 Table 24 . Avian Acute Toxicity Data Comm on Name %AI Study param eters LD 50/LC 50 NOAEL/ LOAEL MRID Classification /Category Mallard Duck Anas platyrhynchos 95. 86 Ac ute oral study 5 birds/sex/dose level 14 day observation period Nominal: 0 (vehicle), 400, 600, 900, 1350, and 2025 mg a.i./kg bw LD 50 > 2025 mg a.i/kg bw NOAEL: 2025 mg a.i./kg bw Probit slope: N/A Endpoint(s) affected: none. 47267503 Acceptable/ P ractically non - toxic 1

Northern Bobwhite Quail Colinus virginianus 95.86 Ac ute dietary study 12 birds per rep.(neg. control & treatment); 3 reps. (neg. control), 1 rep. per treatment 5 days on treatment, 3 additional days observation Mean
- measured: <3.6 ( neg. control), 98, 262, 809, 2130, and 6070 mg a.i./kg diet LC 50 >6070 mg a.i./kg diet NOAEC: 6070 mg a.i./kg diet LOAEC >6070 mg a.i./kg diet Issues 3 : body weight change (significant reduction in body weight gain (39%, relative to Control 1) at the 262 mg ai/kg diet level) . However, no concentration
- response was observed so it may not be biologically significant. 47267504 Acceptable/ Practically non - toxic 2

Mallard Duck Anas platyrhynchos 95.86 Ac ute dietary study 12 birds per rep.(neg. control & treatment); 3 reps. (neg. control), 1 rep. per treatment 5 days on treatment, 3 additional days observation Mean
- measured: <3.6 (neg. control), 98, 262, 809, 2130, and 6070 mg a.i./kg diet LC 50 > 6070 mg a.i./kg diet NOAEC: 6070 mg a.i./kg diet LOAEC >6070 mg a.i ./kg diet Issues 3 : body weight change (significant reduction in body weight gain (19%, relative to controls) at the 262 mg ai/kg diet level) . However, no concentration
- response was observed so it may not be biologically significant. 47267505 Acceptable/ P ractically non - toxic 2

1 Based on LD 50 (mg/kg) <10 very highly toxic; 10
- 50 highly toxic; 51
- 500 moderately toxic; 501
- 2000 slightly toxic; >2000 practically nontoxic 2 Based on LC 50 (mg/kg) <50 very highly toxic; 50
- 500 highly toxic; 501
- 1000 moderately toxic; 1001
- 5000 slightly toxic; >5000 practically nontoxic 3 The Northern bobwhite and mallard duck acute dietary studies were conducted at the same time in the same laboratory using the same feed. Therefore, the observance of body weight change at the same concentration level (262 mg a.i./kg diet) in both studies calls into question the validity of the effect as a result of the chemical versus some other factor.
Mammals
- Technical In an acute oral toxicity

study (MRID 47267522), three per sex, faste d, young adultPage 60 of 114

C57BL mice [(age: 8
- 13 weeks old, wt. males 23.0
- 25.7g, females 17.0
- 18.7g )] were given a single oral dose of the test material (BAS 560 F) prepared in 0.5% CMC solution in doubly distilled water in a sequential manner at a dose level of 2 000 mg/kg bw by gavage and observed for 14 day s. The three females were dosed in step 1, and the three males in step 2. The oral LD 50 is > 2000 mg/kg in mice which classifies the product (metrafenone technical) in EPA Toxicity Category III for oral toxicity. One male animal died on Day 4. This animal showed poor general health, dy spnea, tremor, piloerection and sunken flanks. The dead mouse showed discoloration of the lungs, and ulcer/erosion in stomach. All other male and female animals survived showed no obnormalities, and gained body weight during the first week post
- exposure. No gross abnormalities were noted for an y of the surviving animals when necropsied at the termination. Mammals

– Formulation In an acute oral toxicity

study (MRID 47267609), 5/s ex of Sprague
- Dawley derived (Crl:CD(SD)BR) albino rats (age: 8 weeks; weight: 206
- 229 g males and 165
- 184 g females) were given a single oral dose of AC 375839 300 g/L SC (RLF12359) (Lot No. R2066
- 048; 294 g/L and 25.21% AC 375839; density 1.19 g/mL ; pH 6.6; viscous beige liquid) as received at a dose of 5000 mg/kg bw administered by oral gavage. The amount of test solution to be administered was calculated for each animal. Animals were observed for clinical signs of toxicity and mortality

several times on the day

of dosing and daily f or 14 day s. Individual body weights were recorded prior to dosing (day 0) and on day s 7 and 14. A gross necrops y examination was performed on all animals at scheduled euthanasia. All animals survived and gained weight. No c linical signs of toxicity were observed. No gross pathological findings were observed at necrops y. The oral LD 50 is > 5000 mg/kg in rats which classifies the product (metrafenone formulation) in EPA Toxicity

Category IV for oral toxicity
.

Table 25 . Mam malian Acute Toxicity Data Comm on Nam e %AI Study param eters LD 50 /NOAEL MRID Classification /Category Technical AC 375839 (a.k.a. BAS 560F) Mouse 94.2 Ac ute oral study 2000 mg technical/kg bw (limit test) administered by gavage 3/sex/dose level 14
- day o bservation period Ac ute oral LD 50 > 2000 mg technical/kg bw

(F, M, both) 2 NOAEL: No NOAEL LOAEL: No LOAEL 47267522 Acceptable/ Practically non - toxic 1Page 61 of 114 Table 25 . Mam malian Acute Toxicity Data Comm on Nam e %AI Study param eters LD 50 /NOAEL MRID Classification /Category Form ulation Laboratory albino rat 25.21%;

AC 375839 300 g/ L SC (RLF 12359) Ac ute oral study

5000 mg fo rm

/kg bw (limit test) administered by gavage 5/sex/dose level 14
- day observation period Ac ute oral LD 50 >5000 mg form/kg bw (F,

M, both) [> 1,260.5 mg a.i./kg bw] 3 NOAEL: No NOAEL LOAEL: No LOAEL 47267609 Acceptable 4/ Practically non - toxic 1

1 Based on L D 50 (mg/kg) <10 very highly toxic; 10
- 50 highly toxic; 51
- 500 moderately toxic; 501
- 2000 slightly toxic; >2000 practically nontoxic 2 One male animal died on Day 4. This animal showed poor general health, dyspnea, tremor, piloerection and sunken flanks. Th e dead mouse showed discoloration of the lungs, and ulcer/erosion in stomach. 3 All animals survived and gained weight. No clinical signs of toxicity were observed. No gross pathological findings were observed at necropsy. 4 The study satisfies the OECD Guideline 401, which is no longer considered an acceptable protocol. The preferred protocol is OECD 425: Acute Oral Toxicity
- Up
- and
- Down Procedure.
Terrestrial Invertebrates

– Technical The terrestrial invertebrate study on honey bees ( Apis mellifera , MRID 47267508) classified as acceptable. The contact test had 4% mortality in the negative and solvent control s and 0% mortality in the 100 μg a.i./bee level by 48 hours ; there were no sub
lethal effects in the contact test. The oral test also had 4% morta lity in the negative control, 2% mortality

in the solvent control, and 2% mortality in the 114 μg a.i./bee level at 24 and 48 hours ; sub
- lethal effects were 0% in the negative control, 2% in the solvent control, and 6% in the 114 μg a.i./bee level onl y at 4 hours
. In a 14 day

acute limit toxicity

study , earthworms (

Eisenia fetida , MRID 47267518) were exposed to AC 375839 at a nominal concentration of 1000 mg a.i./kg dry weight of artificial soil. No concurrent reference chemical test was conducted in this study . The report indicated that the experiment was carried out in accordance with OECD 207. However, only

one concentration was tested which did not fulfill the requirement of the guideline. No earthworm mortality was observed in the water control or test substance treatment. There was one mortality in the acetone control group. The 14 day L C 50 was > 1000 mg a.i./kg dry

soil, the concentration tested. No significant difference in earthworm burrowing time ( i.e., time needed for 10 earthworms to burrow into the soil after placement on soil surface) was observed. The average weight loss between Day 0 and Day 14 was 20.6, 3.5 and 39.7 mg in the test groups of water control, acetone control, and test substance treatment, respectively . There was a significant dif ference in weight change between acetone control and test substance treatment. However, there was no significant difference between the water control and the test substance. Therefore, the sub
- lethal effect of AC 375839 at a concentration of 1000 mg a.i./kg dry wt soil onPage 62 of 114

weight loss is uncertain. The end
- point toxicity concentration of AC 375839 can not be determined from this study , however, it is considered to be non
- lethal to earthworms up to a concentratio n of 1000 mg a.i./kg dry soil. No other observable compound related toxicity effect was reported. Terrestrial Invertebrates

– Metabolites In a 14 day

acute toxicity study , earthworms ( E. fetida , MRID 47267519) were exposed to CL377160 at nominal concentrations of 0, 198, 296, 444, 667, and 1000 mg C L 377160/kg dry

weight of artificial soil. No concurrent reference chemical test was conducted in this study , however, the facility conducts annual test with 2
- chloroacetamide in a concentration range of 0

– 30 mg/kg dw of soil. The experiment was carried out in accordance with OECD 207. There were no observable compound related toxicity effects. No sub
- lethal toxicity , specifically body weight loss, was observed. Calculations using the mean body weight for each treatment against the mean initial body weight (440 mg each) showed that there were body weight gains of 3.3%, 5.3%, 7.7%, 10.5%, 4.6%, and 2.7% for the treatments of 0, 198, 296, 444, 667, 1000 mg/kg dry soil weight. No other toxicity effect was reported. In addition, n o earthworm mortality was obse rved in the water control or in test substance treatments. The 14 day L C 50 was > 1000 mg/kg dw of soil. The 14 day NOEC, based on mortality and body weight, was 1000 mg/kg dw of soil, the highest concentration tested. The CL 377160 is considered to be non
- toxic to earthworms up to a concentration of 1000 mg/kg dw of soil based on this study . However, a freeze storage stability study submitted by

the applicant (PMRA # 1620213) showed that CL 377160 rapidly bound and degraded in soils even at

– 5 oC. Therefo re, the LC 50 obtained from this study is uncertain and the actual L C 50 could be lower. Terrestrial Invertebrates

– Formulation s The terrestrial invertebrate study on honey bees ( A. mellifera , MRID 47267606) classified as supplemental. The study uses a formulation to test toxicity . For honey bee acute contact toxicity

studies, a TGAI test compound is required. Relative to a similar honey bee acute contact toxicity test (MRID 47267508), which shows no mortality at the treatment level (100  g a.i./bee), this formulation appears to be more toxic at a lower nominal concentration (100  g product./bee ≈ 24  g a.i./bee) having 24% mortality . This information suggests that there is something in the formulation that is more toxic than the active ingredient acting al one. Finall y, the concentrations of test substance in the dosing solutions were not determined. Therefore, the actual dose levels used are unknown. The contact test had 2% mortality in the negative and solvent controls and 24% mortality in the 100 μg a.i. /bee level by 48 hours; sub
- lethal effects were 0% in the negative and solvent controls, and 10% in the 100 μg a.i./bee level only at 4 hours but not thereafter. The oral test also had 2 % mort ality in the negative control, 0 % mortali ty in the solvent control, and 4% mortality in the 113.4 μga.i./bee level by 48 hours; sub
- lethal effects were 0% in the negative control, 2% in the solvent control, and 0% in the 113.4 μg a.i./bee level.Page 63 of 114

In a 14 day

acute limit toxicity

study , earthworms (

E. fetida , MRID 4726 7608 ) were exposed to AC 375839 300 g/L SC RLF12359 (SF10358) at 1000 mg formulation/kg dry weight of artificial soil. No concurrent reference chemical test was conducted in this study . The report indicated that the experiment was carried out in accordance with OECD 207. However, only

one concentration was tested which did not fulfill the requirement of the guideline. No earthworm mortality was observed in the water control or in test substance treatment. The 14 day L C 50 was > 1000 mg formulation/kg dry soi l. No significant difference in earthworm burrowing time ( i.e., time needed for 10 earthworms to burrow into the soil after placement on soil surface) was observed at day 7. The average weight loss between Day 0 and Day 14 was 20.6 and 87.9 mg in the test groups of water control and test substance treatment, respectivel y. The difference is statistically significant. The 14 day

NOEC, based on body

weight loss, was < 1000 mg/kg dry soil, the concentration tested. The end
- point toxicity concentration of the te st substance can not be determined from this study ; however, it is considered to be non
- lethal to earthworms up to a concentration of 1000 mg formulation/kg dry soil. No other observable compound related toxicity effect was reported.

T able 26 . Terre strial Invertebrate Acute/Subacute Toxicity Data Comm on Nam e %AI Study param eters LD 50 /NOAEL MRID Classification /Category Technical AC 375839 (a.k.a. BAS 560F) Honey bees Apis M ellifera 95.86 48 hour acute contact and oral toxicity tests 5 reps. / 10 b ees per rep. Contact: 0 (negative, solvent), 100 μg a.i./bee; Oral: 0 (negative, solvent), 114 μg a.i./bee 48 hour contact LD 50 > 100  g ai/bee

NOAEC: 100 μg a.i./bee LOAEC > 100 μg a.i./bee 48 hour oral LC 50 > 114  g ai/bee NOAEC: 114 μg a.i./bee LOAEC > 114 μg a.i./bee 47267508 Acceptable/ Practic ally non - toxic 1

Earthworm Eisenia fetida 95.86 14 day acute limit toxicity 4 reps (treatment); 1 rep (control) / 10 earthworms per rep. Nominal: 1,000 mg a.i./kg dry soil 14 day LC 50 >1,000 mg a.i./kg dry soil

NOAEC < 1,000 mg a.i./kg dry soil LOAEC = 1,0 00 mg a.i./kg dry soil Endpoint(s) affected: possibly we ight loss 47267518 Supplemental/ Non
- GLN 2Page 64 of 114 T able 26 . Terre strial Invertebrate Acute/Subacute Toxicity Data Comm on Nam e %AI Study param eters LD 50 /NOAEL MRID Classification /Category Metabolites Earthworm Eisenia fetida 97 CL 377160 (hydrolytic metabolite of metrafenone) 14 day acute toxicity 4 reps (treatment); 1 rep (control) / 10 earthworms per rep. Nominal: 198, 296, 444, 667, and 1000 mg CL 377160/kg dry soil 14
- day LC 50 >1,000 mg CL377160/kg dry

soil NOAEC: 1,000 mg CL 377160/kg dry soil LOAEC: 1,000 mg CL 377160/kg dry soil Endpoint(s) affected: none. 47267519 Su pplemental/ Non
- GLN 2

Form ulations Honey bees Apis mellifera 24.4%

a.i.; 288 g/L AC 375839 in a

300 g/L SC (SF10358/ RLF12359) 48 hour acute contact and oral toxicity tests 5 reps. / 10 bees per rep. Contact: 0 ( negative, solvent), 100 μg test material 3 /bee; Oral: 0 (negative, solvent), 113.4 μg test material/bee 48 hour contact LD 50 > 100  g form/bee

[>24.4 μg a.i./bee] NOAEC < 100 μg form/bee [< 24.4 μg a.i./bee] LOAEC: 100 μg form/bee [ 24.4 μg a.i./bee] 48 hour oral LC 50 > 113.4  g form/bee [> 27.7 μg a.i./bee] NOAEC: 113.4 μg form/bee [ 27.7 μg a.i./bee] LOAEC > 113.4 μg form/bee [> 27.7 μg a.i./bee] 47267606 Supplemental/ Practically non - toxic 1Page 65 of 114 T able 26 . Terre strial Invertebrate Acute/Subacute Toxicity Data Comm on Nam e %AI Study param eters LD 50 /NOAEL MRID Classification /Category Earthworm Eisenia fetida 288 g

a.i./L AC 375839 300

g/L SC RLF12359 (SF10358) 14 day acute limit toxicity 4 reps (treatment); 1 rep (control) / 10 earthworms per rep. Nominal: 1,000 mg form/kg dry soil 14 day LC 50 >1,000 mg form4/kg dry soil

