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

Chemical Code: 036602 DP Barcode: 328531, 337542, 338102

MEMORANDUM July 30, 2007

SUBJECT: EFED risk assessment for the registration of the new chemical Mandipropamid

TO: Tony Kish, Risk Manager Registration Division (7505P)

FROM: Fred Jenkins, MS, Biologist Ibrahim Abdel-Saheb, Ph.D., Environmental Scientist Ron Dean, MS, Biologist Environmental Risk Branch II Environmental Fate and Effects Division

THROUGH: Dana Spatz, Branch Chief (acting) Environmental Risk Branch II Environmental Fate and Effects Division (7507P)

EFED has completed the screening level ecologi cal risk assessment for the registration of the new chemical, mandipropamid. The risk assessment has been conducted in accordance with the Agency’s Guidelines fo r Ecological Risk Assessment, and is in compliance with the paper titled “Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs, U.S. E nvironmental Protection Agency” (“Overview Document”) (January 2004).Risks Conclusions

Based on the available data, EFED has dete rmined that mandipropamid’s proposed uses are not expected to pose significant:

• acute or chronic risk to birds

• acute or chronic risk to mammals

• acute risk to aquatic invertebrates

• chronic risk to fish

• acute risk to terrestrial or aquatic plants

EFED is unable to access the acute risk of mandipropamid to fish and mammals, and the chronic risks to aquatic invertebrates because all the fish acute toxi city data are deemed invalid, the mammal acute toxicity data were not submitted, and the chronic aquatic invertebrate toxicity da ta are deemed invalid.

Recommended Label Statements

Based on the use pattern of mandipropamide EFED recommends that the following statement be applied to the mandipropamide end-use product label.

Recommended Label Statements :
“This product may contaminate water through drift of spray in wind. This product has “a potential for runoff” for “sever al months or more after appl ication.” Poorly draining soils and soils with shallow water tables are more prone to produce runoff that contains this product. A level, well maintained vegetati ve buffer strip between areas to which this product is applied and surface water features such as ponds, streams, and springs will reduce the potential for contamination of wa ter from rainfall-runoff. Runoff of this product will be reduced by avoiding applications when rainfall is forecasted to occur within 48 hours.”

“Do not apply directly to water, or to areas where surface water is present or to intertidal areas below the mean high water mark. Do not contaminate water when disposing of equipment washwater or rinsate."

iiUncertainties and Data Gaps

The following provides a summary of th e data gaps in this assessment.

Assessment Data Gaps :

• Fish acute toxicity: All data submitted are invalid

. The studies were invalidated because the dissolved mandipropamid c oncentration was not determined (test solutions contained undissolved particulate test mate rial and the measured concen trations were significantly unstable throughout the testing). Therefore, it is not possible to obtai n accurate toxicity endpoint values that could be us ed for risk assessment purposes.

• Invertebrate chronic toxicity : The submitted study is invalid because reproduction of the daphnids in the solvent control was significan tly lower than in the negative control.

Risk Mitigation Options

Since this screening level risk assessment ha s demonstrated that the proposed use of mandipropamid is not expected to pose any si gnificant risks above th e Agency’s Level of Concern (LOC), EFED does not currently be lieve that any additional risk mitigation measures are needed.

iiiTable of Contents

I. EXECUTIVE SUMMARY .................................................................................................... 7 A. Nature of Chemical Stressor ............................................................................................... 7 B. Potential Risks to Non-Target Organisms .......................................................................... 7 C. Conclusions – Exposure Characterization .......................................................................... 8 D. Conclusions – Effect s Characterization .............................................................................. 8 E. Uncertainties and Data Gaps ............................................................................................... 9 II. PROBLEM FORMULATION ............................................................................................. 11 A. Stressor Source and Distribution ...................................................................................... 11 1. Source and Intensity....... ............................................................................................. 11 2. Physical/Chemical/Fate a nd Transport Properties ........................................................ 11 3. Pesticide Type, Class, and Mode of Action .................................................................. 14 4. Overview of Pesticide Usage ........................................................................................ 14 B. Receptors .......................................................................................................................... 14 1. Aquatic Effects............. ............................................................................................ 15 2. Terrestrial Effects.......... ............................................................................................ 16 3. Ecosystems at Risk......... ........................................................................................... 16 C. Assessment Endpoints ...................................................................................................... 19 D. Conceptual Model ............................................................................................................. 19 1. Risk Hypotheses............ ........................................................................................... 20 2. Diagram...................... ........................................................................................... 20 E. Analysis Plan .................................................................................................................... 21 1. Preliminary Identification of Data Gaps and Methods ................................................. 21 2. Measures to Evaluate Risk H ypotheses and Conceptual Model ................................... 21

a. Measures of Exposure ............................................................................................... 21 b. Measures of Effect .................................................................................................... 22

c. Measures of Ecosystem and Receptor Characteristics ............................................. 22 III. ANALYSIS ........................................................................................................................... 24 A. Use Characterization ......................................................................................................... 24 B. Exposure Characterization ................................................................................................ 25 1. Environmental Fate and Tr ansport Characterization .................................................... 25

a. Summary of Empirical Data ..................................................................................... 25 b. Degradation and Metabolism.................................................................................... 26

c. Transport and Mobility ............................................................................................. 26 d. Field Studies ............................................................................................................. 27 2. Measures of Exposure...... ........................................................................................... 27

a. Aquatic Exposure Modeling ..................................................................................... 27 b. Aquatic Exposure Monitoring and Field Data .......................................................... 28 3. Measures of Terrestrial Exposures ............................................................................... 28

a. Terrestrial Exposure Modeling ................................................................................. 28 b. Terrestrial Residue Studies ....................................................................................... 32 C. Ecological Effects Characterization .................................................................................. 32 1. Aquatic Effects Characterization .................................................................................. 32

iva. Aquatic Animals ....................................................................................................... 36 (1). Acute Effects ..................................................................................................... 36 (2). Chronic Effects ................................................................................................. 37 (3). Sublethal Effects ............................................................................................... 39 (4). Field Studies ..................................................................................................... 39 b. Plants Inhabiting Aquatic Areas ............................................................................... 39 2. Terrestrial Effects Characterization .............................................................................. 40

a. Terrestrial Animals ................................................................................................... 43 (1). Acute Effects ..................................................................................................... 43 (2). Chronic Effects ................................................................................................. 44 (3). Sublethal Effects ............................................................................................... 45 (4). Field Studies ..................................................................................................... 46 b. Terrestrial Plants ....................................................................................................... 46 IV. RISK CHARACTERIZATION ............................................................................................ 48 A. Risk Estimation – Integration of Exposure and Effects Data ........................................... 48 1. Non-Target Aquatic Animals and Plants ..................................................................... 48

a. Acute Risk to Aquatic Animals ................................................................................ 48 b. Chronic Risk to Aquatic Animals ............................................................................. 49

c. Risks to Aquatic Plants ............................................................................................. 50 2. Non-Target Terrestrial Animals ................................................................................... 50

a. Acute Risk to Mammals and Birds ........................................................................... 50 b. Chronic Risk to Birds and Mammals ........................................................................ 50

c. Risk to Terrestrial Invertebrates ............................................................................... 51 3. Non-target Plants Inhabiting Te rrestrial and Semi-Aquatic Areas ............................... 51 B. Risk Description ............................................................................................................... 52 1. Risks to Aquatic Organisms ......................................................................................... 52 2. Risks to Terrestrial Organisms ................................................................................. 52

a. Terrestrial Animals (Mammals and Birds) ............................................................... 52 b. Insects ....................................................................................................................... 53

c. Plants ......................................................................................................................... 53 3. Review of Incident Data... ........................................................................................... 53 4. Endocrine Effects.......... ............................................................................................. 53 C. Federally Threatened and Endange red (Listed) Species Concerns .............................. 54 1. Action Area............................................................................................................. 54 2. Taxonomic Groups Potentially at Risk ......................................................................... 54

3. Probit Dose Response Relationship ............................................................................. 55 4. Indirect Effects Analysis.............................................................................................. 55 5. Critical Habitat.............. ............................................................................................ 55 D. Description of Assumptions, Limitations, Uncertainties, Strengths and Data Gaps ........ 56 1. Assumptions, Limitations, Uncertainties, Stre ngths and Data Gaps Related to Exposure for All Taxa....................... ............................................................................................. 56 2. Assumptions, Limitations, Uncertainties, Stre ngths and Data Gaps Related to Exposure for Aquatic Species............... ........................................................................................... 56

vvi a. GENEEC Standard Runoff Model ............................................................................ 56 3. Assumptions, Limitations, Uncertainties, Stre ngths and Data Gaps Related to Exposure for Terrestrial Species............ ........................................................................................... 57

a. Residue Concentration .............................................................................................. 57 b. Variation in Habitat and Dietary Requirements ....................................................... 57

c. Variation in Diet Composition .................................................................................. 57 d. Exposure Routes Other than Dietary ........................................................................ 58

e. Incidental Soil Ingestion Exposure ........................................................................... 58 f. Inhalation Exposure .................................................................................................. 58
g. Dermal Exposure ...................................................................................................... 58 h. Drinking Water Exposure ......................................................................................... 67 i. Dietary Intake – Differences Betw een Laboratory and Field Conditions ................ 59 4. Assumptions, Limitations, Uncertainties, Stre ngths and Data Gaps Related to Effects Assessment......................... ........................................................................................... 60

a. Age Class and Sensitivity of Effects Thresholds ...................................................... 60 b. Use of the Most Sensitive Species Tested ................................................................ 61 V. REFERENCES ..................................................................................................................... 627 

### I. EXECUTIVE SUMMARY

A. Nature of Chemical Stressor

Mandipropamid is a new fungicide intended for th e control of foliar oomycete pathogens in a range of crops. Mandipropamid’s mode of action is as a preven tive foliar fungicide that is effective at inhibiting spore germination, myce lial growth and sporulation. Mandipropamid is absorbed to the plant wax layer, provi ding resistance to rainwater wash-off. Once mandipropamid is taken up by the plant tissue, tr anslaminar mobility provides protection of the opposition leaf surface.

In accordance with the registrant submitted la bel, the proposed maximum use rate for all crops is four applications of 0.13 lbs a.i./a cre with 7-10 days be tween each application. Mandipropamid is formulated as a suspension concen trate that requires the use of an external adjuvant (such as a non-ionic surfactant, crop oil concentrate, silicone based, or blend methylated or ethylated seed oi l) to enhance f ungicidal activity.

C. Potential Risks to Non-Target Organisms

Based on the available data, EFED has determ ined that mandipropamid’s proposed uses are not expected to pose significant:

• acute or chronic risk to birds

• acute or chronic risk to mammals

• acute risk to aquatic invertebrates

• chronic risk to fish

• acute risk to terrestrial or aquatic plants

EFED is unable to access the acute risk of ma ndipropamid to fish and the chronic risks to aquatic invertebrates because all the fish acute toxicity data are d eemed invalid and the chronic aquatic invertebrate toxicity data are deemed invalid as well.8 Table 1 summarizes the conclusions of this a ssessment in regards to endangered species.

Table 1. Summary of Screening Level Risk Assessment Findings in Regards to Direct and Indirect Effects of Mandipropami d to Federally Listed Species. Listed Taxon Direct Effects Indirect Effects Terrestrial and semi-aquatic plants - monocots No No Terrestrial and semi-aquatic plants - dicots No No Terrestrial invertebrates No No Birds No No Terrestrial-phase amphibians No No Reptiles No No Mammals No Aquatic non-vascular plants No No

Aquatic vascular plants No No Freshwater fish No data No Aquatic-phase amphibians No No Freshwater crustaceans No No Mollusks No No Marine/estuarine fish No No Marine/estuarine crustaceans No No

C. Conclusions – Exposure Characterization

Aquatic and terrestrial species may be e xposed to mandipropamid through its proposed agricultural uses. Mandipropamid is considered to be persistent in the environment. Mandipropamid appears to be stable to hydrolys is at environmental pH (pH range 5–9) but susceptible to photolysis in soil and water. Based on its vapor pressure and Henry’s Law constant, volatilization from water and soil are not expected to be important environmental fate processes. Mandipropamid is moderately m obile in soil and has the potential to leach into ground water. The stressors of concern ar e the parent chemical, mandipropamid, and its’ degradates SYN500003 and SYN504851 both of whic h were identified by the Human Health Effects Division (HED) as t oxic degradates of concern.

D. Conclusions – Effects Characterization

Fish Acute Toxicity

No acceptable fish acute toxicity data are ava ilable. The studies submitted are invalid (See Appendix E for further details).