NOAEC < 1,000 mg form/kg dry soil LOAEC < 1,000 mg form/kg dry soil Endpoint(s) affected: body weight ( i.e. , weight loss) 47267608 Supplemental/ Non
- GLN 2

1 Based on acute contact LD 50 ( g a.i./bee) <2 highly toxic; 2
- 10.99 moderately toxic; ≥11 practically non
- toxic 2 Deemed acceptable by PMRA 3 ‘Test material’ is assumed to mean ‘formulation’ 4 Not enough information provided in the study to determine active ingredient content (2 ) C hronic Effects Birds
- Technical The one - generation reproductive toxicity s tudy ( MRID 47267506) using 20 pairs per level of 12.5
- month old Northern bobwhite quail ( Colinus virginianus ) over 22 weeks. BAS 560F was administered to the birds in the diet at nominal concentrations of 0 (control), 185, 500, or 1350 mg ai/kg diet. M ean - measured concentrations were <3.75 (<LOD, control), 181, 486, and 1320 mg ai/kg diet, respectivel y. No treatment - related effects were observed on an y reproductive parameters at an y concentration level. T here was, however, a significant reduction (p=0.02, 43%) in adult male body w eight gain at the 486 mgai/kg diet level. While this response was not dose
- dependent, similar effects (non
- dose
- dependent) on bird body w eights were observed in the acute avian dietary studies with this test material. T he lack of dose response in this case indicates that both the NOAEC and LOAEC will be ≥1320 mg a.i./kg diet. The one
- generation reproductive toxicity study (MRID 47267507) used 16 pairs per level of ca. 5
- month old mallard duck ( Anas platyrhynchos ) over 22 weeks. BAS 560 F was administered to the birds in the diet at nominal concentratio ns of 0 (control), 450, 900, or 1350 mg ai/kg diet. Mean
- measured concentrations were <18.6 (<LOQ, control), 438, 848, and 1316 mg ai/kg diet, respectivel y. No treatment
- related effects were observed on any adult parameter at any

treatment level, or on any offspring parameter at the 438 and 848 mg ai/kg diet levels. At the 1316 mg ai/kg diet level, a statistically
- significant reduction in the number of eggs laid per hen per week was observed compared to the control (3.3 versus 4.5 eggs/hen/week). Hatcha bility was also reduced at the 1316 mgPage 66 of 114

ai/kg level, where the percentage of chicks “dead
- in
- shell” of fertile eggs increased from 15.7% for the control level to 36.8% for the 1316 mg ai/kg diet level. As a direct result, the percentage of hatched chicks o f fertile eggs was also statistically
- different from the control (57.0 versus 77.0%). The study was deemed supplemental on account of several guideline deviations including lack of reporting for pre
- test mortality, the initial age of the birds was below ( ca. 5 months) recommended age (at least 7 months), and cage size was significantly

smaller than recommended (OPPTS recommends at least 10,000 cm 2 per bird; instead, the floor space was onl y 4225 cm 2 per bird).

Table 27 . Avian Chronic Toxicity Data Comm on Name %AI Study Param eters NOAEC/LOAEC MRID Classification Technical AC 375839 (a.k.a. BAS 560F) Northern Bobwhite Quail Colinus virginianus 95.86 1
- generation reproduction study Pre
- laying exposure 10 weeks; egg laying exposure 12 weeks 2 birds per pe n (1 ♂: 1♀); 20 pens per neg. control and treatment Mean measured: <3.75 (neg. control), 181, 486, and 1320 mg a.i./kg diet NOAEC ≥ 1320 mg a.i./kg diet LOAEC ≥ 1320 mg a.i./kg diet Endpoint(s) affected: none. 47267506 Acceptable

Mallard Duck Anas platyrhynchos 99.4 1
- generation reproduction study Pre
- laying exposure 10 weeks; egg laying exposure 12 weeks 2 birds per pen (1 ♂: 1♀); 20 pens per neg. control and treatment Mean measured: <18.6 (neg. control), 438, 848, and 1316 mg a.i./kg diet NOAEC: = 848 mg a.i./kg diet 1 LOAEC: 1316 mg a.i./kg diet Endpoint(s) affected: egg production (eggs laid per ♀ per w k) and hatchability (% dead
- in
shell of fertile eggs) 47267507 Supplemental

1 Bold value is the value that will be used to calculate risk quotients M ammals

- Technical In a rat 2
- generation reproduction study (MRIDs 46415729, 46415728 ) and given the parental animals, no treatment
- related effects were observed on mortality, clinical signs of toxicity , or macroscopic examinations. The L OAELfor parental toxicity is 1000 ppm (equivalent to 72.8/84.8 mg/kg bw/day [M/F]), based on decreased body weights and body weight gains in the F 1 males. The NOAE L is 500 ppm (equivalent to 35.9/42.9 mg/kg bw/day

[M/F]). Inthe offspring, no effects of treatment were ob served on clinical signs of toxicity , litter parameters, sexual maturation, anogenital distance, hematology , or macroscopic or microscopic pathology
. The LOAELfor offspring toxicity is 10,000 ppm (equivalent to 759/864 mg/kg bw/day [M/F]), based on decrea sed body weights in the F 1 and F 2 pups. The NOAEL is 1000 ppm (equivalent to 72.8/84.8 mg/kg bw/day [M/F]).Page 67 of 114

No effects of treatment were observed on estrous cycle number or length, sperm parameters, primordial follicle count, or reproductive performance. Thus, the LOAEL for reproductive performance was not observed. The NOAEL for reproductive performance is 10,000 ppm (equivalent to 759/864 mg/kg bw/day [M/F]). In a rat developmental toxicity study (MRID 46415726), no treatment
- related effects were obser

ved on mortalities, clinical signs, body weights, body weight gains, food consumption, hematology , liver weights, liver histology , or gross pathology relative to maternal toxicity . Therefore, the maternal LOAEL was not observed. The maternal NOAEL is 1000 mg/kg/day (limit dose). Regarding developmental toxicity : there were no treatment - related effects on the numbers of litters, fetuses (live or dead), resorptions (earl y, late, or complete litter) or on sex ratio or post
- implantation loss, on fetal body wei ghts or on skeletal ossification, indicating no effect on fetal growth or development; there were no treatment
- related external, visceral, or skeletal variations on development or other malformations. Thus, the developmental LOAEL was not observed. The de velopmental NOAEL is 1000 mg/kg/day (limit dose). In a rabbit developmental toxicity study (MRID 46415727), no treatment - related effect was observed on mortalities, hematology , or gross pathology relative to maternal toxicity
. Therefore, the maternal LOAE L is 350 mg/kg/day, based on decreased body weight gains and food consumption; increased liver weights; and increased incidences and/or severity of periportal hepatocellular h ypertroph y and diffuse hepatocellular vacuolation. The maternal NOAEL is 50 mg/k g/day . Regarding developmental toxicity : there were no treatment - related effects on the numbers of litters, fetuses (live or dead), resorptions (earl y, late, or complete litter) or on sex ratio or post
- implantation loss, on fetal body weights or on skeletal ossification, indicating no effect on fetal growth or development; there were no treatment
- related external, visceral, or skeletal variations on development or other malformations. Thus, the developmental LOAEL was not observed. The developmental NOAEL is 700 mg/kg/day
.Page 68 of 114 Table 28 . Mammalian Chronic Toxicity Data Comm on Name %AI Study Param eters NOAEC/ LOAEC MRID Classification/ Category Technical AC 375839 (a.k.a. BAS 560F) Rat 95.86 2
- generation reproduction study 30 CD Sprague
- Dawley rats/sex/group/generation, by feeding (diet)
. 3 treatment groups; 1 untreated diet control group Nominal: 0, 500 1 , 1000, 10000 ppm M: 0, 35.9, 72.8, 759 mg BAS 560 F/kg/day F: 0, 42.9, 84.8, 864 mg BAS 560 F/kg/day Parental systemic NOAEL (M/F): 35.9 /4 2.9 mg/kg bw/day 1 LOAEL (M/F): 72.8/84.8 mg/kg bw /day , based on decreased body wts and body wt gain F 1 males as well as body wts in F 1 and F 2 females Offspring/Develop
mental Toxicity NOAEL (M/F): 72.8/84.8 mg/kg bw /day LOAEL (M/F): 759/864 mg/kg bw /day , based on decreased body wts in F 1 and F 2 pups Reproductive Toxicity NOAEL (M/F): 759/864 mg/kg bw /day LOAEL (M/F): not attained 46415729 46415728 Acceptable /

Guideline

Rat 95.86 Developmental toxicity study 25 rats per dose, by gavage
. 3 treatment groups; 1 untreated control group 0, 50, 500, 1000 mg BAS 560 F/kg/day Maternal NOAEL: 1000 mg/kg/day (HDT; limit dose) LOAEL: not attained Developmental NOAEL: 1000 mg/kg/day (HDT; limit dose) LOAEL: not attained 46415726 Acceptable/ GuidelinePage 69 of 114 Table 28 . Mammalian Chronic Toxicity Data Comm on Name %AI Study Param eters NOAEC/ LOAEC MRID Classification/ Category Rabbit 95 .86 Developmental toxicity study 25 rabbits per group, by gavage
. 3 treatment groups; 1 untreated control group 0, 50, 350, 700 mg BAS 560 F/kg/day Maternal NOAEL: 50 mg/kg/day LOAEL: 350 mg/kg/day, based on decreased body wt gains and food consumption; increased liver wts; increased incidences and/or severity of periportal hepatocellular hypertrophy and diffuse hepatocellular vacuolation Developmental NOAEL: 700 mg/kg/day (HDT) LOAEL: not attained 46415727 Acceptable/ Guideline

1 Bold value is the valu e that will be used to calculate risk quotientsPage 70 of 114

b. Terrestrial Plants The two tier I terrestrial plant studies, seedling emergence (MRID 47267509) and vegetative vigor (MRID 47267510), are both supplemental and are based on the UK/EU formulation (BAS 560 00F, 42.8% purity) . The lower application rates in the studies ( 0.091 and 0.288 lbs a.i./A for the seedling emergence study; and, 0.091 and 0.285 lbs a.i./A for all but soy bean [0.099 and 0.283 lbs a.i./A] for the vegetative vigor study) relative to the label application rate (0.3 lbs a.i./A) leads to uncertainty in the risk characterization especially as effects were noted, but the NOAEC and EC 05 are undefine d. The latter two endpoints are used for endangered species risk calculation s, which cannot be done in this case. Tier II tests are requested to define the latter endpoints , to have a study available that is based on the U.S. formulation, and, subsequently , reduce uncertainty in risk characterization. All species were not signifi cantly affected by

the two treatments in the seedling emergence study. The most sensitive monocot and dicot species could not be determined. The NOAEC for all species (monocot and dicot 5 ) was 0.288 lbs ai/A. The EC 05 , EC 25 >0.288 lbs a.i./A. For the high est treatment level tested, the following effects were noted
-- the % inhibition relative to control that is greater than 5% was observed in the following plants for the given endpoint: emergence (oat, tomato); survival (oat, onion, tomato), dry weight (on ion, ryegrass), and height (cucumber, onion, soy

bean, tomato). All species were not significantly affected by

the two treatments in the vegetative vigor study . The most sensitive monocot and dicot species could not be determined. The NOAEC for all mono cot species was 0.285 lbs ai/A. The EC 05 , EC 25 >0.285 lbs a.i./A. The NOAEC for all dicot species was the same as that for the monocots except for the soy be an 6 which was 0.283 lbs a.i./A (with the EC 05 and EC 25 > 0.283 lbs a.i./A ). For the highest treatment level tested, the following effects were noted
-- the % inhibition relative to control that is greater than 5% was observed in the following plants for the given endpoint: dry

weight (ryegrass) and height ( none ).

5 Monocots incl ude corn, Zea mays ; oat, Avena sativa ; onion, Allium cepa ; and ryegrass, Lolium Perenne ). Dicots include cucumber, Cucumis sativa ; lettuce, Lactuca sativa ; oilseed rape, Brassica napus ; soybean, Glycine max ; sugarbeet, Beta v ulgaris ; and tomato, Lycopersi con esculentum
. 6 Soy bean was treated with the test substance on a different day than the other species, and the concentration of metrafenone in the test substance was analyzed on the same day, thus soybean had a different measured concentration than the o ther test species.Page 71 of 114

IV. Risk Characterization

A. Risk Estima tion

–Integration of Exposure and Effects Data A quantitative estimation of risk integrates EECs and toxicity estimates and evaluates the likelihood of adverse ecological effects to non
- target species. In a deterministic approach, an exposure estimate is divided by a single point estimate of toxicity to calculate a risk quotient (RQ). The RQ is then compared to Agency L evels of Concern (LOCs, Appendix H ), which serve as criteria for categorizing potential risk to non - target organisms and the need to consid er regulatory action.
1. Risk to Aquatic Animals and Plants The greatest amount of uncertainty in the assessment stems from aquatic studies which were largel y based on total concentrations (both dissolved and undissolved) of the test compound. In all cas es (except for the chronic study on the saltwater m ys id, but including aquatic plants), the risk quotient values were not calculated.
a. Aquatic Animals

1. Risk following acute exposure Freshwater Fish and Aquatic
- Phase Amphibians The acute aquatic risk quoti ents (RQs) for freshwater fish and aquatic
- phase amphibians were not calculated. Test compound in solution was not centrifuged and measured (post
centrifugation) in an y of the acute freshwater fish studies (on the technical, metabolites, and formulations) , even though higher concentrations tested exceeded or likely exceeded the solubility

limit of the test compound. Without centrifugation, the amount of chemical that is freel y dissolved and bioavailable cannot be determined. Uncertainty in the level of di ssolved test compound in the solution for all studies renders calculated endpoints suitable for qualitative use only
. Freshwater Invertebrates The acute aquatic risk quotients (RQs) for freshwater invertebrates were not calculated. Test compound in solution was not centrifuged and measured (post
- centrifugation) in an y of the acute freshwater invertebrate studies (on the technical, metabolites, and formulations), even though higher concentrations tested exceeded or likely exceeded the solubility limit of the test compound. Without centrifugation, the amount of chemical that is freel y dissolved and bioavailable cannot be determined. Uncertainty in the level ofPage 72 of 114

dissolved test compound in the solution for all studies renders calculated endpoints suitable for qualitative use only
. Marine/Estuarine Fish The study on the technical active ingredient (MRID 47267446) yielded an LC 50 greater than the highest concentration tested because there were no mortalities and no sublethal effects; therefore, RQs are not repo rted. Marine/Estuarine Invertebrates The acute aquatic risk quotients (RQs) for marine/estuarine invertebrates were not calculated. Test compound in solution was not consistently centrifuged and measured (post
- centrifugation) in any of the acute marine/e stuarine invertebrate studies (on the technical), even though higher concentrations tested exceeded or likel y exceeded the solubility limit of the test compound. Without centrifugation, the amount of chemical that is freel y dissolved and bioavailable cann ot be determined. Uncertainty in the level of dissolved test compound in the solution for all studies renders calculated endpoints suitable for qualitative use only
. 2. Risk following chronic exposure Freshwater Fish and Aquatic
- Phase Amphibians The chron ic aquatic risk quotients (RQs) for freshwater fish and aquatic
- phase amphibians were not calculated. Test compound in solution was not centrifuged and measured (post
- centrifugation) in the chronic freshwater fish study (on the technical), even though high er concentrations tested exceeded or likely exceeded the solubili ty

limit of the test compound. Without centrifugation, the amount of chemical that is freel y dissolved and bioavailable cannot be determined. Uncertainty in the level of dissolved test compo und in the solution for this study renders calculated endpoints suitable for qualitative use only
. Freshwater Invertebrates No acceptable guideline and non
- guideline chronic studies on freshwater invertebrates are available. Therefore, a quantitative es timation of ri sk cannot be conducted. Chronic risk to freshwater invertebrates cannot be precluded. Marine/Estuarine Fish No chronic studies on marine/estuarine fish are available. Therefore, a quantitative estimation of risk cannot be conducted. Chronic risk to marine/estuarine fish cannot be precluded. Marine/Estuarine InvertebratesPage 73 of 114

The chronic aquatic LOC was not exceeded for the proposed use of metrafenone for the technical tested. Table 29 summarizes the RQ values and scenarios used to compare to chronic aquatic LOCs for marine invertebrates. Table 29 . Metrafenone: Chronic Risks to Marine/Estuarine Invertebrates (Application Rate 0.3 lbs a.i./A, 6 Applications/Year) Species Toxicity Endpoint

(μg/L) Scenario 21 - Day EEC (μg/L) Chronic

Risk Quotient 1 Levels of

Concern Exceeded 2 Saltwater mysid Americamysis bahia NOAEC = 22

 g a.i./L Technical Grapes (Metrafenone) NY Grapes CA Grapes 8.82 1.10 0.40

0.05 No

No Saltwater mysid Americamysis bahia NOAEC = 22

 g a.i./L Technical Grapes (Total Metrafenone Residues) NY Grapes CA Grapes 17.67 1.89 0.80

0.09 No

No 1 Chronic Risk Quotients are calculated using the following formula: EEC/NOAEC 2 Chronic LOC for marine/estuarine invertebrates = 1
b. Aquatic Plants The aquatic plant risk quotients (RQs) were not calculated. Test compound in solution was not centrifuged and me asured (post
- centrifugation) in these studies (on the technical, metabolites, and formulations), even though higher concentrations tested exceeded or likely exceeded the solubility

limit of the test compound. Without centrifugation, the amount of chemical that is freel y dissolved and bioavailable cannot be determined. Uncertainty in the level of dissolved test co mpound in the solution for these studies renders calculated endpoints suitable for qualitative use onl y . 2. Risk to Terrestrial Animals and Plants
a. Terrestrial Animals To assess risks of metrafenone to non
- target birds and mammals, EECs and acute and chronic RQs for residues on various forage categories (short grass, tall grass, broadleaf plants/small insects, fruits/pods/large insects, and seeds) w ere obtained from the Tier 1 model, T
- REX v. 1.4.1 for foliar spray applications to the proposed crops. The model assumes initial concentrations on plant surfaces based on Kenaga predicted maximum residues as modified b y Fletcher et al. (1994), and assume s first
- order dissipation. In this case, six applications at 0.3 lbs a.i./A were used.Page 74 of 114

For birds, acute RQs are derived using dose
- based and dietary
- based acute toxicity values. For mammals, acute RQs are derived using a dose
- based acute toxicity valu e, and chronic RQs are derived using a dose
- based chronic toxicity value (the test material was administered b y gavage) and a dietary
- based chronic toxicity value using the standard FDA laboratory rat conversion value provided in the T
- REX model. Dietary
based RQs are calculated using EECs expressed in terms of residue concentration for the various forage categories and toxicity values (LC 50 or NOAEC) expressed in units of dietary concentration. Dose
- based RQs are calculated using a body weight
- adjusted L D 50 and consumption
- weighted equivalent dose sorted by food source and body size. For both birds and mammals, three weight categories (or sizes) are considered.
1. Risk following acute exposure
Birds The acute oral and dietary endpoints are both greater than the highest concentrations tested (>2025 mg a.i./kg bw and >6070 mg a.i./kg diet, respectivel y). There were no mortalities or treatment related clinical signs of toxicity in the acute oral studies; one death in each dietary

study was observed but was not considered treatment related. Therefore, RQ values are not reported. Further discussion will be provided in the risk description. Potential risk to piscivorous birds The potential risk to piscivorous birds considers exposure via consumption of fish contaminated with metrafenone total residues
. However, the acute oral and dietary endpoints are both greater than the highest concentrations tested (>2025 mg a.i./kg bw and >6070 mg a.i./kg diet, respectivel y). There were no mortalities or treatment related clinical signs of toxicity

in the acute oral studies; one death in each dietary study was observed but was not considered treatment related. Therefore, RQ values are not reported. Further discussion will be provided in the risk description. Mammals The acute endpoints for mammals are both greater than the highest concentrations tested (LD 50 : >2000 mg technical/kg bw, mouse; >5000 mg form/kg bw, rat) . There were no mortalities or treatment related clinical signs of toxicity in the acute oral rat stu dy ; one death was observed in the acute oral mouse study. Therefore, RQ values are not reported. Further discussion will be provided in the risk description. Potential risk to piscivorous mammals The potential risk to piscivorous mammals considers expos ure via consumption of fish contaminated with metrafenone total residues
. However, the mammalian acute endpointsPage 75 of 114

are both greater than the highest concentrations tested (LD 50 : >2000 mg technical/kg bw, mouse; >5000 mg form/kg bw, rat). A male mouse died in the acute oral mouse study (MRID 47267522) on the technical; there were no mortalities in the acute oral rat study (MR ID 47267609) on the formulation. Therefore, RQ values are not reported. Further discussion will be provided in the risk description.

T errestrial invertebrates Metrafenone is classified as ‘practicall y non - toxic’ to honey bees on an acute contact basis, based on available data for the TGAI and formulation (24.4% a.i.). Given a non
guideline acute earthworm study using the technical activ e ingredient, metrafenone is considered to be non
- lethal to earthworms up to a concentration of 1000 mg a.i./kg dry soil. Similarly , given a non
- guideline acute earthworm study using a metrafenone metabolite, the metabolite too is considered to be non
- leth al to earthworms up to a concentration of 1000 mg/kg dry weight of soil. In addition, given a non
- guideline acute earthworm study using a formulation, the formulation is also considered to be non
- lethal to earthworms up to a concentration of 1000 mg formul ation/kg dry soil. Additional discussion is provided in the risk descriptio n section. 2. Risk following chronic exposure
Birds Utilizing the chronic endpoint (848 mg a.i./kg diet) from a 1
- generation reproduction study (MRID 47267507) conducted with mallard duck and the T
- REX model v.1.4.1, the chronic avian dietary
- based RQs do not exceeded the chronic LOC for birds for an y food category
.
Table 30 . Upper Bound Kenaga, Chronic Avian Dietary Based Risk Quotients Grapes: 0.3 lbs a.i./A; 6 Applications/sea son

NOAEC (ppm) EECs and RQs 1,2 ,3

Short Grass Tall Grass Broadleaf Plants/ Sm all Insects Fruits/Pods/ Seeds/ Large Insects EEC RQ EEC RQ EEC RQ EEC RQ 181 241.01 0.28 110.46 0.13 135.57 0.16 15.06 0.02 1 Risk Quotients are calculated using the follo wing formula: EEC / NOAEC 2 Chronic risk LOC = 1 3 Based on avian chronic NOAEC = 848 mg a.i./kg dietPage 76 of 114 Potential risk to piscivorous birds The potential risk to piscivorous birds considers exposure via consumption of fish contaminated with metrafenone total residues . None of the RQs exceed the chronic LOC for birds. The following table provides estimated RQs from KABAM using the maximum application rate and the scenario yi elding the highest aquatic EECs (New York Grapes scenario; metrafenone total res idue and high runoff scenario).

Table 31 . Chronic RQ values for Birds Consuming Fish Contaminated by Me trafenone (based on KABAM) 1 Wildlife Species Dose Based Dietary Based 2,3 sandpipers N/A 0.016 cranes N/A 0.016 rails N/A 0.018 herons N/A 0.019 small osprey N/A 0.022 white pelican N/A 0.023 N/A = Not applicable 1 NY Grapes scenario (at 0.3 lbs a.i./A with 6 applications/year) 2 Ba sed on avian chronic NOAEC = 848 mg a.i./kg diet 3 LOC for chronic risk = 1.0 Mammals The chronic LOC is exceed ed on a dose basis for mammals in all size classes eating short grass, for the 15 and 35 gram size classes eating tall grass and broadleaf plants / small insects. The chronic LOC on a dietary basis is not exceeded for any of the food categories. Risks to mammals following chronic exposure will be further discussed in the risk description section. Table 32 . Upper Bound Kenaga, Chronic Mammalian Dietary Based Risk Quotients Grapes: 0.3 lbs a.i./A; 6 Applications/season
NOAEC (ppm) EECs and RQs 1,2 , 3

Sh ort Grass Tall Grass Broadleaf Plants/ Sm all Insects Fruits/Pods/

Seeds/ Large Insects EEC RQ EEC RQ EEC RQ EEC RQ 500 241.01 0.48 110.46 0.22 135.57 0.27 15.06 0.03 1 Risk Quotients are calculated using the following formula: EEC / NOAEC 2 Chronic ris k LOC = 1 3 Based on mammalian chronic dietary NOAEL: 500 mg/kg dietPage 77 of 114

Table 33 . Upper Bound Kenaga, Chronic Mammalian Dose - Based Risk Quotients

Size Class (gram s) Adjusted

NOAEL EECs and RQs 1,2 , 3

Short Grass Tall Grass Broadleaf Plants/ Sm all Ins ects Fruits/Pods/

Seeds/ Large Insects Granivore EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ 15 78.90 229.78 2.91 4 105.32 1.33 129.25 1.64 14.36 0.18 3.19 0.04 35 63.84 158.81 2.49 72.79 1.14 89.33 1.40 9.93 0.16 2.21 0.03 1000 27.61 36.82 1.33 16.88 0.61 20. 71 0.75 2.30 0.08 0.51 0.02 1 Risk Quotients are calculated using the following formula: EEC / NOAEC 2 Chronic risk LOC = 1 3 Based on mammalian chronic dose
- based NOAEL: 35.9 mg/kg bw/day 4 Bolded values exceed LOC Potential risk to piscivorous mamma ls The potential risk to piscivorous mammals considers exposure via consumption of fish contaminated with metrafenone total residues . None of the RQs exceed the chronic LOC for mammals. The following table provides estimated RQs from KABAM using the max imum application rate and the scenario yi elding the highest aquatic EECs (New York Grapes scenario; metrafenone total residue and high runoff scenario). Table 34 . Chronic RQ Values for Mamm als Consuming Fish Contaminated by Me trafenone (based on KABAM) 1 Wildlife Species Dose Based 2,3 Dietary Based 2,3 fog/water shrew 0.103 0.019 rice rat/star
- nosed mo le 0.125 0.018 small mink 0.159 0.025 large mink 0.176 0.025 small river otter 0.189 0.025 large river otter 0.219 0.027 1 NY Grapes scenario (at 0. 3 lbs a.i./A with 6 applications/year) 2 Based on mammalian chronic NOAEC = 35.9 mg/kg bw/day 3 LOC for chronic risk = 1.0Page 78 of 114 b. Terrestrial Plants Terrestrial plant risk quotients were not calculated on account of indeterminate endpoints generated in both the seedling emergence and vegetative vigor studies.

B. Risk Description Based on the available ecotoxicity data and predicted environmental exposures, this ecological risk assessment supports the presumption of risk to mammals following chronic exposure
. 1. Risk to Aquatic Animals and Plants a. Aquatic Animals

1. Risk following acute exposure Freshwater Fish and Aquatic
- Phase Amphibians Technical The metrafenone limit of water solubility is approximately

0.2
- 0.5 mg/L at 12 o C . The acute rainbow trout study (M RID 47267443) indicated only 5% mortality

at levels below (0.065 mg total a.i./L) and above (0.43 and 0.82 mg total a.i./L) the solubility limit, which implies the effect may not be dose related; 16% of fish were lethargic and 5% exhibited dark discolorati on after 96 hours only at the highest concentration tested (0.82 mg total a.i./L). The acute bluegill sunfish stu dy (MRID 47267442) indicated 15 % mortality , 18% lethargic fish, and 12% virtuall y immobile but respiring fish at the highest concentration test ed (0.87 mg total a.i./L) after 96 hours . Given that the test solution was not centrifuged, the amount of actual dissolved active ingredient potentially leading to the observed effects is unknown. Nevertheless, given these studies and assuming that metrafe none concentrations in the environment reach the solubility limit, the effect of the technical grade active ingredient on freshwater fish is likely to be low. However , according to the model estimated EECs (0.00153
- 0.02 mg/L, which includes metrafenone and total metrafenone residue scenarios), levels of metrafenone at the solubility limit are not expected to occur in the environment given the proposed grape use. Therefore, acute risk to freshwater fish and aquatic
- phase amphibians is not expected as a res ult of metrafenone use on grapes given the results from the studies using technical grade active ingredient. Metabolites/Degradates The limits of water solubility for metabolites of metrafenone were not reported in the available studies ; exceedance of so lubility limit for a given metabolite (Reg. No. 4084564) was assumed given observed undissolved test substance in all five treatment groups of one acute study (MRID 47267445) . The acute rainbow trout study (MRID 47267444) was a limit test with no effects n oted at 99 mg total a.i./L . Another acutePage 79 of 114

rainbow trout study

(MRID 47267445) indicated 80% mortality at 20.3 mg total a.i./L and 100% mortality

at 35.2 an d 58.4 mg total a.i./L; sublethal effects were observed in the three highest concentrations: 20.3 mg total a.i./L(tottering, apathy , and distended abdomen), 35.2 mg total a.i./L(apathy and distended abdomen), and 58.4 mg total a.i./L (tottering and distended abdomen). Given that the test solution was not centrifuged, the amount of actual dissolved metab olite potentially leading to the observed effects is unknown. According to the model estimated EECs (0.00225
- 0.02 mg/L, which includes total metrafenone residue scenarios), levels of metrafenone metabolites at the tested levels are not expected to occur in the environment given the proposed grape use. Therefore, the effect of metrafenone metabolites on freshwater fish is likely to be low. Formulations The metrafenone limit of water solubility is approximately

0.2
- 0.5 mg/L at 12 o C . The acute study (MRID 4 7267605) using a formulation (BAS 560 00F, SF 10358, RLF 12359) indicated no effects on rainbow trout at concentrations above the solubility limit, from 3.0 to 23.3 mg total a.i./L . Given that the test solution was not centrifuged, the amount of actual dis solved active ingredient is unknown. Not unlike the conclusion drawn for the technical active ingredient, given this study and assuming that metrafenone concentrations in the environment reach the solubility limit, the effect of this particular formulation on freshwater fish is likely to be low. However , according to the model estimated EECs (0.00153
- 0.02 mg/L, which includes metrafenone and total metrafenone residue scenarios), levels of metrafenone at the solubility limit are not expected to occur in th e environment given the proposed grape use. Although this EU/UK formulation closely matches the U.S. formulation ( i.e. , BAS 560 03F) it is still not its equivalent. Therefore, the effect of the U.S. formulated product on freshwater fish and aquatic
- phase amphibians is not known. Freshwater Invertebrates Technical The metrafenone limit of water solubility is approximately

0.2
- 0.5 mg/L at 12 o C. The acute study (MRID 47267437), in which the three highest concentrations (0.22, 0.45, and 0.92 mg total a.i./L) were at or above the solubility limit, indicated no effects on daphnia. Given that the test solution was not centrifuged, the amount of actual dissolved active ingredient is unknown. Nevertheless, given this study and assuming that metrafenone concentratio ns in the environment reach the solubility limit, the effect of the technical grade active ingredient on freshwater invertebrates is likely to be low. However, according to the model estimated EECs (0.00153
- 0.02 mg/L, which includes metrafenone and total metrafenone residue scenarios), levels of metrafenone at the solubility limit are not expected to occur in the environment given the proposed grape use. Therefore, acute risk to freshwater invertebrates is not expected as a result of metrafenone use on gr apes given the results from the studies using technical grade active ingredient.Page 80 of 114

Metabolites/Degradates The limits of water solubility for metabolites of metrafenone were not reported in the available studies
. The acute daphnia study (MRID 47267438 ) with CL375816 indicated no effects. Another acute daphnia study (MRID 47267439 ) indicated 5, 55, and 65% immobility

at the three highest concentrations 23.2, 49.6, and 66.4 mg total a.i./L , respectivel y, after 48 hours (test termination). Given that the test solution was not centrifuged, the amount of actual dissolved metabolite potentially leading to the observed effects is unknown. According to the model estimated EECs (0.00225
- 0.02 mg/L, which includes total metrafenone residue scenarios), levels of metrafenone metabolites at the tested levels are not expected to occur in the environment given the proposed grape use. Therefore, the effect of metrafenone metabolites on freshwater invertebrates is likely to be low. Formulations The metrafenone limit of wat er solubility is approximately