Fish Chronic Toxicity

The registrant submitted a freshwater fish chr onic toxicity study that demonstrates chronic exposure to technical mandipropamid causes si gnificant decreases to fish growth at a9 NOAEC and LOAEC concentration of 0.21 ppm and 0.45 ppm respectively (See Appendix E for further details).

Aquatic Invertebrate Toxicity

The registrant submitted aquatic invertebrate acute toxicity studies demonstrate that technical mandipropamid is moderately toxic to freshwater invertebrates and very highly to moderately toxic marine/estuarine invertebrates (See Appendix E for further details).

Aquatic Invertebrate Chronic Toxicity

The registrant submitted aquatic invertebrate ch ronic toxicity data are invalid (See Appendix E for further details).

Plant Toxicity

i. Terrestrial Plants

The registrant submitted a vegetative vigor terrestrial plant toxicity study and a seedling emergence terrestrial plant toxicity study. Bo th studies demonstrate that the measured endpoints did not reach the EC 25 toxicity level in any of speci es tested with the exception of the carrot species, which rendered unreliable results in the seedling emergence study (See Appendix E for further details). The monoc ot and dicot NOAEC values for the seedling emergence studies are 0.660 lbs a.i./A and 0.165 lbs a.i./A respectivel y. The monocot and dicot NOAEC values for the vegetative vigor studies are 0.198 lbs a.i./A and 0.792 lbs a.i./A respectively.

ii. Aquatic Plant Toxicity

The registrant has submitted a nonvascular aquatic plant toxicity study testing the effect of mandipropamid on the green alga, Pseudokirchneriella subcapitata (MRID 468001-21) and a vascular aquatic plant toxicity study te sting the effect of mandipropamid on Lemna gibba (MRID 468001-19). The green alga l study demonstrates an EC 50 > 2.5 ppm a.i. for all endpoints measured and a NOAEC of 1.3 ppm ba sed on biomass. The Lemna gibba study demonstrates an EC 50 > 7.9 ppm a.i. for all endpoints measured and a NOAEC of 1.3 based on growth rate. (See Appendix E for further details).

E. Uncertainties and Data Gaps

The following provides a summary of th e data gaps in this assessment.

Assessment Data Gaps :

• Fish acute toxicity: All data submitted are invalid

. The studies were invalidated because the dissolved mandipropamid concentration was not10 determined (test solutions contained undi ssolved particulate test material and the measured concentrations were significantly unstable throughout the testing). Therefore, it is not possibl e to obtain accurate toxicity endpoint values that could be used for risk assessment purposes.

• Invertebrate chronic toxicity: The submitted study is invalid because reproduction of the solvent control daphni ds was significantly lower than that of negative control daphnids.11 II. PROBLEM FORMULATION

A. Stressor Source and Distribution

1. Source and Intensity

Mandipropamid, a fungicide (proposed name Revus TM ), is specifically intended to control foliar oomycete pathogens in a range of crops. Mandipropamid is not currently registered for agricultural use in the U.S. This chemical is applie d to crops via ground and aerial methods. This assessment focuses on the proposed uses of mandipropamid on brassica vegetables, bulb vegetables, cucurbits, fruiting vegetables, gr apes, leafy vegetables, potatoes, tomatoes, tuberous and corm vegetables.

2. Physical/Chemical/Fate and Transport Properties

Mandipropamid is considered to be persiste nt in the environment. The major route of dissipation is degradation under aerobic aquatic conditions. Mandipropamid degrades to several intermediatery degradation products . The transformation products are ultimately degraded to non-extractable residues and car bon dioxide. Mandipropamid is moderately mobile and some of its metabolites are mobile to highly mobile in so ils, and therefore have the potential to leach into ground water. Mandipropamid can reach surface waters via spray drift and rainfall events that cause runoff. The important physical and chemical properties for mandipropamid are summarized in Table 2 followed by its chemical structure ( Figure 1 ).12 Table 2. Chemical and Physical Properties for Mandipropamid
CAS number 374726-62-2 MRID 46800009 SMILES notation Clc1ccc( cc1)C(OCC#C)C(=O)NCC c1ccc(c(c1)OC)OCC#C (ISIS v2.3/Universal SMILES). C1=C(Cl)C=CC(C(OCC#C)C(=O) NCCC2=CC=C(OCC#C)C(OC)=C 2)=C1 (EPI Suite, v3.12 SMILES). C1c(ccc(c1)C(C(NCCc1ccc(c(c1)O C)OCC#C)=O)OCC#C)C1 MRID 46800009

Molecular weight 411.9 MRID 46800009 Molecular formula C 23 H 22 ClNO 4 MRID 46800009 Vapor pressure 3.52 X 10 -8 Torr MRID 46800007&8 Solubility in water (pH 7, 20 o C) 2.3 ppm MRID 46800009 Henry’s Law constant 8.293E-09 (atm.m3/mole) Calculated from Vp, Solubility, and M.wt Log K ow 3.13 MRID 46800007&8 pK a Not reported Hydrolysis half-life (days) for pH 5, 7, and 9 Stable at pH 5, 7, and 9 MRID 46800007&8

Aquatic photolysis half-life 0.63 -1.1 days MRID# 46800009,10,13,14 Soil photolysis half-life 16.4 – 24 days MRID 46800015,16,17 Aerobic soil metabolism half-life 72.2 days (sandy loam) 26.1days (silt loam) 78 - 103 days (silt loam) 32.4 days (loan, silt loam) 51.3 days (sandy clay loam, ) 90 days (loam) 83.5 (loamy sand) MRID 46800020,21 MRID 46800022 MRID 46800024,25 MRID 46800027 MRID 46800028

Anaerobic soil metabolism half-life 151 MRID 46800022 K oc (adsorption) 782 (Loam/silt loam ) 1294 (Loamy sand ) 1067 (Silty clay loam ) 1064 (Silt loam )

694 (sandy loam) 405 (loamy sand) 624 (loamy sand) MRID 46800038,39

MRID 46800040,41

Aerobic aquatic metabolism halflife 17.7 days MRID 46800030,31

Anaerobic aquatic metabolism halflife No data available Unacceptable study (MRID 466800033,34)13 Cl O

O N CH

2 C CH

C H 2 C H 2

O O CH 3

C H 2 C CH

Mandipropamid

Cl O

O OH CH 2 C CH 3

SYN500003

Cl O

O OH CH

2 C

SYN504851

Figure 1. Chemical Structures of Mandi propamid and its major degradates.14 3. Pesticide Type, Class, and Mode of Action

Mandipropamid belongs to the new mandelami de chemical class of fungicides. Mandipropamid’s mode of action is as a preventive foliar fung icide that is effective at inhibiting spore germination, mycelial growth an d sporulation. Mandipropamid is absorbed to the plant wax layer, providing resistance to rainwater wash-off. Once mandipropamid is taken up by the plant tissue, translaminar mob ility provides protection of the opposition leaf surface.

4. Overview of Pesticide Usage

The proposed label specifies that mandipropami d is a ground and aeriall y applied fungicide formulated as a suspension concentrate that requires the use of an external adjuvant.

The proposed label specifies that the maximu m amount of mandipropamid that may be used per growing season is 0.52 lbs a. i./acre which may be divided in to 4 applications of 0.13 lbs a.i./acre with a 7-day minimum in terval between each application.

Actual pesticide usage data are not available si nce this chemical is cu rrently not registered for use in the US. Because this chemical is proposed for use on field brassica vegetables, bulb vegetables, cucurbits, frui ting vegetables, grapes, leafy vegetables, potatoes, tomatoes, tuberous and corm vegetables, the current geogr aphic distribution of these crops is expected to be generally representative of pot ential mandipropamid application areas.

B. Receptors

Each assessment endpoint requires one or mo re measures of ecological effect, which are defined as changes in the attrib utes of an assessment endpoint itself or changes in a surrogate entity or attribute in response to exposure to a pesticide. Ec ological measures of effect for the screening level risk assessment are based on a suite of registrant-submitted toxicity studies performed on a limited number of organisms in broad groupings listed in Table 3

.

Table 3. Taxonomic Groups and Test Speci es Evaluated for Ecological Effects in Screening-Level Risk Assessments Taxonomic Group Example(s) of Representative Species Birds a Mallard duck ( Anas platyrhynchos ) Bobwhite quail ( Colinus virginianus ) Mammals Laboratory rat ( Rattus norvegicus ) Freshwater fish b Bluegill sunfish ( Lepomis macrochirus ) Rainbow trout ( Oncorhynchus mykiss ) Freshwater invertebrates Water flea ( Daphnia magna ) Estuarine/marine fish Sheepshead minnow ( Cyprinodon variegatus ) Estuarine/marine invertebrates Eastern oyster ( Crassostrea virginica ) Mysid shrimp ( Americamysis bahia ) Terrestrial plants Monocot and dicot Insects Honeybee15 Table 3. Taxonomic Groups and Test Speci es Evaluated for Ecological Effects in Screening-Level Risk Assessments Taxonomic Group Example(s) of Representative Species Aquatic plants Bluegreen alga Green alga Saltwater diatom Duckweed ( Lemna gibba )

a Birds are considered surrogates for amphibians (terrestrial phase) and reptiles when no data are available.
b Freshwater fish may be surrogates for amphibian s (aquatic phase) when no data are available.
Within each of these very broad taxonomic gr oups, an acute and/or chronic endpoint is selected from the available test data. A comple te discussion of all toxi city data available for this risk assessment and the resulting measur es of effect selected for each taxonomic group are included in Appendix E.

1. Aquatic Effects

Direct application of mandipr opamid to streams, lakes, and ponds is prohibited by the product label. Immediately following applica tion, the highest mandipropamid residue levels are expected to be located in surface waters adja cent to treated agricultu ral fields due to spray drift at the time of application and/or from r unoff after a rain event. Mandipropamid may be transported off the field in runoff for several months after applicati on. Exposure estimates for this screening level risk assessment focuses on the total residues for aquatic concentrations of the parent, mandipropami d, and its degradates of toxic concern SYN500003 and SYN504851. These degradates, wh ich were identified in the suite of environmental fate studies, are according to the Health Effects Divi sion, toxic degradates also found in residue studies. Fi sh, amphibians, and aquatic inve rtebrates that live in aquatic environments are potentially exposed to mandi propamid residues in surface water by direct contact of their integument (cove ring of the body or a part such as skin, gill membranes, cuticle, etc.) and via uptake through their gill s or integument. Assessment endpoints were selected to assess reduced survival, growth, and reproduction in these taxonomic groups from combined direct contact with integument and up take across the gill or integument. Because toxicity data for amphibians are rarely available, fish were used as a surrogate to assess risks to aquatic-stage amphibians (USEPA 2004). Aqua tic plants are also potentially exposed by contact of their outer surface area with mandipr opamid residues in surface water or through sorption and uptake through r oots or across cell walls.

Aquatic animals may also be exposed to mandipr opamid residues in sediment or in their diet (i.e., detritus, aquatic plants, and/or prey). Sediment residues of mandipropamid and its degradates may potentially occur because of er oded soil in runoff depositing out to sediment and from the chemicals partitioning to sediment from water. Food chain transfer has the potential to occur where higher trophic level organisms feed on organisms that have taken up mandipropamid from surface water through their g ills or integument or on organisms or detrital matter that have sorbed mandipropamid. No studies have been submitted regarding the potential for bioconcen tration in aquatic orga nisms. Although the K oc values indicate that16 mandipropamid residues will partition to sediment to some degree, the log K ow of 3.13 indicates that bioconcentration shoul d not be of particular concern.

Leaching (infiltration/percolation) may result in transport of mandipropamid through the soil column into ground water which may, in some circumstances, flow into a surface water body. The mobility of mandipropamid in soil is considered moderate based on batch adsorption experiments conducted in seven soils.

2. Terrestrial Effects

The highest mandipropamid residue levels are expected to be lo cated in the surface soil and on foliage (e.g., short and tall grasses, broadl eaf weeds), seeds, and insects on the treated agriculture field immediatel y following ground spraying. While spray drift may result in transport of mandipropamid to off-target field surface soil, foliage, and insects, the highest concentrations for these media are still expected to be those in the treated field. Birds, mammals, reptiles, and amphibians that ingest foliage, insects, and/or soil invertebrates from either the treated area or from spray drift impacted areas are potentially exposed to mandipropamid residues in their diet. Endpoint s will be included that assess reduced survival, growth, and reproduction in thes e taxonomic groups from dietary exposure. Because toxicity data for reptiles and terrestria l-phase amphibians are ra rely available, risk assessment results for birds will be used as su rrogates to assess risks to reptiles and terrestrial-phase amphibians (USEPA 2004).

Mandipropamid may reach off-fiel d terrestrial or riparian/wet land vegetation environments in spray drift at the time of application. Following a rain event, mandipropamid may also reach off-field terrestrial or riparian/wetland vegetation environments in sheet and channel flow runoff.

3. Ecosystems at Risk

Ecosystems potentially at risk are expressed in te rms of the selected assessment endpoints ( Table 4 ). The typical assessment endpoints for scr eening-level pesticide ecological risks are reduced survival, and reproducti ve and growth impairment for both aquatic and terrestrial animal species. Aquatic animal species of pot ential concern include freshwater fish and invertebrates, estuarine/marine fish and inve rtebrates, and amphibian s. Terrestrial animal species of potential concern incl ude birds, mammals, and benefi cial insects. For both aquatic and terrestrial animal species, direct acute a nd direct chronic exposur es are considered. In order to protect threatened and endangered spec ies, all assessment endpoints are measured at the individual level. Although endpoints are meas ured at the individual level, they provide insight about risks at higher levels of biological organizati on (e.g., populations and communities). For example, pesticide effects on individual survivorship have important implications for both population rates of increase and habitat carrying capacity.

For terrestrial and semi-aquatic plants, the sc reening assessment endpoint is the perpetuation of populations of non-target sp ecies (crops and non-crop plan t species). Ex isting testing17 requirements have the capacity to evaluate emergence of seedlings and vegetative vigor. Although it is recognized that th e endpoints of seedling emergence and vegetative vigor may not address all terrestrial and semi-aquatic plant life cycle components, it is assumed that impacts at emergence and in active growth have the potential to impact individual competitive ability and reproductive success. Fo r aquatic plants, the assessment endpoint is the maintenance and growth of standing crop or biomass. Measurements for this assessment endpoint focus on cell density, growth rates, and biomass in non-vascular plants (i.e., freshwater algae) and frond number, growth rate, and biom ass in aquatic vascular plants (duckweed).

The ecological relevance of selecting the above-mentioned assessment endpoints is as follows: (1) complete exposure pathways exist for these receptors; (2) the receptors may be potentially sensitive to pesticides in affect ed media and in residues on plants, seeds, and insects; and (3) the receptors co uld potentially inhabit areas wh ere pesticides are applied, or areas where runoff and/or spray drift may imp act the sites because suitable habitat is available.

Table 4. Summary of Assessment Endpoints a nd Measures of Effect in Screening Level Risk Assessment Assessment Endpoint Measures of Effect 1. Abundance (i.e., survival, reproduction, and growth) of individuals and populations of birds in close proximity to sites 1a. Mallard duck (at least) acute oral LD 50 1b. Mallard duck and bobwhite quail subacute 5-day dietary LC 50 1c. Mallard duck (at least) reproduction NOAEL (e.g., number of eggs laid, set, cracked, etc.) 2. Abundance (i.e., survival, reproduction, and growth) of individuals and populations of mammals in close proximity to sites 2a. Laboratory rat (at least) acute oral (single dose) LD 50 2b. Laboratory rat (at least) chronic (reproductive) NOAEC or NOAEL 3. Survival and reproduction of individuals and communities of freshwater fish and invertebrates in close proximity to sites 3a. Rainbow trout and bluegill sunfish (at least) acute 96-hr LC 50 3b. Rainbow trout or bluegill sunfish (preferred species tested that of the more acutely sensitive species tested) chronic early life-stage or life-cycle NOAEC (e.g., number hatched, time to hatch, mortality, growth of young) 3c. Daphnia magna (at least) acute 48-hr EC 50 (or 96-hr LC 50 for other invertebrates) where effect measured is surrogate for death 3d. Daphnia magna (at least) chronic reproductive NOAEC (e.g., number of young produced, time to first brood release, parental survival, parental growth)18 Table 4. Summary of Assessment Endpoints a nd Measures of Effect in Screening Level Risk Assessment Assessment Endpoint Measures of Effect 4. Survival and reproduction of individuals and communities of estuarine/marine fish and invertebrates in close proximity to sites 4a. Atlantic silverside or sheepshead minnow (at least) acute 96-hr LC 50 4b. Eastern oyster (at least) acute 96-hr EC 50 where the effect measured is shell deposition or embryo/larval fertilization, survival, and normal shell development 4c. Pink shrimp or mysid shrimp (at least) acute 96-hr LC 50 or EC 50 where the effect measured is a surrogate for mortality 4d. Fish (prefer species that matches the most acutely sensitive fish tested) early life stage or life cycle NOAEC (e.g., number hatched, time to hatch, growth of young, overall survival) 4e. Mysid shrimp (at least) chronic NOAEC 5. Survival of beneficial insect populations in close proximity to sites 1. Honey bee acute contact LD 50
6. Survival and growth of terrestrial plants in close proximity to sites 6a. Monocot and dicot seedling emergence EC 25 6b. Monocot and dicot seedling emergence EC 05 or NOAEC 6c. Monocot and dicot vegetative vigor EC 25 6d. Monocot and dicot vegetative vigor EC 05 or NOAEC 7. Standing crop or biomass and growth of aquatic plants in close proximity to sites 7a. Green and blue-green alga (at least) EC 50 7b. Freshwater and saltwater diatom and duckweed (at least duckweed) acute EC 50 7c. Green and blue-green algae, a freshwater and saltwater diatom and duckweed (at least) EC 05 or NOAEC
LD 50 = Lethal dose to 50% of the test population. LC 50 = Lethal concentration to 50% of the test population. EC 50 /EC 25 /EC 05 = Effect concentration to 50/25/5% of the test population. IC 25 /IC 05 = 25/5% Inhibitory concentration. NOAEC = No observed ad verse effect level. LOAEC = Lowest observed adverse effect level.19 C. Assessment Endpoints

Assessment endpoints are defined as “explicit expr essions of the actual environmental value that is to be protected”. De fining an assessment endpoint invo lves two steps: (1) identifying the valued attributes of the environment th at are considered to be at risk; and (2) operationally defining the assessment endpoint in terms of an ecological entity (i.e., a community of fish and aquatic invertebrate s) and its attributes (i.e., survival and reproduction). Therefore, selection of the asse ssment endpoints is based on valued entities (i.e., ecological receptors), the ecosystems potentially at risk, the migration pathways of pesticides, and the routes by which ecologica l receptors are exposed to pesticides. The selection of clearly defined assessment endpoints is important because they provide direction and boundaries in the risk assessment for addr essing risk management issues of concern.

This ecological risk assessment considers ma ximum application rates of mandipropamid to fields that have vulnerable soils, maximum nu mber of applications, and minimum intervals for uses on representative crops grown on runoff prone soils to estimate exposure concentrations. In addition, th is assessment is not intended to represent a site- or timespecific analysis. Instead, this assessment is intended to represent high-end exposures at a national level. Likewise, the most sensitive toxicity measures of effect are used from surrogate test species to estimate treatment -related direct effects on acute mortality and chronic reproductive, growth, and survival asse ssment endpoints. Toxicity tests are intended to determine effects of mandipropamid exposur e on birds, mammals, fish, terrestrial and aquatic invertebrates, and pl ants. These tests include shor t-term acute, subacute, and reproductive studies and are typi cally arranged in a hierarchical or tiered system that progresses from basic laboratory te sts to applied field studies. Th e toxicity studies are used to evaluate the potential of mandipropamid to cau se adverse effects, to determine whether further testing is required, and to determine th e need for precautionary label statements to minimize the potential adverse effects to non-target animals and plants (CFR 40 §158.202, 2002a). A summary of measures of effects selected to characte rize potential ecological risks associated with exposure to mandipropamid is provided in Table 4

. D. Conceptual Model

In order for a chemical to pose an ecologica l risk, it must reach ecological receptors in biologically significant concen trations. An exposure pathway is the means by which a contaminant moves in the environment from a source to an ecological receptor. For an ecological exposure pathway to be complete, it must have a source, a release mechanism, an environmental transport medium, a point of exposure for ecological receptors, and a feasible route of exposure. In addition, the potentia l mechanisms of transformation (i.e., which degradates may form in the environment, in which media, and how much) must be known, especially for a chemical whose metabolites/deg radates are of greater toxicological concern. In this assessment the parent, mandipropa mid, and its degradates of toxic concern, SYN500003 and SYN504851 (as identified by HED) are quantitatively a ssessed together as total residues of mandipropamid. The assessmen t of ecological exposure pathways includes an examination of the source and potential migration pathwa ys for constituents, and the20 determination of potential exposure routes (e.g., inges tion, inhalation, and dermal absorption).

1. Risk Hypotheses

Risk hypotheses are specific assumptions about potential adverse effects (i.e., changes in assessment endpoints) and may be based on theory and logic, empirical data, mathematical models, or probability models (USEPA 2004). Fo r this assessment, the risk is stressorinitiated, where the stressor is the release of mandipropa mid to the environment. The following risk hypothesis is presumed for this screening level assessment:

The use of mandipropamid as an fung icide in agricultural settings on field brassica vegetables, bulb vegetables, cucurbits, frui ting vegetables, grapes, leafy vegetables, potatoes, tomatoes, tuberous and corm vegetabl es involves situations where terrestrial and/or aquatic animals and plants may be exposed to the chemical. Based on information on persistence, mode of action, direct toxicity and potential indirect effects to trophic food webs, EFED assumes that mandipropamid t ogether with its degradates of concern, SYN500003 and SYN504851 have the potential to cause reduced survival and reproductive impairment to terres trial and aquatic animals and plants.

2. Diagram

The source and mechanisms of release of mandipropamid ar e ground and aerial application to agricultural crops. The conceptual model a nd subsequent analysis of exposure and effects are all based on mandipropamid and its degrad ates of concern, SYN500003 and SYN504851. Surface water runoff from the areas of application is assumed to follow topography. Additional release mechanisms include spray drift and wind erosion, which may potentially transport contaminants into the air. Pote ntial emission of volatile compounds is not considered as a viable release mechanis m for mandipropamid, because vapor pressure information suggests that volatiliz ation is not expected to be a significant route of dissipation. The conceptual model shown in Figure 2 depicts the potential source, release mechanisms, abiotic receiving media, and biological re ceptor types.21 Figure 2. Conceptual Model Depicting Ecol ogical Risk Based on the Proposed Mandipropamid Application

Application of Mandipropamide, to Any of Its Proposed Use Crops Stressor

Source: Transport Pathway Direct Ground Deposition Spray Drift Volatilization Wind Suspension Runoff/ Erosion Leaching

Source: Exposure Media Terrestrial Food Residues (foliage, fruit, Insects;) Upland Soil And Foliage Riparian/Wetland Foliage/Soil Surface Water Sediment Groundwater

Exposure Point Direct Contact And Ingestion Direct Contact/ Root Uptake Uptake/Adsorption Gill/Integument Uptake

Receptors Terrestrial Vertebrates and Invertebrates Terrestrial Upland Plants Riparian/Wetland Plants Aquatic Plants Aquatic Invert and Vertebrates

Direct Effects Terrestrial Animal •Lethality •Reproductive/ developmental Effects •Other adverse sublethal effects Non-Target Plants •Plant growth abnormalities •Lethality •Developmental/reproductive effects Plant Population Reduced Population growth Aquatic Animals and Plants •Effects to survival, growth, and Reproduction •Reproduction in cell density/biomass in aquatic plants • Other adverse sublethal effects

Indirect Effects Altered Terrestrial Community Assemblages: Reduced food supply and edge habitat availability Altered Aquatic Community Assemblages: Effects to riparian habitat availability Effects to

E. Analysis Plan

1. Preliminary Identification of Data Gaps and Methods

Based on EFED’s review of the currently ava ilable data, the identified data gaps are as follows:

• acceptable fish acute toxicity data (current studies are invalid)

• acceptable invertebrate chronic toxicity data (current studies are invalid)

2. Measures to Evaluate Risk Hypotheses and Conceptual Model

a. Measures of Exposure

The proposed uses for mandipropamid are for brassica vegetables, bulb vegetables, cucurbits, fruiting vegetables, grapes, leafy vegetables , potatoes, tomatoes, tuberous and corm vegetables. Since mandipropamid is currently not registered for use on these crops, no22 statistics exist regarding the am ount of mandipropamid that has been applied to these crops in the past. However, the present geographic di stribution for these proposed site uses are expected to generally represent pote ntial mandipropamid application areas.