0.2
- 0.5 mg/L at 12 o C . The acute study (MRID 47267604 ) using a formulation (BAS 560 00F, SF 10358, RLF 12359) indicated 65 and 90% mortality at the two highest concentrations 6.0 and 11.6 mg total a.i./L , respectivel y, at 48 h ours (test termination); 5% immobility was observed in the negative control, 0.76 and 1.5 mg total a.i./L concentrations, 15% at 3.0 mg total a.i./L , and 25% at 6.0 mg total a.i./L . Given that the test solution was not centrifuged, the amount of actual dis solved active ingredient potentially leading to the observed effects is unknown. Not unlike the conclusion drawn for the technical active ingredient, given this study and assuming that metrafenone concentrations in the environment reach the solubility limi t, the effect of this particular formulation on freshwater invertebrates is potentially low. However, according to the model estimated EECs (0.00153
- 0.02 mg/L, which includes metrafenone and total metrafenone residue scenarios), levels of metrafenone at the solubility limit are not expected to occur in the environment given the proposed grape use. Although this EU/UK formulation closely matches the U.S. formulation ( i.e. , BAS 560 03F) it is still not its equivalent. Therefore, the effect of the U.S. formu lated product on freshwater invertebrates is not known.
Marine/Estuarine Fish The study on the technical active ingredient (MRID 47267446) yielded an LC 50 greater than the highest concentration tested because there were no mortalities and no suble thal e ffects; therefore, RQs were not reported. Comparison of the peak aquatic EECs ( 0.02 m g/ L , taken from the total metrafenone residue scenario ) with the highest concentration tested (0.65 mg a.i./Luncentrifuged; 0.35 mg a.i./L centrifuged) shows that the EEC s were at least 17 times less than the highest concentrations tested in the studies. Therefore, acute risk to marine/estuarine fish is not expected as a result of metrafenone use on grapes . Marine/Estuarine InvertebratesPage 81 of 114

The metrafenone limit of water so lubility is approximately

0.2
- 0.5 mg/L at 12 o C. The acute eastern o ys ter study (MRID 47267440) indicated effects on shell deposition, whereb y relative to the negative control the mean percent reduction in shell growth starting with the negative solvent (th en, 0.0522, 0.104, 0.203, 0.287 mg total a.i./L , and 0.33 mg dissolved a.i./L) is as follows: 17.4, 13.9, 26.3, 44.3, 84.2, and 100%, respectivel y . Therefore, should concentrations in the environment reach the solubility limit, the acute risk to marine/est uarine invertebrates may

be expected. However, given that the test solution was not centrifuged for all but the highest test concentration , the amount of actual dissolved active ingredient potentially leading to the observed effects is unknown. Meaning that interpretation of effects from total concentrations cited here may underestimate potential risk. Similarly , the acute saltwater m ys id study (MRID 47267441) indicated a dose related effect, this time on mortality at the four out of five highest concentrat ions: 5% at 0.129 and 0.240 mg total a.i./L , 15% at 0.416 mg total a.i./L , and 95% at 0.663 mg total a.i./L ; in addition, erratic swimming was observed in the two highest concentrations by test termination. Despite the dose response, without centrifugation , the amount of chemical that is freely dissolved and bioavailable cannot be determined and, again, interpretation of effects from total concentrations cited here may underestimate potential risk. However, according to the model estimated EECs (0.00153
- 0 .02 mg/L, which includes metrafenone and total metrafenone residue scenarios), levels of metrafenone at the solubility limit are not expected to occur in the environment given the proposed grape use. Given these studies and assuming that metrafenone concentrations in the environment are not likel y to reach the solubility limit, the acute risk to marine/estuarine invertebrates is not expected.

2. Risk following chronic exposure Freshwater Fish and Aquatic
- Phase Amphibians The metrafenone limit of water solubility is approximately

0.2
- 0.5 mg/L at 12 o C. The chronic fathead minnow study (MRID 47267449) indicated post
- hatch survival (28
- day s post - hatch) was statistically
- reduced compared to the negative control at the three highest concentrations 0. 227, 0. 421, and 0.839 m g total a.i./L(p ≤0.05). Post
- hatch survival averaged 96% at the negative control through 0.118 m g total a.i./L levels, and 87, 86, and 11% at the 0. 227, 0. 421, and 0.839 m g total ai/L levels, respectivel y. Therefore, a dose response is evident and implies that should concentrations in the environment reach the solubility limit, the chronic risk to freshwater fish may be expected . No clinical signs of toxicity were observed during the study in an y treatment group. Fish length was significantl y reduced relative t o the average negative control length at the two highest concentrations 0. 421 and 0. 839 m g total ai/L and wet and dry weight were significantl y lower than the negative control weights at the highest concentration ( 0.839 m g total a
. i
. /L level); however, significant impact on survival occurred at these levels. Given that the test solution was not centrifuged, the amount of actual dissolved active ingredient potentially

leading to the observed effects is unknown. For example, the NOAEC value is low (0.118 mg t otal a.i./L) even though the measured concentration includes dissolvedPage 82 of 114

and undissolved substance, but had the sample been centrifuged

– including the dissolved compound only
- the value would likely be lower. Therefore, conclusions drawn from these data wo uld lead to an underestimation of potential risk. According to the model estimated EECs (0.00075
- 0.017 mg/L, which includes metrafenone and total metrafenone residue scenarios), levels of metrafenone at the solubility limit are not expected to occur in the environment given the proposed grape use
. Assuming that metrafenone concentrations in the environment are not likely to reach the solubility

limit or the concentrations used in this study7 , the chronic risk to freshwater fish and aquatic
phase amphibian s is not expected.
Freshwater Invertebrates No acceptable chronic ecotoxicity studies on freshwater invertebrates are available
. Chronic risk to freshwater invertebrates cannot be precluded. Marine/Estuarine Fish No chronic ecotoxicity

studies on es tuarine/marine fish have been submitted to the Agency for review. Chronic risk to estuarine/marine fish cannot be precluded. Marine/Estuarine Invertebrates The chronic aquatic LOC was not exceeded for the proposed use of metrafenone for the technical ac tive ingredient (MRID 47267448) tested on the marine/estuarine invertebrate (saltwater m ys id); no data is available for metabolites or formulation studies on marine/estuarine invertebrates. Although reproduction (number of offspring per female per reproduc tive day) was the (most sensitive) affected endpoint in this study , yielding a definitive endpoint , the RQ calculations indicate that chronic risk to marine/estuarine invertebrates is not expected as a result of metrafenone use. b. Aquatic Plants
For all a quatic plant studies, dissolved or soluble concentrations ( i.e. , post - centrifugation) of test material were not determined. Without centrifugation, the amount of chemical that is freel y dissolved and bioavailable cannot be determined. This is especially a problem as some of the testing concentrations were conducted above the solubility limit of the technical grade active ingredient (MRID 47267511, 47267512, 47267513, 47267514, 47267515, technical; MRID 47267607, formulation) . In addition, the metabolite solubility limit is unknown which leads to uncertainty in interpreting the measured concentrations in the metabolite studies (MRID 47267516, 47267517)
. The lowest

7 The acute eastern oyster study (MRID 47267440) using the technical grade active ingredient indicated a 42% reduction in concentration from uncentrifuged sample to centrifuged sample. If the percentage is applied to the NOAEC value from this study, 0.118 mg total a.i./L, it would reduce to 0.068 mg a.i./L, which is still above the highest model estimated EEC value (0.02 mg/L).Page 83 of 114

concentration tested among the vascular plants ( MRID 47267511, L. gibba : 0.057 mg total a.i./L ; or, 0.033 mg a.i./Lassuming a 42% reduction after h ypothetical centrifugation 8 ) and non - vascular plants ( MRID 47267513, S. costatum : 0.0509 m g total a.i./L ; or 0.0295 mg a.i./L 9 ) is higher than the highest peak aquatic EEC value of 0.0 2 m g/ L (assuming th e total metrafenone residue scenario)
. T he refore, had valid endpoints ( i.e. , those based on dissolved concentrations) been determined using these studies, they would likely

be greater than the highest model predicted concentration in the environment, which implies that risk to vascular and non - vascular species is not expected as a result of metrafenone use on grapes . Although the EU/UK formulation used in one of the studies closely

matches the U.S. formulation ( i.e. , BAS 560 03F) it is still not its equival ent. Therefore, the effect of the U.S. formulated product on vascular and non
vascular aquatic plants is not known.
2. Risk to Terrestrial Animals and Plants a. Terrestrial Animals

1. Risk following acute exposure Birds The acute oral and dietary endpoints are b oth greater than the highest concentrations tested (>2025 mg a.i./kg bw and >6070 mg a.i./kg diet, respectivel y). There were no mortalities or treatment related clinical signs of toxicity in the acute oral studies; one death in each dietary

study was obser

ved but was not considered treatment related. As a result, RQ values were not reported. Toxicity characterization implies that the technical is practicall y non - toxic. In addition, the highest concentration tested for the oral studies (2025 mg a.i./kg bw) i s 7 times higher than the highest dose
- based EEC (274.49 mg/kg) calculated from T
- REX; meanwhile, the highest concentration tested for the dietary studies (6070 mg a.i./kg diet) is 25 times higher than the highest dietary
- based EEC (241.01 mg/kg). Therefor e, given that comparison, acute risk to birds is not expected as a result of metrafenone use. Potential risk to piscivorous birds Several characteristics of metrafenone indicate that it has the potential to accumulate in tissues of aquatic organisms. Th e l og of the n - octanol/water partition coefficient for metrafenone is 4.3 (at 25 o C, pH 4). The lipid normalized BCF was determined to be between 140 and 530 (se e MRID 47267450)
. As stated in the risk estimation section, the acute oral and dietary endpoint s are both greater than the highest concentrations tested (>2025 mg a.i./kg bw and >6070 mg a.i./kg diet, respectivel y). There were no mortalities or treatment related clinical signs of toxicity in the acute oral studies; one death in each dietary study wa s observed but was not considered treatment related. As a result, RQ values were not reported. The highest concentration tested for the oral studies (2025 mg a.i./kg bw) is 147 times higher than the

8 See eastern oyster study (MRID 47267440) 9 See eastern oyster study (MRID 47267440)Page 84 of 114

highest dose
- based EEC (13.73 mg/kg bw/day) calculated from KABAM for birds consuming fish contaminated b y metrafenone total residues ; meanwhile, the highest concentration tested for the dietary studies (6070 mg a.i./kg diet) is 310 times higher than the highest dietary
- based EEC (19.59 mg/kg). Therefore, given that comparison, acute risk to piscivorous birds is not expected due to consumption of fish contaminated with metrafenone. Mammals There were no mortalities in the acute oral rat study (MR ID 47267609) on the formulation; one death was observed in the acute oral mouse study (MRID 47267522) on the technical active ingredient
. Although the EU/UK formulation used in the formulation study closel y matches the U.S. formulation ( i.e. , BAS 560 03F) it is still not its equivalent. Therefore, the effect of the U.S. formulated product on mammals is not known. The acute endpoints for mammals are both greater than the highest concentrations tested (LD 50 : >2000 mg technical/kg bw, mouse; >5000 mg form/kg bw, rat) . Therefore, RQ values were not reported. Inthe mouse s tudy , onl y 3 individuals/sex were tested with mortality in 1/6 animals (17%). With a larger test sample, the LD 50 could be approached. The toxicity

classification implies that the technical is practicall y non - toxic to mice. In addition, the highest concentration tested for the oral study (2000 mg a.i./kg bw) is 9 times higher than the highest dose
- based EEC (229.78 mg/kg) calculated from T
- REX. Therefore, given that comparison, acute risk to mammals is not expected as a result of metrafenone use. Potentia l risk to piscivorous mammals Risk to piscivorous mammals via consumption of fish contaminated with metrafenone was assessed because metrafenone has the potential to accumulate in tissues of aquatic organisms
. As stated in the risk estimation section, there were no mortalities in the acute oral rat study (MR ID 47267609) on the formulation and there was only one death in the acute oral mouse study

(MRID 47267522) o n the technical
. Although the EU/UK formulation used in the formulation study matches the U. S. formulation ( i.e. , BAS 560 03F) it is still not its equivalent. Therefore, the effect of the U.S. formulated product on mammals is not known. The highest concentration tested for the oral studies (2000 mg a.i./kg bw) is 257 times higher than the highes t dose
- based EEC (7.795 mg/kg bw/day) calculated from KABAM for mammals consuming fish contaminated b y metrafenone total residues . Therefore, given that comparison, acute risk to piscivorous mammals is not expected due to consumption of fish contaminated w ith metrafenone.Page 85 of 114

Terrestrial invertebrates The 48
- hour contact LD 50 is >24.4 μg a.i./bee [>100 μg form/bee] with a NOAEC of <24.4 μg a.i./bee and a LOAEC of 24.4 μg a.i./bee based on mortality. Based on this toxicity data, metrafenone is classified as ‘ practically non - toxic’ to honey

bees on an acute contact basis. Thus, risk to honey bees is not expected as a result of direct contact with metrafenone. Similarly , the non
- guideline earthworm studies consider metrafenone, its degradate, and a formulation t o be non
- lethal to earthworms up to a concentration of 1000 mg a.i./kg dry

soil, 1000 mg/kg dry

weight of soil, and 1000 mg formulation/kg dry soil, respectivel y. E. fetida is found in topsoil at depths of approximately 5
- 20cm. Given a soil depth of 20 cm and assuming a maximum application rate per season (1.8 lbs a.i./A, which assumes a h ypothetical maximum active ingredient loading rate since the seasonal rate would not be applied all at once and likel y degrade if applied in the recommended 6 applications of at most 0.3 lbs a.i./A ), the EEC is much lower (0.77 mg/kg soil) than the concentrations generated in these studies. At shallower depths (5 cm), the EEC is higher (3.08 mg/kg soil), but still lower than the study concentration (1000 mg a.i./kg soil). T herefore, risk to earthworms is not expected as a result of metrafenone use on grapes. Although the EU/UK formulation used in the formulation studies for the bee and earthworm matches the U.S. formulation ( i.e. , BAS 560 03F) it is still not its equivalent. Therefore, the effect of the U.S. formulated product on bees (and earthworms) is not known.