For agricultural uses, exposure concentrations for aquatic ecosystem assessments will be estimated based on EFED’s aquatic Tier I model GENEEC. Among the major degradates identified in various fate studi es (CGA380778, NOA458422, CGA380775, SYN500003, SYN536638, and SYN504851), only SYN500003 and SYN504851 were identified by the Office of Pesticides Programs Human Health E ffects Division (HED) to be of toxic concern. There are no available ecotoxicity data for these two degradates. This assessment will assume that these degradates have similar toxic ity as the parent. Total residue data were used in EFED’s aquatic Tier I model GENEEC.

Residues in potential dietary sources (e.g., vegetation and inse cts) for mammals and birds will be estimated using the Tier I model T- REX Version 1.3.1 (USEPA 2006a). This model provides estimates of concentrations (maxim um, or upper bound, and average) of chemical residues on the surfaces of different types of folia ge that may be sources of dietary exposure to avian, mammalian, reptilian, or terrestrial-phase amphibian receptors. The surface residue concentration (ppm) is estimated by multiply ing the application rate (pounds active ingredient per acre) by a value specific to each food item. For both mammals and birds, three animal body weight classes are consider ed. The T-REX model will be run using the maximum application rate for all proposes uses (which is 4 a pplications of 0.13 lbs a.i./acre with a minimum of 7 days between each application).

Exposure to terrestrial and se mi-aquatic (wetland) plants will be estimated using the TerrPlant model Version 1.2.2 (USEPA 2006b). The TerrPlant model estimates risk quotients for non-target monocot and dicot plants that ma y be exposed to pesticides applications via runoff and/or spray drift to terre strial plants inhab iting dry and semi-aquatic (wetland) areas. RQs are calculated using the EC 25 value for non-threatened/endangered plants and the EC 05 or NOAEC value for threat ened/endangered plants.

b. Measures of Effect

Measures of ecological effects are obtained from a suite of registrant-submitted guideline studies conducted with a limited number of surrogate species. Registrant-submitted data suitable for quantitative risk as sessment are available for acute exposure of birds, terrestrial invertebrates, freshwater and marine/estuarine invertebrate, and terr estrial plants, and for chronic exposure to birds, mammals, and fr eshwater fish. A generic summary of the measures of effect based on pe sticide toxicity studies for di fferent ecological receptors and effect endpoints (acute/c hronic) is given in Table 4

. c. Measures of Ecosystem and Receptor Characteristics

For the assessments using the Tier I aquatic mo del GENEEC and the Tier I terrestrial models T-REX and TerrPlant, the ecosystems that are modeled are intended to be generally23 representative of any aquatic or terrestrial ecosystem a ssociated with areas where mandipropamid could be used. For aquatic asse ssments, fish and aquatic invertebrates in both freshwater and estuarine/mari ne environments are represente d, as well as aquatic plants. For terrestrial assessments, three different size classes of small birds and mammals are represented, along with four pot ential foraging categories, as well as two terrestrial plant groups (upland plants and plants growing in semi-aquatic areas).24 

### III. ANALYSIS

A. Use Characterization

The purpose of the ecological risk assessment is to assist the Agency in evaluating the actions needed, if any, to address ecological risk s associated with uses of the new fungicide, Revus TM (proposed name mandipropamid), for use on brassica vegetables, bulb vegetables, cucurbits, fruiting vegetables, grapes, leafy ve getables, potatoes, tomatoes, tuberous and corm vegetables. This chemical is to be applied on commercial or farm plantings via ground or aerial applications. It re quires the use of an external adjuvant (such as a non-ionic surfactant, crop oil concentrate, silicone based, or blend) to enhance fungicidal activity.

Mandipropamid is a new chemical, currently unr egistered for use. Therefore, there is no current chemical usage information availa ble in the National Center for Food and Agricultural Policy (NCFAP) pesticide use databa se or the U.S. Department of Agriculture National Agriculture Statistics Service (NASS) chemical use database.

The proposed label specifies that mandipropa mid is intended for the control of foliar oomycete pathogens in a ra nge of crops including Plasmopara viticola in grapes, Phytophthora infestans in potatoes and tomatoes and Pseudoperonospora cubensis in cucurbits

The proposed label specifies that the maximum amount of the active ingredient that may be applied in a single growing season is 0.52 lbs a.i./acre. Accordi ng to the proposed label, this application amount may be divided into 4 appl ications of 0.13 lbs a.i./acre with 7 day intervals between each application.

Product information: Product Name: Mandipropamid Fungi cide (proposed name Revus TM ) Active Ingredients: Mandipropamid.................................................................................................................. ..... 23.3% Inert ingredients .............................................................................................................. ........ 76.7% Total .......................................................................................................................... ............... 100% (CAS Number 374726-62-2)25 Table 5. Application Rates of Mandipropamid

Crops Disease Control Application Rate (lbs a.i./acre) Maximum No. Applications per Season Interval Restrictions Brassica vegetables, bulb vegetables, cucurbits, fruiting vegetables,
grapes, leafy vegetables, potatoes, tomatoes, tuberous and corm vegetables foliar oomycete pathogens in a range of crops including Plasmopara viticola in
grapes, Phytophthora infestans 0.13 4 7-day minimum interval between applications Do not apply: 1. More than 32 fl oz of product /A/Season 2. Within 1 day of harvest for brassica, leafy vegetables, fruiting vegetables,
tomatoes. 3. Within 7 days of harvest for bulb vegetables. 4. Within 14 days of harvest for potatoes,
grapes

B. Exposure Characterization

1. Environmental Fate and Transport Characterization

Data were submitted regarding the hydrolysis, photolysis, biodegradation, soil adsorption properties, and field dissipati on of mandipropamid. These data are sufficient to characterize the transport, partitioning, mobility, and degradation of mandipropamid and several of its major metabolites in the environment. Th e physical and chemical properties used to characterize the environmental fate of mandipropamid were summarized in Table 2

. Chemical names and structures of the metabolit es discussed below are provided in Appendix A.

a. Summary of Empirical Data

Registrant submitted studies indicate that mandipropamid is persistent in the environment, under aerobic aquatic conditions. Mandipropamid appears to be stable to hydrolysis at environmental pH (pH range 5–9) but susceptible to photolysis in soil and water. Due to its vapor pressure and Henry’s Law constant, volati lization from water and soil is not expected to be an important environmental fate proce ss. Mandipropamid and several of its metabolites can be mobile in soil and have the po tential to leach into ground water.26 b. Degradation and Metabolism

Mandipropamid did not undergo abiotic hydroly sis in pH 5, 7, and 9 aqueous buffered solutions maintained at 25 °C over the c ourse of a 30 day incubation period (MRID 46800007&8). The environmental photolysis half-lives of mandipropamid in pH 7, 25°C aqueous solution were estimated as 0.63-1.1 days (MRID# 46800009,10,13,14). The soil photolysis half-lives of mandipropami d were estimated as 16.4–23.9 days (MRID 46800015,16,17).

The linear biodegradation half- life of mandipropamid in six European and one U.S. soils ranged from approximately 26 to 103 days under aerobic conditions (MRIDs 46800020,21,22,24-28).

Based on results form a supplemental study, under anaerobic conditions the rate of biodegradation appears to be much slower. Mandi propamid degraded with linear half-lives of 151 days in a silt loam soil from Switzerland maintained under anaerobic conditions (MRID 48600022).

The aerobic aquatic degradation half-lives of mandipropamid were 17.8-18.5 days in two river water/silt loam sediment systems from England Germany (MRID 46800030-31).

The degradation of one mandipropamid metabolite s was studied in three soils under aerobic conditions, and this metabolite appears to be non-persistent. Based on linear regression analysis, the half-lives of CGA380778 in silt loam soil from Switzer land, a sandy clay loam soil from England, and sandy loam soil from US, were 6.4, 6.9, and 58 days, respectively (MRID# 46800023).

c. Transport and Mobility

Volatilization of mandipropamid from treated fiel ds and water surfaces is not expected to be an important environmental fate process based on a Henry’s Law constant of 8.29x10 -9 atmm 3 /mol, and vapor pressure of 3.52x10 -8 mm Hg (MRID# 46800007, 8).

Mandipropamid is expected to possess moderate mobility in soils based upon K oc values ranging from 405 - 1294, measured in seven so ils from the U.S. and Europe (MRID 46800038-41). Given the range of K oc values in the six so ils tested, mandipropamid possesses the potential to leach into ground water.

The mobility of mandipropamid meta bolites SYN52119, SYN500003, CGA380778, and SYN504851 were also studied. All of thes e metabolites are expected to possess high mobility in soils based upon the submitted data and have the potential to leach into ground water. K oc values of <1 to 31 L/kg were observed in 12 soils (MRID# 46800035, 36, 42-44).27 d. Field Studies

Terrestrial field dissipati on studies (MRID 46800045-47) for ma ndipropamid were studied in four bare plots cropped with field potatoes : in California (sandy loam soil), New York (loamy sand soil), and Georgia (sandy loam soil).

The field dissipation half-lives of mandipr opamid were: 75.3 days (C alifornia site); 100.5 days (New York); 81.5 days (Georgia).

At the California, residues of mandipropamid and CGA380778 were only detected in the top 15 cm of the soil.

At the New York site, residues of mandipropa mid and CGA380778 were only detected in the top 15 cm of the soil.

At the Georgia site, residues of mandipropa mid and CGA380778 were only detected in the top 15 cm of the soil with one exception; ma ndipropamid was detected once in the 15-30 cm depth at 14 days post-treatment.

2. Measures of Exposure

a. Aquatic Exposure Modeling

Exposure concentrations of mandipropamid together with its degradates of concern (SYN500003 and SYN504851) were estimated ba sed on the EFED aquatic Tier I model GENEEC 2.0 (see Appendix B for explanation of model).

The aquatic exposure modeling inputs a nd outputs for mandipropamid including its degradates, SYN500003 and SYN504851, are shown in Tables 6 and 7

.

Table 6. GENEEC Chemical Specific Input Para meters for mandipropamid and its degradate, SYN500003 and SYN504851.

Parameter Input Value and Unit Source Maximum application rate 0.13 lb a.i./A Product Label EPA Reg. No. 100-RELU. Maximum number of applications 4 Product Label EPA Reg. No. 100-RELU. Method of Aerial Product Label EPA Reg. No. 100-RELU.
Minimum interval between applications 7 days Product Label EPA Reg. No. 100-RELU.

Partition coefficient K oc 2.89 mL/g For SYN500003; Lowest non-sand K oc; MRID 46800042,43
Aerobic soil metabolism 72.04 days Total toxic of parent and degradates; MRID 46800021. Input Parameters Guidance, 200228 Table 6. GENEEC Chemical Specific Input Para meters for mandipropamid and its degradate, SYN500003 and SYN504851.

Parameter Input Value and Unit Source Aerobic aquatic metabolism (t 1/2 ) 102 days Total toxic of parent and degradates; MRID 46800030-31. Input Parameters Guidance, 2002 Aquatic photolysis t 1/2 (days) 1.1 For parent; MRID 46800014; input Parameters Guidance, 2002

Table 7. GENEEC2 Model Estimated Envi ronmental Concentrations (EEC) of mandipropamid and its degradates identified as of toxicological concerns, in standard farm pond.

Compound Peak (ppb) 4-day (ppb) 21-day (ppb) 60-day (ppb) 90-day (ppb)

Total Residue including mandipropamid and its degradates, SYN500003 and SYN504851 20.9 20.7 19.4 16.9 15.3

b. Aquatic Exposure Monitoring and Field Data

Since mandipropamid is a new use chemical that has not been registered, no monitoring data exist at this time.

3. Measures of Terrestrial Exposures

a. Terrestrial Exposure Modeling

The EFED terrestrial exposure model T-REX (T -REX, version 1.3.1) is used to estimate exposures and risks to avian and mammalian sp ecies. The model provides estimates of exposure concentrations and risk quotients (R Qs). Specifically, the model provides estimates of concentrations (maximum, or upper bound, and average, or mean) of chemical residues on the surface of different types of foliage and inse cts that may be dietary sources of exposure to terrestrial wildlife receptors.29 T-REX was run for the proposed new uses of mandipropamid using the input values provided in Table 8 . Potential risk from mandipropamid a nd its degradates were addressed by using the default half-life of 35 days which operationa lly results in mandipropamid being relatively stable and is comparable to a total residue a pproach where the degradates are assumed to be as toxic as the parent. The maximum label ra te selected for modeling is the same maximum label rate for all proposed uses.30 Table 8. Input Parameters Used in T-REX Versi on 1.3.1 to Determine Terrestrial EECs for Mandipropamid Application on all proposed uses. Input Variable Parameter Value Source Maximum application rate 0.13 Product label Maximum number of applications per year 4 Product label

Minimum application interval 7 Product label Foliar half-life 35 Default value

Mineau et al . scaling factor 1.15 Default value

Application type Ground Spray or Aerial Spray Product label

Avian
acute oral toxicity No input value because mandipropamid is practically nontoxic to birds on an acute oral basis (No mortalities in acute oral test) 468001-10

Avian
acute dietary toxicity No input value because mandipropamid practically nontoxic to birds on an acute dietary basis (No mortalities in acute dietary test ) 468001-12

Avian reproductive toxicity: NOAEC = 1060 467152-14

Mammalian Acute Oral LD 50 1 No input value because mandipropamid practically nontoxic to mammals on an
acute dietary basis (No mortalities in acute dietary test ) 46800202 Toxicity values

Mammalian Reproductive Toxicity NOAEC = 250 ppm 46800230

A summary of the terrestrial animal estimated exposure concentrations (EECs) in forage generated by T-REX is presented in Table 9 . Mandipropamid residues (ppm) ranged from 631 ppm (fruits/pods/large insects) to 103 ppm (short grass) for maximum residues and 3 ppm (fruits/pods/large insects) to 36 ppm (short grass) for mean residues.

Table 9. Peak Terrestrial EECs Estimated Using Kenaga Values for Mandipropamid Applied to all the proposed uses Forage Type Maximum Residue (ppm) Mean Residue (ppm)

Short grass 103 36 Tall grass 47 15 Broadleaf plants and small insects 58 19 Fruits/pods/large insects 6 3

TerrPlant (TerrPlant, version 1.2.2, dated December 26, 2006) was used to estimate exposures and risks to terrestrial plant species. Input parameters for the model included: (1) toxicity values for monocots and dicots; (2) application rate; (3) runoff, based on chemical solubility; and (4) soil incorporation dept h. The model provides estimates of exposure concentrations and risk quotients (RQs) for non- listed and listed terrestrial and semi-aquatic plants. Input and output values used for estima ting terrestrial and semi -aquatic plant exposure risks to mandipropamid are summarized in Tables 10 and 11, respectively. Only one application is considered in this assessme nt due to model limitations. More detailed information on TerrPlant Version 1.2.2 is presented in Appendix D.

Table 10. Input Parameters Used in TerrPlant 1. 2.2 to Determine Terrestrial EECs for Plants for Mandipropamid Application on all proposed Crops based on the maximum proposed application rate. Input Variable Parameter Value Source Maximum application rate 0.13 lbs a.i./acre Product label Runoff value (0.01, 0.02, or 0.05 if chemical solubility <10, 10–100, or >100 ppm, respectively) 0.02 * MRID 46800009

Minimum incorporation depth (inches) 0 Product label Toxicity Values Most Sensitive Vegetative Vigor Endpoint Values EC 25 >0.792 NOAEC = 0.198 lbs a.i./acre

Most Sensitive Seedling Emergence Endpoint Values EC25 > NOAEC = 0.165 lbs a.i./acre MRID 46695512

a Based on the water solubility of 2.3 ppm.32 Table 11. Summary Output EECS from TerrPlant for Mandipropamid

Application Method EECs for Plants Inhabiting Areas Adjacent to Treatment Site (lbs a.i./acre), Run off & Drift Load EECs for SemiAquatic Plants Inhabiting Areas Adjacent to Treatment Site (lbs a.i./acre), Run off & Drift Load Drift EEC (lbs a.i./acre) Ground spray (unincorporated) 0.0039 0.0273 0.0013

Aerial 0.0091 0.0325 0.0065

b. Terrestrial Residue Studies

No residues studies were submitted for any of the proposed new uses.

C. Ecological Effects Characterization

In screening-level ecological risk assessments, the effects characterization describes the types of effects a pesticide can have on aquatic or te rrestrial organisms. Th is characterization is based on registrant-submitted stud ies that describe informati on regarding acute and chronic toxicity effects of mandipropamid (Technical Grade Active Ingredient (TGAI)) for various aquatic and terrestrial animals. Also included in this charact erization is a limited set of aquatic organism studies test ing the toxicity of the mandi propamid degradate, CGA380778. Appendix E summarizes the results of all regi strant-submitted toxicity studies used to characterize effects for this risk assessment.

1. Aquatic Effects Characterization

The most sensitive freshwater and estuarine/ma rine acute and chronic toxicity values for mandipropamid and its degradate, CGA380778, are summarized in Tables 12 and 13

. Toxicity values typically used by EFED to asse ss a pesticide’s acute risk to fish were not available. This is because all fish acute to xicity studies were deemed invalid. Although aquatic organism results were limited, a Daphnia magna , water flea, acute toxicity test was available for both the parent (48-h 7.1 ppm a.i.) and degradate (48-h 54.2 ppm). As the degradate was less toxic than the parent, the meas ures of toxicity used to evaluate risks to aquatic organisms were based solely on th e parent toxicity data (Table 15).33 Table 12. Mandipropamid Values Used to Ca lculate Screening Level Risks to Aquatic Organisms and Aquatic Plants

Selected Test and Measurement Endpoint Assessment Endpoint (a) Measures of Effect (a) Species Toxicity Value Study Conditions Basis for selection Reference (Classification) 3a. freshwater fish acute 96-hr LC 50 No acceptable studies b -- -- -- --

3c. Freshwater invertebrate acute 96-h LC 50 (for copepods 48-h LC 50 or EC 50 where the effect measured is surrogate) Water flea ( Dapnia
magna ) <24 hours old 48-h EC 50 = 7.1 ppm a.i. (effects: immobility and mortality) TGAI 96.5% a.i., pH range of 7.93-8.07, Temperature range of 20 O + 1 O C Hardness range of 226 mg as CaCO 3 /L Most sensitive (only a single TGAI test) MRID 468000-50 (Acceptable) Survival and reproduction of individuals and communities of freshwater fish and invertebrates in close proximity to sites

3d. Freshwater invertebrate reproductive NOAEC No acceptable studies -- -- -- --

4a. Estuarine or marine fish acute 96-hr LC 50 No acceptable study -- -- -- --

4b. Mollusc acute 96-hr EC 50 shell deposition Eastern oyster ( Crassostrea virginica ) 96-h EC 50 = 0.91 ppm a.i. TGAI 96.1 % a.i., pH range of 8.1- 8.3, Temperature range of 19.1- 19.7 O C, Most sensitive (only a single test result) MRID 468001-01 (Acceptable) Survival and reproduction of individuals and communities of estuarine/marine fish and invertebrates in close proximity to sites

4c. Shrimp acute 96-hr LC 50 Mysid shrimp ( Americamysis bahia ) 96-h LC50 = 1.7 ppm a.i. TGAI 96.1% a.i., pH range of 8.1-8.4, pH 7.5 + 1, Temperature range 23 O C26 O Most sensitive (only a single test result) MRID 468001-02 (Acceptable)34 Table 12. Mandipropamid Values Used to Ca lculate Screening Level Risks to Aquatic Organisms and Aquatic Plants

Selected Test and Measurement Endpoint Assessment Endpoint (a) Measures of Effect (a) Species Toxicity Value Study Conditions Basis for selection Reference (Classification) 4d. Fish early life stage or full life cycle NOAEC Fathead minnow (Pimephales
p romelas ) NOAEC = 0.22 ppm

LOAEC = 0.47 ppm TGAI 96.5% a.i., Hardness range of 38.3-58.0 mg/L as CaCO 3 pH: 7.1-7.9 Temperature range of 24.0-25.5°C Most sensitive endpoint produced in the only fish chronic toxicity test available MRID 468001-08 (Acceptable)

4e. Invertebrate life cycle NOAEC No data submitted -- -- -- --35 Table 12. Mandipropamid Values Used to Ca lculate Screening Level Risks to Aquatic Organisms and Aquatic Plants

Selected Test and Measurement Endpoint Assessment Endpoint (a) Measures of Effect (a) Species Toxicity Value Study Conditions Basis for selection Reference (Classification) 7a. Freshwater green algae, cyanobacteria or diatom 96-h EC 50 for biomass Green algae ( Pseudokirchneriella subcapitata ) 96-h EC 50 >2.5 ppm TGAI 96.5%, static, temperature range of 24 - 25 O C Most sensitive endpoint (Only nonvascular aquatic plant endpoint available) MRID 468001-21 (Acceptable)

7b. Saltwater green algae or diatom 96-h EC 50 for biomass No submitted studies -- -- -- --

7c. Vascular plant (at least duckweed) 7- to 14-d EC 50 for biomass Duck weed ( Lemna Gibba G3 ) 96-h EC 50 > 7.9 ppm TGAI 96.1%, static renewal, p H of 7.5 temperature range of 24.5-24.9 o C, Most sensitive (Only vascular aquatic plant endpoint available) MRID 468001-19 (Acceptable)

7d. Freshwater green algae, cyanobacteria or diatom 96-h NOAEC (or EC 05 ) for biomass Green algae ( Pseudokirchneriella subcapitata ) 96-h EC 50 NOAEC = 1.3 ppm TGAI 96.5%, static, temperature range of 24 - 25 O C Most sensitive endpoint (Only nonvascular aquatic plant endpoint available) MRID 468001-21 (Acceptable) Standing crop or biomass and growth of aquatic plants in close proximity to sites

7e.Vascular plant (at least duckweed) 7- to 14-d NOAEC (or EC 05 ) for biomass Duck weed ( Lemna Gibba G3 ) 96-h IC 05 = 1.3 ppm TGAI 96.1%, static renewal, p H of 7.5 temperature range of 24.5-24.9 o C, Most sensitive (Only vascular aquatic plant endpoint available) MRID 468001-19 (Acceptable)

(a) Assessment endpoints and measures of effect identified to be assessed in the problem formulation (Table 4). (b) Fish acute toxicity is currently unavailable because the submitted fish acute toxicity studies were deemed invalid36 Table 13. Mandipropamid degradate, CGA380778, Aquatic Organism and Aquatic Plant Toxicity Values Test and Measurement Endpoints Assessment Endpoint Measures of Effect Species Toxicity Value Study Conditions Basis for selection Reference (Classification)

3a. Freshwater fish acute 96-hr LC 50 No acceptable study -- -- -- -- Survival and reproduction of individuals and communities of freshwater fish and invertebrates in close proximity to sites 3c. Freshwater invertebrate acute 96-h LC 50 (for copepods 48-h LC 50 or EC 50 where the effect measured is surrogate) Water flea ( Dapnia
magna ) <24 hours old 48-h EC 50 = 54.2 ppm a.i. (effects: immobility and mortality) 98% purity, static, pH range of 7.9- 8.0,Temperature range of 20+1 O C, Hardness of 219 mg as CaCO 3 /L, -- MRID 468000- 51 (Acceptable)

7a. Freshwater green algae, cyanobacteria or diatom 96-h EC 50 for biomass Pseudokirchneriella subcapitata (Freshwater green algae) 96-h EC 50 = 16 ppm a.i. 98% purity, static, pH range 7.4 – 10, Temperature range of 23.8- 24.3 o C -- -- Standing crop or biomass and growth of aquatic plants in close proximity to sites 7d. Freshwater green algae, cyanobacteria or diatom 96-h NOAEC (or EC 05 ) for biomass Pseudokirchneriella subcapitata (Freshwater green algae) 96-h NOAEC = 2.4 ppm -- -- --

a. Aquatic Animals

(1). Acute Effects

Freshwater Fish

At a minimum two freshwater fish acute toxi city studies using the TGAI are required to establish the toxicity of mandipropamid to fish. The preferred test sp ecies are rainbow trout (a coldwater fish) and bluegill sunfish (a warmwater fish). The registrant submitted three freshwater fish toxicity studi es including two studies test ing mandipropamid (TGAI; MRID’s 468001-05, and MRID 468001-06) and one study testing the degradate CGA380778 (MRID 468001-04). All of the studies were deemed inva lid because of significant deviations from the guidelines. The studies were invalid ated because the dissolved mandipropamid concentration was not determined (test soluti ons contained undissolv ed particulate test material and the measured concentrations were significantly unstable throughout the testing).37 Therefore, it is not possible to obtain accurate toxicity endpoint values that could be used for risk assessment purposes.