2. Risk following chronic exposure Birds The chronic avian dietary
- based RQ does not exceed the chronic LOC for bird s for an y food catogory . The study (MRID 47267 507 ) was done on mallard duck using the technical grade and yi elded a definite endpoint based on egg production (eggs laid per female per week) and hatchability (% dead
- in
- shell of fertile eggs) . Due to the fact that the RQ is only

based on one bird specie s, there is an uncertainty associated with the estimated risk for all avian species. Nevertheless, given that LOC s were not exceeded, chronic risk to birds is not expected as a result of metrafenone use on grapes . Potential risk to piscivorous birds As previously

stated, risk to piscivorous birds via consumption of fish contaminated with metrafenone was assessed because metrafenone has the potential to accumulate in tissues of aquatic organisms
. As stated in the risk estimation section, none of the RQs exceed the chronic LOC for birds. Therefore, chronic risk to piscivorous birds is not expected due to consumption of fish contaminated with metrafenone total residues
. MammalsPage 86 of 114

The chronic LOC is exceeded on a dose basis for mammals in all size classes eating short grass, for the 15 and 35 gram size classes eating tall grass and broadleaf plants / small insects. The chronic LOC on a dietary basis is not exceeded for any of the food categories. The study (MRID 46415729, 46415728) was done on the rat usi ng the technical grade and yi elded a definite endpoint based on decreased body weights and body weight gain in F 1 males as well as body weights in F 1 and F 2 females. Due to the fact that the RQ is only

based on one mammalian species, there is an uncertainty associated with the estimated risk for all mammals. Nevertheless, given the LOC exceedance chronic risk to mammals is expected as a result of metrafenone use. To reduce chronic risk to mammals, several components of the application protocol would have to change. For example, in o rder to have no chronic LOC exc eedances ( i.e. , all RQs < 1) for mammals, the minimum single application rate (0.2 lbs a.i./A) would have to be cut by 25% ( i.e. , to 0.15 lbs a.i./A) ye t considered the maximum instead , the applicati on interval would have to nearly double (from 14 days up to 26 day s), and the maximum allowed number of applications would have to be cut from 6 to 5. Alternatively , in order to have no chronic LOC exceedances for mammals, the minimum single application rate (0.2 lbs a.i./A) can still be applied yet considered the maximum instead , but the application interval would have to nearly double (from 14 day s up to 26 day s), and the maximum number of applications would have to be cut b y 50% ( i.e. , from 6 to 3). Furthermore, in order to have no chronic LOC exceedances in nearl y all cases for mammals

–the one exception being an exceedance for the 15g size glass consuming short grass where the calculated RQ is 1.02

– the minimum single application rate (0.2 lbs a.i./A) would be changed to the maximum single application rate and the ap plication interval (14 day s) could remain as currentl y prescribed by the label, but the maximum number of applications would have to be reduced from 6 to 2. Potential risk to piscivorous ma mmals As previously

stated, risk to piscivorous mammals via consumption of fish contaminated with metrafenone was assessed because metrafenone has the potential to accumulate in tissues of aquatic organisms
. As stated in the risk estimation section, none of the RQs exceed the chronic LOC for mammals. Therefore, chronic risk to piscivorous mammals is not expected due to consumption of fish contaminated with metrafenone
. b. Terrestrial Plants As stated in the risk estimation section, terrestrial plant ris k quotients were not calculated on account of indeterminate endpoints generated in both the seedling emergence and vegetative vigor studies. The lower application rates in the studies (0.091 and 0.288 lbs a.i./A for the seedling emergence study; and, 0.091 and 0.285 lbs a.i./A for all but soy bean [0.099 and 0.283 lbs a.i./A] for the vegetative vigor study) relative to the label application rate (0.3 lbs a.i./A) leads to uncertainty in the risk characterization especiall y as effects were noted. However, the effects in both studies are not considered significant and the NOAEC and EC 05 are undefined (seedling emergence: NOAEC 0.288 lbs a.i./A; EC 05 , EC 25 > 0.288 lbs a.i./A; vegetative vigor: NOAEC 0.285 lbs a.i./A; EC 05 , EC 25 >Page 87 of 114

0.285 lbs a.i./A 10 ). Consequently , the most sensitive monocot and dicot species could not be determined from either study
. Hy pothetically , had the NOAEC been determined to be 0.091 lbs a.i./A (the lower concentration tested) in both the vegetative vigor and seedling emergence studies and g iven the maximum single application rate (0.3 lbs a.i./A), the risk would not have triggered concern for either the dicot or monocot species. In addition, the EECs based on the maximum seasonal application rate (1.8 lbs a.i./A) range from 0.018

– 0.198 lbs a.i./A, which are below the concentrations tested in these studies. Since effects were not significant at the test concentrations, which are higher than the calculated EECs, risk to terrestrial plants is not expected as a result of use of the EU/UK formul ation . B oth studies were conducted on the EU/UK formulation (BAS 560 00F); therefore, uncertainty exists in determining risk to the U.S. formulation (BAS 560 03F)
. Tier II tests are requested to better define the toxicity endpoints , to have a study availab le that is based on the U.S. formulation, and, subsequently , reduce unce rtainty in risk characterization
. 3. Review of Incident Data With the proposed use on grapes, metrafenone will be applied in the United States for the first time. Therefore, no incide nt data are available at this time. 4. Endocrine Effects As required under FFDCA section 408(p), EPA has developed the Endocrine Disruptor Screening Program (EDSP) to determine whether certain substances (including pesticide active and other ingredients) m ay have an effect in humans or wildlife similar to an effect produced b y a “naturally occurring estrogen, or other such endocrine effects as the Administrator may

designate.” The EDSP employ s a two - tiered approach to making the statutorily

required determ inations. Tier 1 consists of a battery of 11 screening assay s to identify the potential of a chemical substance to interact with the estrogen, androgen, or thy roid (E, A, or T) hormonal sy stems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal s ys tems will proceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests are necessary

based on the available data. Tier 2 testing is designed to identify any adv erse endocrine related effects caused by the substance, and establish a dose
- response relationship between the dose and the E, A, or T effect. Between October 2009 and February 2010, EPA is issuing test orders/data call
- ins for the first group of 67 chemi cals, which contains 58 pesticide active ingredients and 9 inert ingredients. This list of chemicals was selected based on the potential for human exposure through pathway s such as food and water, residential activity , and certain post
application agricul tural scenarios. This list should not be construed as a list of known or likely endocrine disruptors.

10 Applicable to all dicot (and monocot) species except for the soybean for which the endpoints are NOAEC 0.283 lbs a.i./A and EC 05 , EC 25 > 0.283 lbs a.i./A in the vegetative vigor study only.Page 88 of 114

Metrafenone is not among the group of 58 pesticide active ingredients on the initial list to be screened under the EDSP. Under FFDCA sec. 408(p) the Ag ency must screen all pesticide chemicals. Accordingl y, EPA anticipates issuing future EDSP test orders/data call
- ins for all pesticide active ingredients
. For further information on the status of the EDSP, the policies and procedures, the list of 67 che micals, the test guidelines and the Tier 1 screening battery , please visit our website: http://www.epa.gov/endo/. 5. Federally Threatened and Endangered (Listed) Species Section 7 of the Endangered Species Act, 16 U.S.C. Section 1536(a)(2), requires all fe deral agencies to consult with the National Marine Fisheries Service (NMFS) for marine and anadromous listed species, or the United States Fish and Wildlife Services (FWS) for listed wildlife and freshwater organisms, if they are proposing an "action" that may affect listed species or their designated habitat. Each federal agency is required under the Act to insure that an y action they authorize, fund, or carry out is not likely to jeopardize the continued existence of a listed species or result in the des truction or adverse modification of designated critical habitat. To jeopardize the continued existence of a listed species means "to engage in an action that reasonably would be expected, directly or indirectl y, to reduce appreciabl y the likelihood of both the survival and recovery of a listed species in the wild by reducing the reproduction, numbers, or distribution of the species" (50 C.F.R. § 402.02). To facilitate compliance with the requirements of the Endangered Species Act (subsection (a)(2)), the Office of Pesticide Programs has established procedures to evaluate whether a proposed registration action may directl y or indirectly reduce appreciably

the likelihood of both the survival and recovery of a listed species in the wild by reducing the reprod

uction, numbers, or distribution of any listed species (USEPA, 2004). After the Agency’s screening level risk assessment is conducted, if any of the Agency ’s listed species LOCs are exceeded for either direct or indirect effects, an anal ys is is conducted to determine if an y listed or candidate species may co
- occur in the area of the proposed pesticide use or areas downstream or downwind that could be contaminated from drift or runoff/erosion. If listed or candidate species may be present in the proposed a ction areas, further biological assessment is undertaken. The extent to which listed species may

be at risk then determines the need for the development of a more comprehensive consultation package as required by the Endangered Species Act. Both acute en dangered species and chronic risk LOCs are considered in the screening
level risk assessment of pesticide risks to listed species. Endangered species acute LOCs are a fraction of the non
- endangered species LOCs or, in the case of endangered plants, RQs are derived using lower toxicity endpoints than non
- endangered plants. Therefore, concerns regarding listed species within a taxonomic group are triggered in exposure situations where restricted use or acute risk LOCs are triggered for the same taxonomic gro up. The risk assessment also includes an evaluation of the potential probability of individual effects for exposures that may occur at the established endangered speciesPage 89 of 114

LOC both in the risk characterization and the endangered species sections. This prob ability

is calculated using the established dose/response relationship and assumes a probit (probability

unit) dose/response relationship.

a. Action Area For listed species assessments, the action area is considered to be the area affected directly or indirectl y b y the Federal action and not merel y the immediate area where metrafenone is applied. At the initial L evel 1 screening assessment, broadly described taxonomic groups are considered, and thus, conservatively assumes that listed species within those broad groups are co
- located with the pesticide treatment area. This means that terrestrial plants and wildlife are assumed to be located on or adjacent to the treated site and aquatic organisms are assumed to be located in a surface water body adjacent t o the treated site. The assessment also assumes that listed species are located within the area of highest exposure to the pesticide, and that exposure will decrease with increasing distance from the treated area. If the assumptions associated with the screening
- level action area result in RQs that are below the listed species LOCs, a "no effect" determination conclusion is made with respect to listed species in that taxa, and no further refinement of the action area is necessary . Furthermore, RQs belo w the listed species LOCs for a given taxonomic group indicate no concern for indirect effects upon listed species that depend upon the taxonomic group covered by the RQ as a resource. However, in situations where the screening assumptions lead to RQs in excess of the listed species LOCs for a given taxonomic group, a potential for a "may affect" conclusion exists and may be associated with direct effects on listed species belonging to that taxonomic group or may extend to indirect effects upon listed spec ies that depend upon that taxonomic group as a resource. In such cases, additional information on the biology of listed species, the locations of these species, an d the locations of use sites could be considered along with available information on the fat e and transport properties of the pesticide to determine the extent to which screening assumptions regarding an action area appl y to a particular listed organism. These subsequent refinement steps could consider how this information would impact the actio n area for a particular listed organism and may potentiall y i nclude areas of exposure that are downwind and downstream of the pesticide use site.

b. Taxonomic Groups Potentially at Risk The preliminary

risk assessment for endangered species indicates that the proposed use and application rate for metrafenone either exceeds the Endangered Species LOCs for the following taxonomic groups (underlined [chronic exposure to mammals] ) or those for which risk cannot be precluded (also underlined [chronic exposure t o freshwater fish and invertebrates, acute exposure to marine/estuarine invertebrate, chronic exposure to marine/estuarine fish] )
.Page 90 of 114  Chronic exposure to mammals  Data was not submitted or was deemed invalid for the following: chronic exposure to freshwater invertebrates and marine/estuarine fish . A passerine bird study is also not available at this time. Lack of data does not preclude risk.  Data was supplemental, but inadequate for risk quotient ca lculations which would have helped to determine risk to endangered species for the following: acute exposure to freshwater fish and invertebrates, acute exposure to marine/estuarine invertebrates, chronic exposure to freshwater fish; and, aquatic plants. Therefore, there is uncertainty in determining risk to these taxonomic groups. However, the total concentration based endpoint (EC 50 : 0.22 mg total a.i./L) for the acute marine/estuarine invertebrate (eastern o ys ter) study (MRID 47267440) with an effect on shell deposition is 11x greater than the highest estimated E EC (0.02 mg/L), hence risk to federally listed marine/estuarine invertebrates cannot be precluded. The total concentration based endpoint (NOAEC: 0.118 mg total a.i./L) for the chronic freshwater fish (fathead minnow) study (MRID 47267449) with an effect o n post - hatch survival is approximately 7x greater than the highest estimated EEC (0.016 mg/L), hence risk to federally listed freshwater fish cannot be precluded. Applying similar calculations to the acute f reshwater fish and invertebrate data as well as d ata for aquatic plants assumes low risk to federally listed species.  Data was acceptable, but inadequate for risk quotient calculations for the following: acute exposure to marine/estuarine fish
. Therefore, there is uncertainty in determining risk to these taxonomic groups. The highest concentration tested in the acute marine/estuarine fish (sheepshead minnow) study (MRID 47267446) was 0.35 mg dissolved a.i./Lwhich is 17.5x greater than the highest estimated EEC (0.02 mg/L) but there were no effects on mor

tality or sublethal effects, hence risk to federall y listed marine/estuarine fish is assumed to be low. Acceptable data for acute exposure to birds yields non
- definitive endpoints with no effects; therefore, acute risk to federall y listed birds is expected to be low. For similar reasons, acute risk to federally listed piscivorous birds, mammals, and piscivorous mammals is also expected to be low.Page 91 of 114

Concerns For Federally Listed as Endangered and/or Threatened Species Table 35 . L isted Species Ris ks Associated w ith Direct or Indirect Effects from Metrafenone use on Grapes at the Maximum Proposed Application Rate (0.3 lbs a.i./A, Assuming 6 Applications/Year)

Listed Taxon Direct Effects Indirect Effects Terrestrial and semi
- aquatic plants
- mo nocots No Yes from effects to mammals Terrestrial and semi
- aquatic plants

– dicots No Yes from effects to mammals Ter restrial invertebrates No Yes from effects to mammals Birds No Yes from effects to mammals, FW fish, FW inverts, M/E fish, M/E invert s (mollusks) Terrestrial
- phase amphibians No Yes from effects to mammals Reptiles No Yes from effects to mammals, FW fi sh, FW inverts, M/E fish, M/E inverts (mollusks) Mammals Yes for chronic 1 Yes from effects to mammals, FW fish, FW inverts, M/E fish, M/E inverts (mollusks) Aquatic non
- vascular plants No Yes from effects to mammals, FW fish, FW inverts, M/E fish, M/E inverts (mollusks) Aquatic vascular plants No Yes from effects to mammals, FW fish, FW inverts, M/E fish, M/E inverts (mollusks) Freshwater (FW) fish Yes for chronic 2 Yes from effects to mammals, FW fish, FW inverts, M/E fish, M/E inverts (mollusks) Aquatic
- phase amphibians Yes for chronic 3 Yes from effects to mammals, FW fish, FW inverts, M/E fish, M/E inverts (mollusks) Freshwater (FW) invertebrates Yes for chronic 4 Yes from effects to mammals, FW fish, FW inverts, M/E fish, M/E inverts (mollus ks) Marine/estuarine (M/E) fish Yes for chronic 4 Yes from effects to mammals, FW fish, FW inverts, M/E fish, M/E inverts (mollusks) Marine/estuarine (M/E) invertebrates ( mo llusk) Yes for acute 5 , No for chronic 6 Yes from effects to mammals, FW fish, FW inverts, M/E fish, M/E inverts (mollusks) 1 The chronic LOC is exceeded on a dose basis for mammals in all size classes eating short grass, for the 15 and 35 gram size classes eating tall grass and broadleaf plants / small insects. The chronic LOC on a dietary basis is not exceeded for any of the food categories. 2 The total concentration based endpoint (NOAEC: 0.118 mg total a.i./L) for the chronic freshwater fish (fathead minnow) study (MRID 47267449) with an effect on post
- hatch survival is approximately 7x greater than the highest estimated EEC (0.016 mg/L), hence risk to federally listed freshwater fish cannot be precluded. 3 Results from freshwater fish used as surrogate for assessing risk to aquatic
- phase amphibians 4 Studies not submitted or inv alid for which risk cannot be precluded. 5 Mollusk (Eastern oyster); 6 Saltwater mysidPage 92 of 114 1. Discussion of risk quotients The Agency ’s LOCs for mammals (chronic) are exceeded for the use of metrafenone on grapes as outlined in previous sections. The risk to the remaining federall y listed taxonomic groups (freshwater fish and invertebrates (chronic), marine/estuarine invertebrate (acute), marine/estuarine fish (chronic)) cannot be precluded on the basis of toxicity data and estimated exposures. Should estim ated exposure levels occur in proximity to listed resources, the available screening level information suggests a potential concern for direct effects on listed species within the taxonomic groups listed above associated with the uses of metrafenone as des cribed in Section III. A. The registrant must provide information on the proximity of federall y listed mammals, freshwater fish and invertebrates, as well as marine/estuarine fis h and invertebrates to the metrafenone use sites. This requirement may be sati sfied in one of three ways: 1) having membership in the FIFRA Endangered Species Task Force (Pesticide Registration [PR] Notice 2000
- 2); 2) citing FIFRA Endangered Species Task Force data; or 3) independentl y producing these data, provided the information is of sufficient quality to meet FIFRA requirements. The information will be used b y the OPP Endangered Species Protection Program to develop recommendations to avoid adverse effects to listed species. 2. Probit dose response relationship The Agency

uses th e probit dose response relationship as a tool for providing additional information on the potential for acute direct effects to aquatic and terrestrial animals (U.S. EPA, 2004). As part of the risk characterization, an interpretation of acute RQ for liste d species is discussed. This interpretation is presented in terms of the chance of an individual event (i.e., mortality or immobilization) should exposure at the EEC actually occur for a species with sensitivity to metrafenone on par with the acute toxici ty endpoint selected for RQ calculation. To accomplish this interpretation, the Agency uses the slope of the dose response relationship available from the toxicity study used to establish the acute toxicity

measures of effect for each taxonomic group that is relevant to this assessment. The individual effects probability associated with the acute RQ is based on the mean estimate of the slope and an assumption of a probit dose response relationship. In addition to a single effects probability estimate bas ed on the mean, upper and lower estimates of the effects probability are also provided to account for variance in the slope, if available. The upper and lower bounds of the effects probability are based on available information on the 95% confidence inter val of the slope. Studies with good probit fit characteristics (i.e., statistically appropriate for the data set) are associated with a high degree of confidence. Conversel y, a low degree of confidence is associated with data from studies that do not statistically support a probit dose response relationship. In addition, confidence in the data set may be reduced by

high variance in the slope (i.e., large 95% confidence intervals), despite good probit fit characteristics. In the event that dose response information is not available to estimate a slope, a default slope assumption of 4.5 (95% C.I.: 2 to 9) (Urban and Cook, 1986) is used.Page 93 of 114