Freshwater Invertebrates

A freshwater aquatic invertebrate toxicity test using the TGAI is requ ired to establish the toxicity of mandipropamid to aquatic invert ebrates. The preferred test species is Daphnia
magna . Two freshwater invertebrate toxicity studies, one te sting mandipropamid (TGAI), and the other testing the mandipropamid degradate, CGA38077, (MRID’s 468001-50 and 468001-51, respectively) were submitted by the registrant. Both studies were classified as scientifically sound and acceptable for assessing ri sks to freshwater invertebrates; Guideline §72-2 (draft OPPTS 850.1010) is fulfilled. Since the 48-h EC 50 (7.1 ppm a.i.) for mandipropamid falls in the range of 1 - 10 ppm, mandipropamid is classified as moderately toxic to aquatic invertebrates on an acute basis. Since the 48-h EC 50 (54.2 ppm) for the major degradate of mandipropamid, CGA380778 falls in the range of 10 – 100 ppm, CGA380778 is classified as pr actically nontoxic to freshwater invertebrates. The more sensitive value of the parent was selected for us e in assessing risk to freshwater invertebrates (Table 12).

Estuarine/Marine Fish

Mandipropamid usage may occur in some areas as sociated with marine/estuarine habitats. Thus, marine/estuarine fish toxi city data is required (40CFR Part 158) to assess acute risks from mandipropamid use. Two marine/estuari ne fish studies tes ting mandipropamid were submitted by the registrant (MRID 468001-03 and –05). However both studies were reviewed and identified as scientifically uns ound because of significant deviations from the 850 guidelines. The studies were invalidated because test solutions contained undissolved particulate test material, and the mean measur ed concentrations were significantly unstable throughout the test. Hence, no scientifically sound dissolved endpoint value can be determined for these studies. The 40CFR Part 158 acute marine/estuarine fish test requirement (Guideline §72-1, dr aft OPPTS 850.1075) is not fulfilled.

Estuarine/Marine Invertebrates

Mandipropamid usage may occur in some areas as sociated with marine/estuarine habitats. Thus, marine/estuarine inverteb rate toxicity data for a mollu sk (shell deposition or embryolarval test), and shrimp is required (40C FR Part 158) to assess acute risks from mandipropamid use. The registrant submitted tw o marine/estuarine invertebrate toxicity studies testing mandipropam id (MRID’s 468001-02 and 468001-01 ) . One study tested the acute toxic effect of manipropamid on mysid shrimp mortality and the other study tested mandipropamid’s acute toxic eff ects on shell deposition of the eastern oyster. Both tests were reviewed and found to be scientifically sound and acceptable for assessing risk to marine/estuarine invertebrates. The st udies demonstrated that mandipropamid was moderately toxic to mysid shrimp (96-h LC 50 : 1.7 ppm a.i.) and very hi ghly toxic to eastern38 oyster shell deposition (96-h EC 50: 0.91 ppm a.i.). The endpoints produced in these studies will be used to assess the risk of mandipropamid to marine/estuarine invertebrates specifically mollusk and arthropod species ( Table 12 ).

(2). Chronic Effects

Freshwater Fish

Mandipropamid is mobile and is likely to readily and frequently (due to multiple applications during a growing season) reach su rface water bodies. Thus, a fi sh early life stage toxicity study testing mandipropamid is required (40CFR Part 158) to evaluate the potential for reproductive effects. The registrant submitted an early life-stage study testing the technical grade mandipropamid on fathead minnow (MRI D 468001-08). The study was classified as scientifically sound and acceptable for use in as sessing risk. The most sensitive endpoint in this study was on fish growth. The NOAEC for this endpoint was 0.22 ppm a.i.. This endpoint will be used to asse ss the chronic risk of mandipropa mid use to freshwater fish.

Freshwater Invertebrates

Mandipropamid is mobile and is likely to readily and frequently (due to multiple applications during a growing season) reach surface water bod ies. Thus, invertebrate chronic toxicity testing mandipropamid is requir ed (40CFR Part 158) to evalua te chronic effects to use of mandipropamid. The freshwater invertebrate reproductive toxicity study submitted by the registrant (MRID 468001-07) was deemed scientif ically unsound for use in a risk assessment because of significant deviations from the guideli nes for an invertebrate reproductive toxicity test. The reviewer’s analysis showed that reproduction of solven t control daphnids was significantly lower than that of negative control daphnids, which according to the EPA memo titled, “Interim Policy Guidance for the Use of Dilution-Water (Negative) and Solvent Controls in Statistical Data Analysis for Guideline Aqua tic Toxicology Studies”, dated March 30, 2006, would result in the i nvalid classification of this study.

Estuarine/Marine Fish

Currently, no estuarine and marine fish chroni c toxicity studies have been submitted to the Agency.

Estuarine/Marine Invertebrates

Currently, no estuarine and marine invertebrate chronic toxicity studies have been submitted to the Agency.39 (3). Sublethal Effects

Freshwater Fish

All of the acute freshwater fish toxicity studies were reviewed and identified as scientifically unsound (MRID’s 468001-05, 468001-06, and 468001-04). Thus, although sublethal effects (loss of equilibrium, lethargy, surfacing, lying on the bottom of the aquarium) were observed in these studies, the dissolve d concentrations at which thes e occur can not be determined.

The most significant sublethal effects demonstr ated by the freshwater fish chronic toxicity study were adverse effects on fish growth at a NOAEC of 0.210 ppm (MRID 468001-08). Sublethal effects noted in acute studies (los s of equilibrium, lethargy, surfacing, lying on the bottom of the aquarium) were not observed in juveniles in the fish early life stage test.

Freshwater Invertebrates

The only sublethal effects reported for the freshwat er invertebrate toxicity studies were in the study testing the mandipropamid degradate, CGA380778. The study reported the test organism ( daphnia magna ) having slow and/or lethargi c movement during the test termination at 4.6 – 65 ppm (MRID’s 468001-51).

Estuarine/Marine Fish

All of the acute marine/estuarine fish toxic ity studies were reviewed and identified as scientifically unsound (MRID 468001-03 and –05). Thus, although sublethal effects (erratic swimming, loss of equilibrium, lying on the bottom of test vessel, lethargy) were observed in these studies, the dissolved concentrations at which these occur cannot be determined.

Estuarine/Marine Invertebrates

Except for the effect on shell deposition no other sublethal effects were reported in the shell deposition or mysid shrimp st udies (MRID’s 468001-02, and 468001-01).

(4). Field Studies

No aquatic field studies for mandipropamid were submitted.

Plants Inhabiting Aquatic Areas

The registrant has submitted a nonvascular aquatic plant toxicity study testing the effect of mandipropamid on the green alga, Pseudokirchneriella subcapitata (MRID 468001-21) and a vascular aquatic plant toxicity study te sting the effect of mandipropamid on Lemna gibba (MRID 468001-19). Both studies of these studies are acceptable for aquatic plant toxicity requirements. The green algal study demonstrated an EC 50 > 2.5 ppm a.i. for all endpoints40 measured and a NOAEC of 1.3 ppm based on biomass. The Lemna gibba study demonstrated an EC 50 > 7.9 ppm a.i. for all endpoints measured and a NOAEC of 1.3 based on growth rate. These endpoints will be used to assess the risk of mandipropamid to aquatic nonvascular and vascular plants respectively.

The registrant has also submitted a nonvascular a quatic plant toxicity study testing the effect of CGA380778, a mandipropamid degradate, on Pseudokirchneriella subcapitata (MRID 468001-20). This study was reviewed and identi fied as a scientifically sound and an acceptable study for estimating risks to aquatic plants. The EC 50 and NOAEC values produced in the study were 16 ppm and 2.4 pp m respectively. Since the aquatic plant toxicity studies testing the parent, mandipropamid, demonstrated a more sensitive NOAEC values than the study testing CGA380778 (a NOAEC of 1.3 ppm for the parent vs. a NOAEC of 2.4 for CGA380778), the risk to aquatic plants will be assessed solely based on the parent toxicity data.

2. Terrestrial Effects Characterization

The most sensitive acute and chronic toxicity values associated with mandipropamid exposure to mammals, birds, and terre strial plants are summarized in Table 14. These values are used to assess risk to terres trial animals. All toxi city endpoint values utilized to assess the potential terrestrial risks of mandipropamid exposure were obtained from studies testing the technical grade mandipropamid. Except for an earthworm acute toxicity study testing, CGA380778, no other terrestrial or ganism toxicity tests were available testing any of the mandipropamid formulated products or mandipropa mid degradates or metabolites. A more detailed summary of all available terrestrial toxicity data used to characterize effects associated with mandipropamid is given in Appendix E.41 Table 14. Mandipropamid Selected Toxicity Values for Screening Risk to Terrestrial Organisms

Selected Test and Measurement Endpoints Assessment Endpoint Measures of Effect Species Toxicity Value Study Conditions Basis for Selection Reference (Classification) 1a. Avian (single dose) acute oral LD 50 Mallard duck LD 50 >1000mg a.i./kgbw (a) (no mortality observed) TGAI, 96.5% a.i., Single dose, 18weeks of age Lowest value of the two species tested MRID 468001-10 (Acceptable)

1b. Avian subacute 5-day dietary LC 50 Mallard duck and Bobwhite quail 5-d LC 50 > 6080 mg a.i./kg diet (a) (no mortality observed) TGAI, 96.5% a.i., 8-d test, 5-d exposure in food, 10 days old Both available studies were of equal sensitivity MRID 468001-12 (Acceptable) MRID 468001-13 (Acceptable) Abundance (i.e., survival, reproduction, and growth) of individuals and populations of birds in close proximity to sites

1c. Avian reproduction NOAEL Mallard duck and Bobwhite quail NOAEC > 1060 mg a.i./kg diet (c) TGAI, 20-week avian reproduction study, exposed via food Both available studies were of equal sensitivity MRID 468001-14 (Acceptable) MRID 468001-15 (Acceptable) 2a. Mammalian acute oral (single dose) LD 50 No data -- -- -- -- Abundance (i.e., survival, reproduction, and growth) of individuals and populations of mammals in close proximity to sites 2b. Mammalian reproductive NOAEC or NOAEL Laboratory Rat ( Rattus norvegicus ) NOAEC = 250 ppm a.i. (a) (based on most sensitive endpoints: decreased body weights, weight gains, food consumption, and food utilization) TGAI, Twogeneration, exposure via food Most sensitive study (only study available) MRID 46800230 (Acceptable)

Survival of beneficial insect populations in close proximity to sites Honey bee
acute contact LD 50 Honey bee ( Apis mellifera L.) 72-h LC 50 >200 ug a.i./bee TGAI, applied to Most sensitive (only study available) 468001-16 (Acceptable)42 Table 14. Mandipropamid Selected Toxicity Values for Screening Risk to Terrestrial Organisms

Selected Test and Measurement Endpoints Assessment Endpoint Measures of Effect Species Toxicity Value Study Conditions Basis for Selection Reference (Classification) 6a. Monocot seedling
emergence EC 25 All monocot species tested including corn, oat, onion,
ryegrass >0.660 lbs a.i./A Mandipropamid Formulation A12496B All four
monocots tested

were equally sensitive 468001-17 (Acceptable)

Dicot seedling
emergence EC 25 All dicot species tested except for carrot which produced unreliable results. The other tested dicot species included cucumber, radish, soybean, sugar beet, and tomato >0.660 lbs a.i./A Manipropamid formulation A12496B Most sensitive of the validated endpoint of the dicots tested 468001-17 (Supplemental)

6b. Monocot seedling
emergence NOAEC corn, oat, onion, and
ryegrass 0.660 lbs a.i./A Mandipropamid formulation A12496B All four
monocots tested

were equally sensitive 468001-17 (Acceptable)

Dicot seedling
emergence NOAEC cucumber, and soybean 0.165 lbs a.i./A Mandipropamid formulation A12496B Most sensitive validated endpoint of the dicots tested. 468001-17 (Supplemental)

6c. Monocot vegetative vigor EC 25 corn, oat, onion,
ryegrass >0.792 lbs a.i./A Mandipropamid formulation A12496B All four
monocots tested

were equally sensitive 468001-18 (Acceptable) Survival and growth of terrestrial plants in close proximity to sites

Dicot vegetative vigor EC 25 carrot, cucumber, radish, soybean, sugar beet,
tomato >0.792 lbs a.i./A Mandipropamid formulation A12496B All six dicots tested

were equally sensitive 468001-18 (Acceptable)43 Table 14. Mandipropamid Selected Toxicity Values for Screening Risk to Terrestrial Organisms

Selected Test and Measurement Endpoints Assessment Endpoint Measures of Effect Species Toxicity Value Study Conditions Basis for Selection Reference (Classification) 6d. Monocot vegetative vigor NOAEC oat 0.198 lb a.i./A Mandipropamid formulation A12946B Most sensitive of the four
monocots tested 468001-18 (Acceptable)

Dicot vegetative vigor NOAEC Carrot, cucumber, radish, soybean, sugar beet,
tomato 0.792 lb a.i./A Mandipropamid formulation A12946B All six species tested

were equally sensitive 468001-18 (Acceptable)

(a) Note: Since, acute toxicity studies in birds demonstrated acute toxicity (LC 50 or LD 50 ) values higher than the highest concentrations tested and resulted in no mortalitie s, acute risk quotients will not be derived for birds.

a. Terrestrial Animals

(1). Acute Effects

Birds

An acute oral toxicity study and two subacute dietary studies using the technical grade of the active ingredient (TGAI) are requi red (40CFR Part 158) to esta blish the acute toxicity of mandipropamid to birds. The preferred test sp ecies are a waterfowl (Mallard duck) and an upland gamebird (Northern bobwhite quail). Two studies were submitted by the registrant evaluating the acute oral toxicity and acute dietary toxicity of th e technical grade of mandipropamid on Bobwhite quail and the Mallard duck (MRID’s 468001-10, 468001-11, 468001-12, and 468001-13, respectively). All four studi es were reviewed and identified to be scientifically sound and classified as accepta ble for use in assessi ng risks to birds. No mortalities were observed in acute oral expos ures to mandipropamid at up to 1000 mg a.i./kgbw (highest concentration test ed) for the Mallard duck and at up to 2250 mg a.i./kg-bw for the Northern bobwhite quail or in acute di etary exposure to mandipropamid at up to 6080 ppm a.i. for both species. Thus, mandipropamid is classified as practically nontoxic to avian species on an acute basis.44 Mammals

Wild mammal testing is required on a case-by-ca se basis, depending on the results of lower tier laboratory mammalian studies, intended use pattern and pertinent environmental fate characteristics. In most cases, rat or mouse toxicity values obtained from the Agency's Health Effects Division (HED) substitute for wild mammal testing. The registrant has submitted one acute oral mammalian toxicity study testing mandipropamid toxicity on rats (MRID 46800202). The study demonstrated ma ndipropamid is practically nontoxic to mammals (LD 50 > 5000 mg/kg).