Individual effect probabilities are calculated based o n an Excel spreadsheet tool IEC v 1.1 (Individual Effect Chance M odel Version 1.1) developed by the U.S. EPA, OPP, Environmental Fate and Effects Division (June 22, 2004). The model allows for such calculations b y entering the mean slope estimate (and the 95% confidence bounds of that estimate) as the slope parameter f or the spreadsheet. In addition, the acute RQ is entered as the desired threshold. However, o n account of either non
- definitive acute endpoints or endpoints based on total concentrations (dissolved + undissolved test compound) instead of dissolved concentrations only , the acute studies which would otherwise be useful for calculating individual effect probabilities cannot be used. 3. Data related to under -represented taxa Effects data on under
- represented taxonomic groups were not submitted by the Registrant . Effects data from other anal yz ed sources were either not obtained (ECOTOX Database, PAN Database) or were not available (publicly available ECOTOX) for this screening risk assessment. 4. Implications of sublethal effects
For the sublethal effects discus sed below, it is noted that EFED cannot quantitatively assess the relationship between any of the observed sublethal effects and potential reduction in survival or reproductive impairment at this time. Instead, the concentrations at which sublethal effect s were observed in laboratory studies are discussed in relation to the concentrations at which mortality and/or reproductive effects were observed in the same laboratory

studies and compared to aquatic and terrestrial EECs and assessed as to whether or not they

may be expected under field conditions. The EU/UK formulation (BAS 560 00F), which is used in all formulation studies, closely matches the U.S. formulation ( i.e. , BAS 560 03F) but is not equivalent. The formulation studies are cited and evaluated in this assessment. However, at this time, the effect of the U.S. formulation on any given taxa is not known. Acute Studies Aquatic Organisms The greatest amount of uncertainty in the assessment stems from aquatic studies which were largel y based on total concentrations (both dissolved and undissolved) instead of the soluble concentrations of the test compound. Given the freshwater fish acute toxicity data the bluegill sunfish ( Lepomis macrochirus ) appears to be more sensitive than the rainbow trout ( Onc orhynchus mykiss ) on the technical grade active ingredient. Sublethal effects (lethargic and motionless fish) were observed in the bluegill study at the highest concentration tested (0.87 mg total a.i./L)Page 94 of 114

which is greater than the peak aquatic EEC (0.02 mg a.i./L) . Similarly , the lowest tested metabolite concentration at which sublethal effects were observed for the trout study was at 20.3 mg total a.i./L, which is also below the total metrafenone residue peak EEC. The numbers imply

that sublethal effects o n freshwater fish due to the parent or metabolite of metrafenone are not expected under field conditions. The freshwater invertebrate study on daphnia using the technical grade active ingredient and a metabolite (CL 375816) indicated no effects. On the o ther hand, another metabolite study (using CL 4084564) indicated immobility at 23.2 mg total a.i./L, which is also above peak EEC levels. The numbers imply that sublethal effects on freshwater invertebrates due to the parent or metabolite of metrafenone ar e not expected under field conditions. No effects were observed for the marine/estuarine fish technical grade active ingredient study . Erratic swimming was observed in the saltwater m ys id ( Americamysis bahia ) study at 0.416 mg total a.i./L and mortality at 0.129 mg total a.i./L, which are again above peak EEC levels. Therefore, the values imply that sublethal effects on marine/estuarine fish and invertebrates due to the parent metrafenone are not expected under field conditions. Terrestrial Organisms T he acute oral avian studies indicated no effects; the acute dietary avian studies indicated a significant change in body weight that was not associated with a dose
- response pattern. In the mammal study

on the technical grade active ingredient, only mortali ty was reported. Therefore, no implications with sublethal effects can be made. Chronic Studies Aquatic Organisms The freshwater fish chronic toxicity endpoint (NOAEC 0.118 mg total a.i./L) based on post - hatch is greater than the highest chronic EEC ( 0.017 mg a.i./L). Similarly , the marine/estuarine invertebrate chronic toxicity endpoint (NOAEC 0.022 mg a.i./L) based on reproduction is greater than the highest chronic EEC (0.018 mg a.i./L). The values imply that chronic effects on freshwater fish and m arine/estuarine invertebrates are not expected under field conditions. No acceptable chronic freshwater invertebrate studies are available. No chronic marine/estuarine fish studies were submitted for review. Terrestrial Organisms The avian chronic tox icity endpoint (NOAEC 848 mg a.i./kg diet) based on egg production and hatchability did not yield chronic LOC exceedances. The most sensitive chronic mammalian endpoint (NOAEL 35.9 mg/kg bw/day) based on decreased bodyPage 95 of 114

weights and body weight gain in F 1 males as well as body weights in F 1 and F 2 females, however, exceeded the chronic LOC , which implies that sublethal chronic effects on mammals are expected under field conditions.
c. Indirect Effects Analysis In conducting a screen for indirect effects, dire ct effects LOCs for each taxonomic group are used to make inferences concerning the potential for indirect effects upon listed species. The listed species rel y upon non - listed organisms in these taxonomic groups as resources critical to their life cycle. Pesticide
- use scenarios, resulting in RQs that are below all direct effect listed species LOCs for all taxonomic groups assessed are considered of no concern for risks to listed species either b y direct or indirect effects. However, there may

be situati ons where a taxonomic group is not quantitatively assessed (e.g., terrestrial insects), but other lines of evidence are sufficientl y supportive of concerns for indirect effects on listed organisms that are dependant upon that taxonomic group.

· Where One or More Animal Taxonomic Group RQs Exceed the LOC for Listed Species The Level I screening indirect effects anal ys is documents those ty pes of dependencies upon non - listed organisms that could be important sources of indirect effects to listed organisms sho uld effective levels of the pesticide coincide with locations of listed species and the biologically

based resources upon which they depend. In cases where screening
level acute RQs for a given animal group equal or exceed the endangered species acute LOC , the Agency

uses the dose response relationship from the toxicity study used for calculating the RQ to estimate the probability of acute effects associated with an exposure equivalent to the EEC. This information serves as a guide to establish the need f or and extent of additional anal ys is that may be performed using Services
- provided “species profiles” as well as evaluations of the geographical and temporal nature of the exposure to ascertain if a not likely to adversel y affect determination can be made. The degree to which additional anal ys es are performed is commensurate with the predicted probability

of adverse effects from the comparison of dose response information with the EECs. The greater the probability that exposures will produce effects on a taxa, the greater the concern for potential indirect effects for listed species dependant upon that taxa, and therefore, the more intensive the anal ys is on the potential listed species of concern, their locations relative to the use site, and information regarding the use scenario (e.g., timing, frequency , and geographical extent of pesticide application). The greatest concerns would exist when exposure is associated with a risk higher than the effects probability

associated with the non
- endangered LOC for a pesticide with an average slope of 4.5. For metrafenone, risks to listed species are predicted within the following taxa: mammals, freshwater fish and invertebrates, marine/estuarine invertebrates, and marine/estuarine fish
. Changes in fish and aquat ic invertebrate populations could indirectly affect other fish and aquatic invertebrates, aquatic plants, birds, reptiles andPage 96 of 114

mammals. The chronic endpoint for mammalian species is based on decreases in body weight and/or body weight gain in both the pare nts and pups. If body s ize following chronic metrafenone exposure is reduced to the extent that it has an impact on mammalian populations, reduction in mammalian populations that are used as a resource for listed species may

be of concern. Given that the chronic LOC is exceeded for mammals, indirect effects to listed species (e.g., other mammals, birds, amphibians, reptiles, plants (pollination) and terrestrial invertebrates) that rel y on mammals as a primary food source, or on mammal burrows for shelter or breeding habitat, may be of concern. d. Critical Habitat In the evaluation of pesticide effects on designated critical habitat, consideration is given to the phy sical and biological features (constituent elements) of a critical habitat identified by

the U.S Fish and Wildlife and National Marine Fisheries Services as essential to the conservation of a listed species and which may require special management considerations or protection. The evaluation of impacts for a screening level pesticide risk asses sment focuses on the biological features that are constituent elements and is accomplished using the screening
- level taxonomic analy sis (risk quotients, RQs) and listed species levels of concern (LOCs) that are used to evaluate direct and indirect effects to listed organisms. The screening
- level risk assessment has identified potential concerns for indirect effects on listed species for those organisms dependant upon mammals, freshwater fish and invertebrates, marine/estuarine invertebrates, and marine/est uarine fish
. In light of the potential for indirect effects, the next step for EPA and the Service(s) is to identify which listed species and critical habitat are potentiall y i mplicated. Anal yt icall y, the identification of such species and critical habitat can occur in either of two way s. First, the agencies could determine whether the action area overlaps critical habitat or the occupied range of an y listed species. If so, EPA would examine whether the pesticide's potential impacts on non
- endangered spe cies would affect the listed species indirectly or directly affect a constituent element of the critical habitat. Alternativel y, the agencies could determine which listed species depend on biological resources, or have constituent elements, that fall into the taxa that may be directly

or indirectl y impacted by the pesticide. Then EPA would determine whether use of the pesticide overlaps the critical habitat or the occupied range of those listed species. At present, the information reviewed b y EPA does no t permit use of either analy tical approach to make a definitive identification of species that are potentiall y impacted indirectl y or critical habitat that is potentially

impacted directl y b y the use of the pesticide. EPA and the Service(s) are working tog ether to conduct the necessary anal ys is. This screening
- level risk assessment for critical habitat provides a listing of potential biological features that, if they are constituent elements of one or more critical habitats, would be of potential concern. These correspond to the taxonomic groups identified above as being of potential concern for indirect effects (i.e., mammals, freshwater fish and invertebrates, marine/estuarine invertebrates, and marine/estuarine fish ). This shouldPage 97 of 114

serve as an initial st ep in problem formulation for further assessment of critical habitat impacts outlined above, should additional work be necessary
.

e. Co - occurrence Analysis The goal of the anal ys is for co
- location is to determine whether sites of pesticide use are geograph ically

associated with known locations of listed species. At the screening level, this analy sis is accomplished using the LOCATES v. 2.10. 4 database. The database uses location information for listed species at the county level and compares it to agricultural census data for crop production at the same county level of resolution. The product is a listing of federall y listed species that are located within counties known to produce the crop upon which the pesticide will be used. Tables 3 6 and 3 7 below report the number of states and counties in which endangered species reside that have the proposed metrafenone use
. The ‘grape’ category was selected in L OCATES
. The data suggest that there is considerable potential for exposure to a variety of endangered species from metrafenone use. For additional L OCATES output refer to Appendix E
.



## Species Counts by State for Indicated Crops

No species were excluded. Minimum of 1 Acre. All Medium T yp es Reported 

### grapes AL, AK, AZ, AR, CA, CO, CT, DE, DC, FL, GA, HI, ID, IL, IN, IA, KS, KY, LA, ME, MD, MA, MI, MN, MS, MO, MT, NE, NV, NH, NJ, NM, NY, NC, ND, OH, OK, OR, PA, PR, RI, SC, SD, TN, TX, UT, VT, VA, WA , W V, WI , W Y Table 3 6 . Number of Endangered Species Potentially Exposed to Metrafenone with the Proposed Us es

Mam mals Am phibians Birds Reptiles Arachnids Insects Conf/Cyc Dicot Ferns Lichen Monocots Counties 744 93 595 231 12 153 6 493 28 14 272 States 47 11 43 24 4 28 3 41 8 4 37 Species 129 21 163 74 13 73 4 607 20 4 109 Table 3 7 . Number of Endangered Species Potentially Exposed to

Metrafenone with the Proposed Uses Bivalve Crustacean Fish Gastropod Marine Mamm al Counties 290 56 449 44 50 States 27 13 38 16 7 Species 205 21 197 32 10Page 98 of 114

C. Description of Assumptions, Limitations, Uncertainties, Stren gths, and Data Gaps 1. Assumptions, Limitations, and Uncertainties Related to

Exposure for all Taxa
a. Maximum Use Scenario The screening
- level risk assessment focuses on characterizing potential ecological risks resulting from a maximum use scenario, which is determined from labeled statements of maximum application rate and number of applications with the shortest time interval between applications. The frequency at which actual uses approach this maximum use scenario may

be dependant on fungicide resistanc e, timing of applications, cultural practices, and market forces. 2. Assumptions, Limitations, and Uncertainties Related to Exposure for Aquatic Species
a. Environmental Fate Studies All of the environmental fate studies for the parent compound were de termi ned to be scientifically valid and therefore results from all of the studies can be used to characterize the mobility

and rates of transformation of metrafenone. However, many of the metabolism studies have major uncertainties in the identification and pattern of formation and decline of transformation products. In all of the aquatic metabolism studies, between 57% and 65% of the applied radioactivity remains unidentified with incomplete characterization, and in two aerobic soil metabolism studies, 15% an d 44% of the applied radioactivity

is unidentified. This includes at least four major degradates that individually

reach levels of 11% to 35% of the applied. Other transformation products appear as groups of up to 15 components, in some cases characteriz ed as each being <5% of the applied radioactivity , but in other cases, some individual components make up 9% to 10% of the applied. Even when individual components can all be classified as minor degradates, these groups represent such a large portion of the applied radioactivity overall that the possibility

that they may have some impact as a group cannot be precluded despite their lower individual levels. This is especially true given that the degradation pathway s suggest that groups of degradates may have a high degree of structural similarity and so may

have similar fate and effects behavior. Without information to adequatel y characterize the degradates, it may be necessary

to assume that they

are of equal toxicity

to the parents in order to quantify risks. b. Aquatic Exposure Modeling The lack of complete characterization and identification of degradation products prompted additional aquatic exposure modeling on total metrafenone residues. Although this modeling approach is conservative, it is reasonab le modeling approach to address uncertainties in degradation product identification.Page 99 of 114 c. Bioaccumulation Modeling Bioaccumulation modeling was conducted because metrafenone has a log Kow > 4. The bioaccumulation modeling was conducted using guidance for the KABAM model. It is recommended to report the sediment pore water and water column concentrations at the appropriate time when the pesticide concentration reaches steady- state. An evaluation of the time series for metrafenone showed no clear plateau in me trafenone concentrations. Therefore, the appropriate averaging time was selected at 21 days to serve as a conservative exposure concentration for bioaccumulation modeling.
3. Assumptions, Limitations, and Uncertainties Related to Exposure for Terrestrial Species
a. Location of Wildlife Species For this screening
- level terrestrial risk assessment, a generic bird or mammal was assumed to occup y either the treated field or adjacent areas receiving metrafenone at the treatment rate on the field. Actual habitat requirements of any particular terrestrial species were not considered, and it was assumed that species occup y, exclusively and permanentl y, the modeled treatment area. Spray drift model predictions suggest that this assumption leads to an overestimatio n of exposure to species that do not occup y the treated field exclusively