Terrestrial Invertebrates

A honey bee acute contact study using the TGAI is required for mandipropamid because its proposed uses may result in honey bee exposur e. An acceptable 72-hour contact toxicity study of technical grade mandipropa mid in honey bees yielded a LD 50 >200 μg a.i./bee (MRID 468001-16), indicating that technical gr ade mandipropamid is practically non-toxic to honey bees. This value was used to screen for risks to terrestrial beneficial insects.

A scientifically sound earthworm acute to xicity study testing the technical grade mandipropamid (MRID 468001-22) and an earthwo rm acute toxicity study testing the mandipropamid degradate, CGA380778, (MRID 468001- 23) were submitted to the Agency. No earthworm mortality was observed in either study the highest concentration tested was 1000 mg a.i./kg of soil.

(2). Chronic Effects

Birds

There were two registrant submitted avian repr oductive toxicity studies testing technical grade mandipropamid. The test organisms in th ese studies were Bobw hite quail and Mallard duck. Both studies demonstrated that mandipr opamid did not cause an y significant effects on reproduction or growth and survival of chic ks at 1060 ppm a.i. which was the highest concentration tested. This value was used to screen for chronic reproductive risks.

Mammals

There is one registrant submitted rat multigen erational reproductive toxicity study (MRID 468002-30). The results of the study demons trated a parental systemic NOAEL and offspring NOAEL of 250 ppm a.i. based on decreased parental body weights, decreased parental weight gains, decreased parental food consumption, decreased parental food utilization, decreased pup body weights in both sexes a nd delayed sexual maturation in offspring. The NOAEL of 250 ppm a.i. produced in this study will be used to assess the chronic risk of mandipropamid to mammals.45 Terrestrial Invertebrates

No chronic toxicity study was submitte d for technical grade mandipropamid, its formulations, or degradates fo r terrestrial invertebrates.

(3). Sublethal Effects

Birds

In the acute oral toxicity study testing the acute oral effect of technical grade mandipropamid on bobwhite quail study, the only subl ethal effects were the appearance of ruffled feathers on one bird in the control group and in five bird s from the 2250 mg a.i./kg bw group. All birds appeared normal in appearance after 4 hours of dosing. Although the ruffled appearance may have been due to stress caused by handling du ring dosing, a treatment -related effect could not be precluded (MRID 468001-10). No simila r sublethal effects were observed in the dietary study with bobwhite quail (MRID 468001-13) or in the acute oral toxicity and dietary studies with Mallard ducks (M RID 468001-11 and –12, respectively).

In the acute oral toxicity study testing mandipropamid on the Mallard duck the only sublethal effects were four females in the 1000 mg a. i./kg-bw group observed drinking frequently during the first 2 hours following dosing. No bird s, however, from this level were observed to regurgitate. In the 1500 mg a.i./kg-bw group, one female and two males were observed drinking frequently, almost imme diately following dosing. Both females that were observed drinking frequently were obser ved regurgitating approximately 30 minutes following dosing. One male was also observed regurgitating ap proximately 1 hour and 20 minutes following dosing. All birds were normal in appearan ce and behavior by 3.5 hours following dosing. Based on regurgitation, the NOAEL for clinical si gns of toxicity was 1000 mg a.i./kg-bw (MRID 468001-11)

. Both acute dietary studies demonstrated visually determined treatment related decrease in body at the highest concentration tested which was 6080 ppm a.i. (MRID’s 468001-12 and 468001-13).

Mammals

Based on the available mammalian toxicity data, the only sublet hal effects of mandipropamid to mammals was demonstrated in the ra t multigenerational study (MRID 46800230). The sublethal effects demonstrated in this study we re decreased parental body weights, decreased parental weight gains, decreased parental food consumption, decreased parental food utilization, decreased pup body weights in both sexes a nd delayed sexual maturation in offspring. The NOAEL of these effects were 250 ppm a.i..46 Terrestrial Invertebrates

The only terrestrial invertebrate studies which demonstrated any sublet hal effects were the mandipropamid and CGA380778 earthworm t oxicity studies (MRID’s 468001-22 and 468001-23). The sublethal effects in the studies included significant reductions in percent weight loss which were demonstrated at a NOAEC of 320 mg/kg of soil and a LOAEC of 1000 mg/kg of soil for the study testing mandi propamid and at a NOAEC of 100 mg/kg of soil and a LOAEC 1000 mg/kg of so il for the study testing CGA380778.

(4). Field Studies

No field studies were submitted for mandipropamid or any of its degradates.

b. Terrestrial Plants

The registrant submitted a seedling emergence and vegetative vigor study testing the A12946B, the formulation containing the active ingredie nt Mandipropamid. The following summarizes the results of both studies.

The effect of A12946B on the seed ling emergence of monocot (corn, Zea mays ; oat, Avena sativa ; onion, Allium cepa ; and ryegrass, Lolium perenne ) and dicot (carrot, Daucus carota ; cucumber, Cucumis sativa ; radish, Raphanus sativus ; soybean, Glycine max ; sugar beet, Beta vulgaris ; and tomato, Lycopersicon esculentum ) crops was studied at nominal application rates of 0 (negative and surfact ant controls), 0.0413, 0.0825, 0.165, 0.330 and 0.660 lbs a.i./A. The growth medium used in the seedling emergence test was natural soil, classified as a loam soil, with an organic matter content of 1.7% (1.0% or ganic carbon) and an adjusted pH of 7.4. On day 21 the surviving plants per po t were recorded and cut at so il level for measuring the plant height and dry weight.

Dry weight was significantly a ffected in cucumber, soybean and tomato, but reductions did not exceed 25%. The percent inhibition in seedling emer gence in the treated species as compared to the control ranged from -4 to 8%. No monocot species were sensitive to treatment, but an EC 05 value could be calculated for corn dry weight. Carrot was the only dicot species to exhibit a reduction of ≥ 25% (based on dry weight) re lative to the negative cont rol; however, the response was not dose-dependent, with the three lowest treatment groups experiencing increases in dry weight of 2-21%. The reviewer was unable to determine reliable EC x values for carrot dry weight. Additionally, one replicate in the highe st treatment group failed to emerge and overall emergence of the controls and treatment groups was fairly low (60-73%). This implies that factors other than treatment contributed to the poor performance of carro t in this study. The study was deemed supplemental because of this study deficiency.

The effect of A12946B on the vege tative vigor of monocot (corn, Zea mays ; oat, Avena sativa ; onion, Allium cepa ; and ryegrass, Lolium perenne ) and dicot (carrot, Daucus carota ; cucumber, Cucumis sativa ; radish, Raphanus sativus ; soybean, Glycine max ; sugar beet, Beta vulgaris ; and tomato, Lycopersicon esculentum ) crops was studied at nominal a pplication rates of 0 (negative47 and surfactant controls), 0.0495, 0.0994, 0.198, 0.396 and 0.792 lbs a.i./A. The growth medium used in the test was an artificial soil that repr esented a loam soil and was composed of a mixture of kaolinite clay, industrial quartz sand and peat; the organi c matter content was 1.7% (1.0% organic carbon) and the pH was 7.4. On day 21 th e surviving plants per pot were recorded and cut at soil level for measuring th e plant height and dry weight.

In the vegetative vigor test, plant height was affected by A12946B treatment in oat only. Dry weight, plant height and survival were not aff ected in any other species. The most sensitive monocot species, based on plant height, in th e vegetative vigor test was oat with an EC 25 of >0.792 lbs a.i./A and a NOAEC of 0.198 lbs a.i./A. No dicot was sensitive to treatment, so the EC 25 value was >0.792 lbs a.i./A and the NOAEC values was 0.792 lbs a.i./A (the highest concentration tested).

The study was deemed acceptable for a Tier II vegetative vigor terrestria l plant toxicity study.48 IV. RISK CHARACTERIZATION

Risk characterization is the integration of e xposure and effects characterization to determine the ecological risk from the use of mandipr opamid and the likelihood of effects on aquatic life and wildlife based on all the proposed uses at the ma ximum proposed use rate. The risk characterization provides estimati on and description of the risk; articulates risk assessment assumptions, limitations, and uncertainties; synthe sizes an overall conclusion; and provides the risk managers with informati on to make regulatory decisions.

A. Risk Estimation – Integration of Exposure and Effects Data

Results of the exposure and toxi city effects data are used to evaluate the likelihood of adverse ecological effects on non- target species. For the asse ssment of mandipropamid risks, the risk quotient (RQ) method is used to co mpare exposure and measur ed toxicity values. Estimated environmental concentrations (EECs) for acute and chronic exposure are divided by acute and chronic toxicity values, respectivel y. The resulting RQs are then compared to the Agency’s levels of concern (LOCs). The LOCs, as summarized in the Risk Characterization Section, are the Agency’s inte rpretive policy used to analyze potential risk to non-target organisms and the n eed to consider regulatory action.

1. Non-Target Aquatic Animals and Plants

To assess risks of mandipropamid on all proposed uses to non-target aquatic organisms (i.e., fish, invertebrates, plants), surface water EEC s for total residues of mandipropamid including its degradates of toxic concern, SYN500003 and SYN504851 (as iden tified by HED), were obtained using GENEEC based on the maximum pr oposed label rate of 4 applications, 7 days apart at 0.13 lbs a.i./A. The instaneous p eak concentration is us ed to derive RQs for acute exposure and the 21-day a nd 60-day peak exposure concentra tions were used to derive RQ values for chronic exposure to invertebra tes and fish, respectively. The most sensitive toxicity values for the TGAI mandipropamid were used to calculate risk quotients for aquatic organisms exposed to mandipropamid.

a. Acute Risk to Animals (Fish and Invertebrates)

Only acute RQ values for freshwater and mari ne/estuarine invertebra tes were calculated. According to the acute RQ values for aquati c invertebrates, mandipropamid does not pose a risk to freshwater or marine/estuarine inve rtebrates above the Agency’s Level of Concern (see Table 15 ). Acute RQ values could not be calcul ated for freshwater and marine/estuarine fish because all the acute fish t oxicity data were deemed invalid.49 Table 15. Acute RQs for Aquatic Or ganisms Exposed to Mandipropamid including its degradate of toxic concern, SYN500003 and SYN504851.

Measure of Effect(Test Species) Toxicity Value (ppm) EEC Peak (ppm) Acute RQ (EEC/Toxicity Value) Freshwater Invertebrates (Test Species: Water flea) 48-h EC 50 7.l 0.021 0.003 *

Marine/Estuarine Invertebrates (Test Species: Mysid Shrimp) 96-h LC 50 1.7 0.021 0.01 *

Marine/Estuarine Invertebrates (Test Species: Eastern Oyster) 96-h EC 50 0.91 0.021 0.02 *

* Does not exceed acute endangered species LOC of 0.05 or acute LOC of 0.1

b. Chronic Risk to Aquatic An imals (Fish and Invertebrates)

Only a chronic RQ for freshwater fish fr om exposure to mandipropamid was calculated. Chronic RQ values for estuarine and marine fish and invertebrates and freshwater invertebrates from exposure to mandipropamid c ould not be calculated because either the submitted data were invalid or no study was subm itted. Based on the freshwater fish chronic RQ value, mandipropamid does not pose a chronic risk to fish (Table 16).