and permanently
. b. Routes of Exposure This screening
- level assessment for ground (liquid) applications of metrafenone only considered dietary

exposure. Other routes of exposure that were not considered in the assessment are incidental soil ingestion exposure, inhalation exposure, dermal exposure, and drinking water exposure.
c. Dietary Intake and Other Limitations of Oral Studies in Terrestrial Species The avian acute oral study and th e avian subacute dietary study each have limitations for estimating the risk to wild species exposed to pesticides in the environment. Both studies have a fixed exposure period and do not allow for differences in the responses of individuals to different durations of exposure. With the acute oral study , the chemical is administered in a single dose. This does not mimic wild bird exposure through multiple feedings. Also, it does not account for the effect of different environmental matrices on absorption rate into the gastrointestinal tract of the animal. With the acute dietary study , the endpoint is reported as the concentration mixed with food that produces a response rather than as the dose ingested. Although food consumption sometimes allows for est imation of a dose, calculations of the mg/kg/day are confounded by

undocumented spillage of feed and how consumption is measured over the duration of the test. Usually , if measured at all, food consumption is estimated once at the end of the five
- day expo surePage 100 of 114

period. Group housing of birds undergoing testing allows for a measure of only the average consumption per day for a group, and consumption estimates can be further confounded if birds die within a treatment group. In addition, the dietary study uti lizes yo ung birds. The exponential growth of young birds complicates the estimate of the dose; controls often nearly double in size over the duration of the test. Since weights are only taken at the initiation and at the end of the exposure period, the dose per body weight (mg/kg) is difficult to estimate with any precision. The interpretation of this test can be further confounded by dietary consumption. Estimation of the acute L C 50 value is not only a function of the intrinsic toxicity of the pesticid e, but also the willingness of the birds to consume treated food. In addition to the uncertainties associated with the two toxicity studies utilized for estimating acute risk to birds, other factors, not normally taken into account in a screening level risk assessment may narrow the differences between the dose
- based and dietary
- based acute RQs for birds. The factors include differences in gross energy and assimilative efficiency

of laboratory

feed versus food items in the field, basic maintenance metabo lic rates between wild birds and captive birds, seasonal free living dietary requirements for wild birds (including gorging behavior) and specific food avoidance behavior. These uncertainties may either overestimate or underestimate the risk in a screenin g level assessment. Gross Energy and Assimilative Efficiency . This screening level risk assessment does not allow for gross energy and assimilative efficiency differences between wildlife food items and laboratory

feed. For example, a typical laboratory avian feed, as used, contains approximately

2750 kcal/ kg. The Agency ’s Wildlife Exposure Factors Handbook (U.S. Environmental Protection Agency , 1993) presents the following dry
- weight and fresh weight caloric contents for selected wildlife food items:

Food Item Energy Dry (kcal/kg) Energy Fresh (kcal/kg ) grasses 4200 1300 broadleaf forage 4200 2200 seeds 5100 4700 fruits 2000 1100 insects 5600 1600 On gross energy

content alone, direct comparison of a laboratory dietary co ncentration
based effects threshold to a fresh
- weight pesticide residue estimate would result in an underestimation of field exposure by food consumption by

a factor of 1.25
- 2.5 for most food items. Only

for seeds would the direct comparison of dietary threshold to residue estimate lead to an overestimate of exposure. Depending upon species and dietary matrix, bird assimilation of wild diet energy ranges from 23
- 80%, and mammal’s assimilation ranges from 41
- 85% (U.S. EPA , 1993). If it is assumed th at laboratory chow is formulated to maximize assimilative efficiency (e.g., a value of 85%), a potential for underestimation of exposure may exist by assuming thatPage 101 of 114

consumption of food in the wild is comparable with consumption during laboratory testing. M etabolic Rates. In the screening process, exposure may be underestimated because metabolic rates are not related to food consumption. For example, the Wildlife Exposure Factors Handbook (U.S. EPA , 1993) includes allometric models for estimating both exi sting metabolic rate (EMR) and free living metabolic rate (FMR). EMR is the metabolic rate necessary

for animal maintenance in captivity without body

weight loss, a condition similar to caged test animals. FMR is the energy requirement for an organism in the wild. For passerine birds these relationships are as follows: EMR (kcal/day) = 1.572 (body weight g) 0.6210 FMR (kcal/day) = 2.123 (body weight g) 0.749 Using a weight range for passerines of 10
- 150 g, the EMR predictions range from 6.6 to 35.3, and the FMR ranges from 11.9 to 90.5 kcal/day . Thus, it appears that not accounting for increased energy demands of organisms in the wild when comparing dietary residues to dietary

toxicity thresholds represents about a two
- fold underestimation in exposur e potential. Free Living Metabolic Requirements. The screening procedure does not account for situations where the feeding rate may be above or below requirements to meet free living metabolic requirements. Gorging behavior is a possibility under some s pecific wildlife scenarios (e.g., bird migration) where the food intake rate may be greatl y i ncreased. Kirkwood (1983) has suggested that an upper
- bound limit to this behavior might be the ty pical intake rate multiplied by a factor of 5. Avoidance. In contrast is the potential for avoidance, operationally defined as animals responding to the presence of noxious chemicals in their food b y reducing consumption of treated dietary

elements. This response is seen in nature where herbivores avoid plant seco ndary compounds. For agrochemicals, Dolbeer et al. (1994) reported that the use of methiocarb on fruit crops reduced depredation by birds. Of course, chemical treatment of food sources and an y subsequent avoidance of those food sources b y a species may, in itself, result in detrimental effects on the energetics of the species. d. Incidental Releases Associated with Use This risk assessment was based on the assumption that the entire treatment area is subject to pesticide application at the rates specified on the label. Uneven application of the pesticide through changes in calibration of application equipment, spillage, and localized releases at specific areas of the treated field that are associated with specifics of the ty pe of application equipment were not accounted for in this assessment.Page 102 of 114 e. Residue Levels Selection The Agency

relies on the work of Fletcher et al. (1994) for setting the assumed pesticide residues in wildlife dietary items. These residue assumptions are believed to reflect a realistic upper - bound residue estimate, although the degree to which this assumption reflects a specific percentile estimate is difficult to quantify . It is important to note that the field measurement efforts used to develop the Fletcher estimates of exposure inv olve highl y varied sampling techniques. It is entirel y possible that much of these data reflects residues averaged over the entire above ground plants in the case of grass and forage sampling. Depending upon a specific wildlife species’ foraging habits, whole aboveground plant samples may either underestimate or overestimate actual exposure. f. TerrPlant Model At this time, the TerrPlant model cannot accurately estimate terrestrial exposure levels with pesticides applied with multiple applications or appli cation intervals. The technology

is not yet available for these types of estimations. The label states that a maximum of 1.8 lbs a.i./A may be applied per season, with a maximum of six applications the highest single application rate is 0.3 lbs a.i./A. Inmodeling the terrestrial EECs, it was assumed that there was one application per ye ar. If assuming one application of 1.8 lbs a.i./A the RQ values may be considered an overestimate of risk, but assuming one application of 0.3 lbs a.i./A the RQ values may be considered an underestimate of risk. Therefore, the model was used to bracket the potential risk on terrestrial plants as a result of metrafenone use.
4. Assumptions, Limitations, and Uncertainties Related to Effects Assessment
a. Sublethal Effects For an acute risk assessment, the screening risk assessment relies on the acute mortality endpoint as well as a suite of sublethal responses to the pesticide, as determined by the testing of species response to chronic exposure conditions and subsequent chroni c risk assessment. Consideration of additional sublethal data in the assessment is exercised on a case - by
- case basis and only after careful consideration of the nature of the sublethal effect measured and the extent and quality of available data to support establishing a plausible relationship between the measure of effect (sublethal endpoint) and the assessment endpoints. b. Age Class and Sensitivity of Effects Thresholds Testing of juvenile organisms may overestimate toxicity

at older age classes for pest icidal active ingredients that act directly (without metabolic transformation) because younger age classes may

not have the enzy

matic s ys tems associated with detoxifying xenobiotics. However, the influence of age may not be uniform for all compounds, and c ompoundsPage 103 of 114

requiring metabolic activation may be more toxic in older age classes. The risk assessment uses the most sensitive life
- stage information as the conservative screening endpoint.
c. Use of Most Sensitive Species Tested Screening risk assessment re lies on a selected toxicity endpoint from the most sensitive species tested; however, the selected toxicity endpoints do not necessaril y reflect sensitivity

of the most sensitive species in a given environment. The relative position of the most sensitive s pecies tested in the distribution of all possible species is a function of the overall variability

among species to a particular chemical. Toxicity thresholds may vary up to four orders of magnitude across species for some chemicals 11 . Therefore, risk conc lusions may

under
- or overestimate actual ecological risk for a given species.
5. Assumptions, Limitations, Uncertainties, Strengths, and Data Gaps Related to the Acute and Chronic LOC’s The risk characterization section of the assessment document include s an evaluation of the potential for individual effects to listed species at an exposure level equivalent to the LOC. This evaluation is based on the median lethal dose estimate and dose/response relationship established for the effects study correspondin g to each taxonomic group for which the LOCs are exceeded. The slope of the probit
- dose response is used to generate a probability

of individual effects near the low end tail of the curve. Predictions based on low probability

events are by

nature highl y uncertain. Moreover, for this assessment the dose
- response curve representing a given taxa is generated from one study using one species. It is likely

that the resulting dose
- response relationship does not represent the response of all species within a t axa. Calculating the probability of individual effects at the lower and upper bounds of the slope is designed to address this source of uncertainty but the extent to which this captures the variability within a taxa is unknown. In some cases, a probit do se - response relationship cannot be calculated. In these instances, event probabilities are calculated based on a default slope assumption of 4.5 (Urban and Cook, 1986).

11 Mayer, F.L. and M.R. Ellersieck, 1986. Manual of acute toxicity: Interpretation and data

base for 410 chemicals of freshwater animals. Resource Publication 160. U. S. Fish and Wildlife Service. Department of the Interior, Washington, D.C., 579 p.Page 104 of 114

V. Literature Cited Open L iterature and Other Documents Arnot, J.A. and F.A. P.C. Gobas. 2004. A food web bioaccumulation model for organic chemicals in aquatic ecosystems. Environmental Toxicology and Chemistry, v23 (10), 2343
- 2355

. Draft Assessment Report (DAR). 2005. Initial risk assessment provided b y the rapporteur Member State United Kingdom for the new active substance: Metrafenone as referred to in Article 8(1) of Council Directive 91/414/EEC. July 2005. Fletcher, J.S., J.E. Nellesson, and T. G. Pfleeger. 1994. L iterature review and evaluation of the EPA food
- chain (Kenag a) nomogram, an instrument for estimating pesticide residues on plants. Environ. Tox. and Chem. 13(9):1383
- 1391. Hoerger, F. and E.E. Kenaga. 1972. P esticide residues on plants: correlation of representative data as a basis for estimation of their magni tude in the environment. IN: F. Coulston and F. Corte, eds., Environmental Quality and Safety : Chemistry , Toxicology and Technology
. Vol 1. G eorge Theime Publishers, Stuttgart, Germany . pp. 9
- 28. Opalski, K., Tresch, S., Kogel, K
- H, Grossmann, K., Kohl e, H. and R. Huckelhoven. 2006. Metrafenone: Studies on the mode of action of a novel cereal powdery mildew fungicide. Pest Management Science , 62(5), p.393
- 401. ISSN 1526
- 498X. Urban, D.J. and N.J. Cook, 1986. Hazard Evaluation Division Standard Evaluation Procedure Ecological Risk Assessment. EPA 540/9
- 85
- 001. U.S. Environmental Protection Agency , Office of Pesticide Programs, Washington D.C. U.S. Environmental Protection Agency (USEPA). 1993. Wildlife Exposure Factors Handbook. Office of Research and Development, Washington, D.C. EPA/600/R
13/187a. U.S. Environmental Protection Agency (USEPA) 1998 . Guidelines for Ecological Risk Assessment. EPA/630/R
- 95/002F. Published in 63 FR 26846; May 14, 1998. U.S. Environmental Protection Agency , Washin gt on, DC. April, 1998. U.S. Environmental Protection Agency (USEPA). 2004. Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs, U.S. Environmental Protection Agency . Endangered and Threatened Species Effects Determinations. Office of Prevention, Pesticides and Toxic Substances, Office of Pesticide Programs, Washington, D.C. January 23, 2004. Online at: http://www.epa.gov/oppfead1/e ndanger/consultation/ecorisk
- overview.pdfPage 105 of 114

U.S. Environmental Protection Agency (USEPA). 2006. Pesticide Fact Sheet: Metrafenone. New Chemical. September 2006. U.S. Environmental Protection Agency (USEPA). 2008. (Terrestrial Residue EXposure model) Vers ion 1.4.1 (10/09/08). Environmental Fate And Effects Division, Office Of Pesticide Programs, U.S. Environmental Protection Agency
. Willis, G.H., and L .L . McDowell. 1987. Pesticide Persistence on Foliage in Reviews of Environmental Contamination and Tox icology . 100: 23
- 73. Fate Studies Submitted to the USEPA/Office of Pesticide Programs MRID 47267450 Zulalian, J. 2001. BAS 560 F (AC 375839): uptake, depuration, bioconcentration and metabolism of carbon
- 14 labeled AC 375839 in bluegill sunfish ( Lepo mis macrochirus ) under flow
- through conditions: Unpublished study performed by

BASF Corporation, BASF Agro Research, Princeton, NJ (Analy tical Phase) and ABC Laboratories, Inc., Aquatic Toxicology

Programs Division, Columbia, MO (In
- Life Phase; p. 39; Appe ndix B, pp.221
- 346). MRID 47267436 Xing, J. 2002. BAS 560 F (CL 375839): laboratory validation of L C/MS determinative and L C/MS/MS confirmatory method M 3503 for the determination of BAS 560 F and CL375816 residues in drinking and surface water. Unpub lished study performed by BASF Agro Research, Princeton, New Jersey
. MRID 47267435 Travis, D. 2002. BAS 560 F (CL 375839): laboratory validation of LC/MS determinative and LC/MS/MS confirmatory method M 3441 for the determination of BAS 560 F and CL377 160 residues in soil. Unpublished study performed by

BASF Agro Research, Princeton, New Jersey ; sponsored and submitted by BASF Corporation, Research Triangle Park, North Carolina. MRID 47267434 Smalley , R. 2001. Method validation of RLA 12618.00 "LC
- MS determination of CL 375839 and CL377160 residues in soil". Unpublished study performed by

BASF Agro Research, Gosport, Hampshire, United Kingdom. MRID 47267431 Panek, M, et al . 2008 . Anaerobic aquatic metabolism of 14C
- BAS 560 F. Unpublished study performed, sponsored and submitted by BASF Corporation, Research Triangle Park, North Carolina.Page 106 of 114

MRID 47267430 Yan, Z. and R.A. Huang. 2002 . BAS 560 F (AC 375839): aerobic transformation in water - sediment sy stems (including Amendment #1). Unpublishe d study performed by BASF Corporation, Ewing, New Jersey
. MRID 47267429 Huang, R. 2002 . BAS 560 F: anaerobic soil metabolism. Unpublished study performed, sponsored and submitted by BASF Corporation, Research Triangle Park, North Carolina.
MRID 4726 728 Afzal, J. 2002. CL377160 (metabolite of BAS 560 F) rate of degradation in three different soils under aerobic conditions. Unpublished study performed by

BASF Corporation, Princeton, New Jersey
. MRID 47267427 Singh, M. 2008. Aerobic soil metabolism of 14 C
- BAS 560 F on US soils. Unpublished study performed, sponsored and submitted by BASF Corporation, Research Triangle Park, North Carolina. MRID 47267426 Steinführer, T. 2000. 14 C
- AC 375839 (CL375839) Rate of degradation in three different soils under aerobic conditions. Unpublished study performed b y C yanamid Forschung GmbH, Schwabenheim, German y. MRID 47267425 Steinführer, T. 2000. AC 37589: Metabolism in soil under aerobic conditions. Unpublished study

performed by

C yan amid Forschung GmbH , Schwabenheim, German y. MRID 47267424 Ta, C. 2001. BAS 560 F (AC 375839): Soil photoly sis. Unpublished study performed b y BASF Agro Research, Ewing, New Jersey
. MRID 47267423 Fung, C.H. 2002. BAS 560 F (AC 375839): Aqueous photoly sis. Unpublishe d study conducted b y BASF Agro Research, Princeton and Ewing, New Jersey
. MRID 47267422 An, D. 1999. AC 375839: Hydrol ys is. Unpublished study performed by

American Cyanamid Compan y, Ewing, New Jersey
. MRID 47267421 Tornisielo, A. and R. Hoefs. 2008. Adsorption/desorption of a metabolite of BAS 560 F (Reg. No. 4082230) on US soils (including Amendment No. 1). Unpublished studyPage 107 of 114

performed b y BASF SA, Guaratingueta, Brazil; and sponsored and submitted by BASF Corporation, Research Triangle Park, North Carolina. MRID 47267421 Tornisielo, A. and R. Hoefs. 2008. Adsorption/desorption of BAS 560 F on US soils (including Amendment No. 1). Unpublished study performed by

BASF SA, Guaratingueta, Brazil; and sponsored and submitted by BASF Corporation, Rese arch Triangle Park, North Carolina MRID 47267432 Jordan,J. J.M. Stewart, and R. Warren. 2008. Terrestrial field dissipation of BAS 560 00F in vineyard/orchard and row crop use patterns. Unpublished study performed by

Research for Hire, Porterville, CA (fi eld phase), Quails Agricultural Laboratory , Inc. Canada (field phase), Vaughn Agricultural Research Services, Branchton, Ontario (field phase), Research Options, Inc., Winter Garden, Florida (field phase), BASF RTP, NC (anal yt ical phase); and Agvise Laboratories, Inc. Northwood ND.
Effects Studies Submitted to the USEPA/Office of Pesticide Programs MRID 47267502 Ahmed, M.S., R. Troup and T. Harris. 2000(a). Avian acute oral toxicity test with AC 375839 Technical in Northern Bobwhite ( Colinus virginianus )
. BASF Doc ID 2000/7000117. MRID 47267503 Ahmed, M.S., R. Troup and T. Harris. 2000(b). Avian acute oral toxicity test with AC 375839 Technical in Mallard Duck ( Anas platyrhynchos ). BASF Doc ID 2000/7000115. MRID 47267504 Ahmed, M.S., R. Troup and T. Har ris. 2000(c). Avian dietary toxicity test with AC 375839 Technical in Northern Bobwhite ( Colinus virginianus ). BASF Doc ID 2000/7000126. MRID 47267505 Ahmed, M.S., R. Troup and T. Harris. 2000(d). Avian dietary toxicity test with AC 375839 Technical in Mallard Duck ( Anas platyrhynchos ). BASF Doc ID 2000/7000125. MRID 47267506 Ahmed, M.S. and M. Rodgers. 2002. BASF: Assessment to determine the effects on reproduction in Northern Bobwhite ( Colinus virginianus ). BASF Doc ID 2002 /7005090. MRID 47267515 Barke r, C., K.Drottar and H. Krueger. 2000(a). Effect of AC 375839 on growth of the green alga, Selenastrum capricornutum . BASF Doc ID 2000/7000122.Page 108 of 114

MRID 47267449 Barker, C., K.Drottar and H. Krueger. 2000(b). Toxicity of AC 375839 during the earl y life
- stages of the Fathead Minnow ( Pimephales promelas ). BASF Doc ID 2000/7000128. MRID 47267447 Barker, C., K.Drottar and H. Krueger. 2000(c). Toxicity of AC 375839 during the life
cycle of the Cladoceran (

Daphnia magna ). BASF Doc ID 2000/7000130. MRID 47267448 Caf arella, M. 2007. BAS 560 F

– Life
- cycle toxicity test with my sids (

Americamysis bahia ). BASF Doc ID 2007 /7009454. MRID 47267 512 Desjardins, D. Kendall, T., Krueger, H. and A. Van Cott. 2005(a). A 96
- hour toxicity test with the freshwater alga ( Anabaena flos - aquae ). BASF Doc ID 2005/7003441. MRID 47267514 Desjardins, D. Kendall, T., Krueger, H. and A. Van Cott. 2005(b). A 96
- hour toxicity test with the freshwater diatom ( Navicula pelliculosa ). BASF Doc ID 2005/7003436. MRID 47267513 Desjardins, D. Kendall , T., Krueger, H. and A. Van Cott. 2005(c). A 96
- hour toxici ty test with the marine diatom ( Skeletonema costatum ). BASF Doc ID 2005/ 7003443
. MRID 47267511 Desjardins, D. Kendall, T., Krueger, H. and A. Van Cott. 2005(d). A 7
- day static renewal toxicity te st with duckweed (

Lemna gibba G3 ). BASF Doc ID 2005/ 7003440
. MRID 47267438 Jatzek, J. 2002(a). CL375816 (Metabolite of BAS 560 F, Benzophenone)

– Determination of the acute effect on the swimming ability of the water flea Daphnia magna STRAUS. BASF Doc I D 2002/1004870. MRID 47267516 Jatzek, J. 2002(b). CL375816 (Metabolite of BAS 560 F, Benzophenone)

– Determination of the inhibitory effect on the cell multiplication of unicellular green algae. BASF Doc ID 2002/1004873. MRID 47267439 Jatzek, J. 2002(c ). CL4084564 (Metabolite of BAS 560 F, Benzophenone)

– Determination of the acute effect on the swimming ability of the water flea Daphnia magna STRAUS. BASF Doc ID 2002/1004869. MRID 47267517 Jatzek, J. 2002(d). CL4084564 (Metabolite of BAS 560 F, Benz ophenone)

– Determination of the inhibitory effect on the cell multiplication of unicellular green algae. BASF Doc ID 2002/1004872.Page 109 of 114

MRID 47267501 Krueger, H., MacGregor, J., Jaber, M. and C. Barker. 2001. Toxicity of BAS 560 F to Chironomus riparius durin g a prolonged sediment toxicity test. BASF Doc ID 2001/7000462. MRID 47267519 Luhrs, U. 2001. Acute toxicity (14 day s) of Metabolite CL377160 (Metabolite of BAS 560 F, Benzophenone) to the earthworm Eisenia fetida in artificial soil. BASF Doc ID 2001/ 1 007447. MRID 47267518 Mulligan, E. 2001(a). Acute toxicity of AC 375839 to the earthworm Eisenia fetida
. BASF Doc ID 2001/7000259. MRID 47267608 Mulligan, E. 2001(b). Acute toxicity of AC 375839 300 g/L SC RLF 12359 (SF 10358) to the earthworm Eisenia fe tida . BASF Doc ID 2001/7000262. MRID 47267442 Palmer, S. Krueger, H. MacGregor, J. and G Mitchell. 1999(a). Acute toxicity of AC 375839 to bluegill, Lepomis macrochirus , under flow
- through test conditions. BASF Doc ID 1999/7000286. MRID 47267443 Palmer, S. Krueger, H. MacGregor, J. and G Mitchell. 1999(b). Acute toxicity of AC 375839 to rainbow trout, Oncorhynchus mykiss , under flow
- through test conditions. BASF Doc ID 1999/7000289. MRID 47267437 Palmer, S. Krueger, H. MacGregor, J. and G Mitchell. 1999( c). Acute toxicity of AC 375839 to Daphnia magna under static test conditions. BASF Doc ID 1999/7000287. MRID 47267605 Palmer, S. Krueger, H. MacGregor, J. and C. Barker. 2001(a). Acute toxicity of BAS 560 00F (SF 10358, RLF 12359) to rainbow trout ( Oncorhynchus mykiss ) under static test conditions. BASF Doc ID 2001/7000463. MRID 47267604 Palmer, S. Krueger, H. MacGregor, J. and C. Barker. 2001(b). Acute toxicity of BAS 560 00F (SF 10358, RLF 12359) to Daphnia magna under static test conditions. BASF Doc ID 2001/7000464.Page 110 of 114

MRID 47267607 Palmer, S. Krueger, H. MacGregor, J. and C. Barker. 2001(c). Acute toxicity of BAS 560 00F (SF 10358, RLF 12359) on growth of the green alga, Selenastrum capricornutum
. BASF Doc ID 2001/7000465. MRID 47267441 Palmer, S. , T. Kendall, H. Krueger and A. Van Cott, 2005(a). A 96
- hour flow
- through acute toxicity

test with the saltwater m ys id ( Americamysis bahia ). BASF Doc ID 2005/7003438. MRID 47267446 Palmer, S., T. Kendall, H. Krueger and A. Van Cott, 2005(b). A 96
- hour flo w - through acute toxicity

test with the sheepshead minnow ( Cyprinodon variegatus ). BASF Doc ID 2005/7003439. MRID 47267 440 Palmer, S., T. Kendall, H. Krueger and A. Van Cott, 2005(c ). A 96
- hour shell deposition test with the eastern o ys ter ( Crassostrea vir ginica ). BASF Doc ID 2005/7003442
. MRID 47267510 Porch, J. and H. Krueger. 2001. Effect of BAS 560 F 500g/L SC (RLF 12380) on vegetative vigor of ten species of plants. BASF Doc ID 2001/7002392. MRID 47267509 Porch, J., K. Martin, and H. Krueger. 2001. E ffect of BAS 560 F 500 g/LSC (RLF 12380) on seedling emergence of ten species of plants. BASF Doc ID 2001/7002391. MRID 47267508 Strnad, A. and E. Mulligan. 2002(a). Acute toxicity of AC 375839 Technical to the honey bee, Apis mellifera . BASF Doc ID 2002/ 7004414. MRID 47267606 Strnad, A. and E. Mulligan. 2002(b). Acute toxicity of AC 375839 in a 300 g/L SC (SF 10358/RLF 12359) to the honey bee, Apis mellifera . BASF Doc ID 2002/7004415. MRID 47267444 Zok, S. 2002(a). Reg. No. 4074484 (Metabolite of BAS 560 F)

– Acute toxicity study on the rainbow trout ( Oncorhynchus mykiss ) in a static sy stem over 96 hours. BASF Doc ID 2002/1004394. MRID 47267445 Zok, S. 2002(b). CL 4084564 (Metabolite of BAS 560 F)

– Acute toxicity study on the rainbow trout ( Oncorhynchus mykiss ) in a static sy stem over 96 hours. BASF Doc ID 2002/1005255.Page 111 of 114

MRID 47267507 Zok, S. 2006. BAS 560 F

– 1 Generation reproduction study on the mallard duck (

Anas platyrhynchos ) b y administration in the diet. BASF Doc ID 2006/1018046.Page 112 of 114

VI. Appendices Appendix A. Chemical Names, Structures, and Maximum Reported Amounts of Metrafenone and Its Degradates. Appendix B. Aquatic Model Input/Output Data. Appendix C. Ex ample T
- REX Output for Metrafenone. Appendix D. E xample KABAM (v. 1.0) Results for Metrafenone. Appendix E. LOCATES Output of L isted Species. Appendix F. Submitted Environmental Fate Studies for Metrafenone. Appendix G. Submitted Ecological Effects Studies for Metrafenone. Appendix H. The Risk Quotie nt Method.

VII. List of Figures Figure 1. Chemical Structure of Metrafenone...................................................13 Figure 2. Conceptual Model Depicting Sources of Exposure from Metrafenone as well as Metrafenone Residues , Potential Receptors, and Adverse Effects from the Proposed Uses of Metrafenone on Grapes.........................................................................19
VIII. List of Tables Table 1. Summary

of Environmental Risk Conclusions for Aquatic Animals and Plants from Metrafenone Use on Grapes at the Maximum Proposed Application Rate.............6 Table 2. Summary

of Environmental Risk Conclusions for Terrestrial Animals and Plants from Metrafenone Use on Grapes at the Maximum Proposed Application Rate.............6 Table 3. Listed Species Risks Associated with Direct or Indirect Effects from Metrafenone use on Gra

pes at the Maximum Proposed Application Rate...................12 Table 4. Environmental Fate Properties of Metrafenone.......................................14 Table 5. Metrafenone Use and Application Information Based on the Proposed Label for Metrafenone 300 SC...................................................................... ..........15Page 113 of 114

Table 6. Test Species Evaluated for Assessing Potential Ecological Effects of Metrafenone and the Associated Acute Toxicity Classification...............................16 Table 7. Measures of Ecological Effects and Exposure for Metrafenone ...................26 Table 8. Total Extractable Metrafenone Residue Half
- lives from Laboratory

Degradation Studies....................................................................................... .........32 Table 9. Scenarios used to Estimate Metrafenone Concentrations in Surface Water.......33 Table 10. PRZM/EXAMS Input Parameteres for Metrafenon e and Total Extractable Metrafenone Residues...............................................................................33 Table 11. Estimated Exposure Concentrations for Metrafenone and Total Metrafenone Residues from Surface Water......................................................................34 Table 12. Input Parameters and Chemical Characteristics of Metrafenone Used in KABAM..............................................................................................35 Table 13. Estimated Concentrations of Metrafenone in Fish (based on metrafenone total residue scenario).....................................................................................35 Table 14. Terrestrial Food
- It em Residu e Estimates for Birds with Metrafenone Proposed Use on Grapes at 0.3 lbs a.i./A (6 apps./year; 14 day app. interval) with a Foliar Dissipation Half

- life default value of 35 Day s .................................................37 Table 15. Terrestrial Food
- It em Residue Estimates for Mammals with Metrafenone Proposed Use on Grapes at 0.3 lbs a.i./A (6 apps./year; 14 day app. interval) with a Foliar Dissipation Half

- life default value of 35 Day s .................................................37 Table 16. Estimated Environmental Concentrations of Metrafenone for Terres trial Plants from Grape Use......................................................................................38 Table 17. Freshwater Fish Acute Toxicity Data.............................................. 39 Table 18. Freshwater Invertebrate Acute Toxicity Data.......................................43 Table 19. Marine/Estuarine Fish Acute Toxicity Data.................. .......................45 Table 20. Marine/Estuarine Invertebrate Acute Toxicity Data................................46 Table 21. Freshwater Fish Chronic Toxicity Data..............................................47 Table 22. Marine/Estuarine Invertebrate Chronic Toxicity Data.............................49 Table 23. Aquatic Plant T oxicity Data...........................................................51Page 114 of 114

Table 24. Avian Acute Toxicity Data............................................................55 Table 25. Mammalian Acute Toxicity Data.....................................................57 Table 26. Terrestrial Invertebrate Acute/Subacute Toxicity Data............................60 Table. 27. Avian Chro nic Toxicity Data.........................................................63 Table. 28. Mammalian Chronic Toxicity Data..................................................65 Table 29. Metrafenone: Chronic Risks to Marine/Estuarine Invertebrates (Application Rate 0.3 lbs a.i./L , 6 Applications/Year).........................................................70 Ta ble 30. Upper Bound Kenaga, Chronic Avian Dietary Based Risk Quotients...........72 Table 31. Chronic RQ Values for Birds Consuming Fish Contaminated by Metrafenone (based on KABAM).................................................................................73 Table 32. Upper Bound Kenaga, Chronic Mammalian Dietary Based Risk Quotients....73 Table 33. Upper Bound Kenaga, Chronic Mammalian Dose
- Based Risk Quotients......74 Table 34. Chronic RQ Values for Mammals Consuming Fish Contaminated by Metrafenone (based on KABAM)................................................................74 Table 35. Listed Species Risks Associated with Direct or Indirect Effects from Metrafenone use on Grapes at the Maximum Proposed Application Rate...................88 Table 36. Number of Endangered Species Potentially Exposed to Metrafenone as used on grapes.................................................................... ..............................94 Table 37. Number of Endangered Species Potentially Exposed to Metrafenone as used on grapes.................................................................................................94