Table 16. Chronic RQs for Aquatic Or ganisms Exposed to Mandipropamid

Chemical Measure of Effect (Test Species) NOAEC (ppm) 60 day EEC value (ppm) Chronic RQ (EEC/NOAEC) Mandipropamid Freshwater fish (Test Species: Fathead minnow) 0.210 0.0095 0.05 *

* Does not exceed chronic LOC of 1.50 c. Risks to Aquatic Plants

Based on the RQ calculations for aquatic plan ts, mandipropamid usage is not expected to exceed the Agency’s Level of Concer n for risk to aquatic plants ( Table 17 ).

Table 17. Risk Quotients for Aquatic Plants Algae Exposed to the Mandipropamid

Type of aquatic plant Organism 4-d EC 50 (ppm) 4-d NOAEC (ppm) EEC Peak (ppm) RQ Non-Listed (EEC/EC 50 ) RQ Listed (EEC/NOAEC) Aquatic vascular plant Duck weed ( Lemna gibba ) > 7.9 1.3 0.021 < 1 0.02*

Aquatic nonvascular plant >2.5
ppm 1.3 0.021 < 1 0.02*

* Does not exceeds endangered or non-endangered species LOC (1)

2. Non-Target Terrestrial Animals

To assess risks of mandipropamid to non-target terrestrial animals, EECs and acute and chronic RQs for residues on various forage cate gories (short grass, tall grass, broadleaf plants/small insects, fruits/pods/l arge insects, and seeds) were obtained from the Tier I model T-REX for maximum proposed application rates. An explanation of the model is presented in Appendix C.

a. Acute Risk to Mammals and Birds

Acute RQ values for avian or mammalian speci es were not calculated because the highest concentration or dosages tested in the acute dietary test (6080 ppm) and acute oral test (>1000 mg/kg-bw) for both a Mallard duck and Northe rn bobwhite and the acute oral test for mammals (> 5000 mg/kg) did not resu lt in any mortality (MRID 468001-10, 468001-11, 468001-12, and 468001-13). Therefore at the highe st dietary residue level (103 ppm) no mortality from mandipropamid is likely gi ven that no mortality was observed at concentrations 60 times above this residue level in laboratory birds and mammals.

b. Chronic Risk to Birds and Mammals

Dietary-based chronic RQs for bird s and mammals are summarized in Table 18 . Chronic RQs for birds and mammals are below the chroni c LOC (1) for all dietary residue categories.51 Table 18. Dietary-Based Chronic RQs for Bird s and Mammals Based on Upper Bound Residues as Calculated by T-REX

Avian Chronic Risk Quotients Based on Chronic NOAEC of 1060 ppm. Crop Use Short Grass Tall Grass Broadleaf Plants/Small Insects Fruits/Pods/ Large Insects All proposed crops (See Usage Overview Section 4.) 0.10* 0.04* 0.05* 0.01*
* Note: Does not exceed the chronic LOC (1) for terrestrial animals.

Mammalian Chronic Risk Quotients Based on a Chronic NOAEC of 250 ppm. Crop Use

Short Grass Tall Grass Broadleaf Plants/Small Insects Fruits/Pods/ Large Insects All proposed crops (See Usage Overview Section 4.) 0.41* 0.19* 0.23* 0.03*
* Note: Does not exceed the chronic LOC (1) for terrestrial animals

c. Risk to Terrestrial Invertebrates

Although EFED does not quantitatively assess risk s to non-target terres trial invertebrates, acute toxicity studies show th at mandipropamid TGAI is prac tically non-toxic to honey bees and nontoxic to earthworms at the highest dose te sted. Additionally, acute toxicity studies on the mandipropamid degradate, CGA380778, demons trated that CGA380778 is nontoxic to earthworms at the highest dose tested.

3. Non-target Plants Inhabiting T errestrial and Semi-Aquatic Areas

RQs were not calculated to determine mandipropa mid’s risk to nontarget nonlisted terrestrial plant species because for all the plant species tested in the vegetative vigor study and seedling emergence study the validated EC 25 values were above the highest levels tested. These test levels were above the highest propos ed use rates. Thus, EFED does not expect mandipropamid to pose a significant risk to nonlisted terrestrial plants. Table 19 demonstrates the listed terrestrial plant RQs for mandipropamid based on the NOAEC values demonstrated in the terrestrial plant studies . The RQs indicate that mandipropamid does not pose a risk to listed terrestri al plants that exceeds the Agency’s Level of Concern.52 Table 19. Risk Quotients for Non-Listed Species and Listed Species Terrestrial and Semi-Aquatic Plant Emergence in Areas Adjacent to Treatmen t Sites (due to drift) for Mandipropamid Risk Quotients b
Terrestrial Plant Emergence (Adjacent Area) Semi-Aquatic Plant Emergence (Adjacent Area) Terrestrial Plant Vegetative Vigor (Drift) Application Rate (lbs a.i./acre) Crop Use Monocot Dicot Monocot Dicot Monocot Dicot Listed Terrestrial and Semi-Aquatic Plant 0.14 All proposed uses at the maximum application
rate 0.006 c 0.02 c 0.04 c 0.17 c 0.0001 c 0.0001 c

a RQs are calculated using TerrPlant. See Appe ndix D for explanation TerrPlant model.
b Based on the NOAEC values = 0.165 lb a.i./acre and 0.660 lb a.i./acre for seedling emergence study in dicots and monocots respectively and NOAEC = 0.792 for vege tative vigor in monocots and dicots.

c Does not Exceed Listed Species LOC for Terrestrial and Semi-Aquatic Plants ( ≥ 1)

B. Risk Description

1. Risks to Aquatic Organisms

Based on risk estimates, the proposed mandipr opamid uses are not expected to pose a significant

• acute risk to freshwater or ma rine and estuarine invertebrates

• acute risk to aquatic plants

• chronic risk to freshwater fish.

These conclusions are based on the premise that the RQ values for acute risk to aquatic invertebrate, acute risk to plants, and chronic risk to fish are severa l orders of magnitude below the Agency LOC. Currently, EFED is unable to definitively determine whether mandipropamid poses an acute risk to fish b ecause of the lack of acceptable fish acute toxicity data.

2. Risks to Terrestrial Organisms

a. Terrestrial Animals (Mammals and Birds)

Based on available registrant submitted data, mandipropamid is not expected to pose a significant chronic or acute risk to birds or mammals.

EFED avian and mammal acute and chronic risk conclusions are based on the fact that the acute toxicity studies in birds and mammals failed to establish acute lethality values, with no mortalities at the highest doses/concentrations tested and the RQs for chronic risk to birds53 were several orders of magnitude lower than the Agency Level of Concern for avian chronic risk.

EFED’s conclusion regarding th e chronic mammalian risk is based on the premise that the chronic RQ values (derived from the rat multigenerational NOAEC of 250 ppm based on decreases in body weight, weight gains, food consumption, and food utilization) were more than 2 times less than the LOC for chronic dietary risk. Thus, EFED does not expect mammalian chronic exposure to mandi propamid to be a significant risk.

b. Insects

Although EFED does not derive RQ values for non-target insects, risks can be assessed qualitatively. Results of toxi city studies on technical grade mandipropamid show that the compound is practically non-toxic to honey bees on both a contact and an oral basis and non toxic to earthworms at the highest concentratio ns tested (1000 mg/kg in soil). Therefore, acute risks of technical grade mandipropamid e xposure to pollinators and other beneficial insects are not anticipated.

c. Plants

Formulated Product

EFED does not expect mandipropamid to pose a signi ficant risk to terrestrial plants. This determination is based on the premise that the RQ values for plants are several orders of magnitude lower than the Agency LOC.

There is some uncertainty regarding the plant emergence RQ values because they are based on a supplemental seedling emergence study. The study was deemed supplemental because the carrot species tested did not yield any reliable endpoint va lues. EFED assessed the plant emergence risk of mandipropamid based on th e other 9 species te sted (all of which demonstrated no significant ri sk from mandipropamid that exceeded the Agency LOC). Thus, there is some uncertainty whether plan t species closely related to carrots may be adversely affected by mandipropamid, since EFED had no reliable test data on carrots.

3. Review of Incident Data

Incident reports submitted to EPA since approximately 1994 have been tracked by assignment of EIIS (Environmental Incident Info rmation System) in an Incident Data System (IDS). Since mandipropamid is a new chemical a nd has not been previously approved for use in the U.S., there are no incident reports.

4. Endocrine Effects

None of the available data i ndicate that mandipropamid may ha ve detrimental effects on the endocrine system.54 C. Federally Threatened and Enda ngered (Listed) Species Concerns

1. Action Area

For listed species assessment pur poses, the action area is consider ed to be the area affected directly or indirectly by the Federal action and not merely th e immediate area involved in the action. At the initial screeni ng level, the risk assessment considers broadly described taxonomic groups and so conservatively assume s that listed species within those broad groups are collocated 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 to the treated site. The assessment also assumes that the listed species are located within an assumed area which has the relatively highest potential exposu re to the pesticide, and that exposures are likely to decrease with distance from the treatment area. Th is risk assessment presents the use of mandipropamid on all proposed uses including brassica, leafy greens, bulb vegetables, cucurbits, grapes, leafy vegetables, peppers, and other fruiting vegeta bles and establishes initial collocation of species with treatment areas.

If the assumptions associated with the screening level assessment result in RQs that are below the listed species LOCs, a "no effect" de termination conclusion is made with respect to listed species in that taxa, and no furthe r refinement of the action area is necessary. Furthermore, RQs below the listed species LOCs for a given taxonomic group indicate no concern for indirect effects upon listed sp ecies 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 gi ven taxonomic group, a potential for a "may affect" conclusion exists and may be a ssociated with direct effects on listed species belonging to that taxonomic group or may extend to indirect effects upon listed species 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, and the locations of use sites could be considered to determine the extent to which screening assumptions regarding an action area apply to a particular listed organism. These s ubsequent refinement steps could consider how this information would impact the action area for a particular listed organism and may potentially include areas of exposure that are downwind and downstream of the pesticide use site.

2. Taxonomic Groups Potentially at Risk

This screening level risk assessment indicates that uses of mandipropamid will have: 1) no direct or indirect acute risk to listed aquatic invertebra tes, 2) no direct or indirect chronic risk to fish, 3) no direct or indirect acute or chronic risk to birds, 3) no dire ct or indirect acute or chronic risk to mammals, and no direct risk to aquatic plan ts. Currently, EFED cannot definitively determine the acute risk to fish, or chronic risk to aquatic invertebrate because of the lack of acceptable toxicity data for these organisms.55 The Agency has developed the Endangered Species Protection Program to identify pesticides whose use may cause adverse impacts on enda ngered and threatened species, and to implement mitigation measures that address these impacts. The Endangered Species Act (ESA) requires federal agencies to ensure that their actions are not likely to jeopardize listed species or adversely modify designated critical habitat. To analyze the potential of registered pesticide uses that may affect any particular species, EPA uses basic toxicity and exposure data and considers it in relation to individua l species and their locations by evaluating important ecological parameters, pesticide us e information, geographic relationship between specific pesticide uses and species locations, and biological requirements and behavioral aspects of the particular species , as part of a refined use and species-specific analysis. When conducted, this species-specific analysis will ta ke into consideration any regulatory changes that have been implemented at that time.

3. Probit Dose Response Relationship

Because there were no LOC exceedances for any organisms based on any of the available data a Probit Analysis was not warranted.

4. Indirect Effects Analysis

Because there were no LOC exceedances for any organisms based on any of the available data an indirect effects analysis was not warranted.

5. Critical Habitat

In the evaluation of pesticide e ffects on designated critical habita t, consideration is given to the physical and biological feat ures (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 re quire special management considerations or protection. The evaluation of imp acts for a screening level pesticide risk assessment focuses on the biological features that are constituent elements and is accomplished using the screening level taxonomic analysis (RQs) and listed species’ leve ls of concern (LOCs) that are used to evaluate direct and in direct effects to listed organisms.

Because there were no LOC exceedances for any organisms based on any of the available data an identification of any endangered species critical habitat was not warranted.56 D. Description of Assumptions, Limitati ons, Uncertainties, Strengths and Data Gaps

1. Assumptions, Limitations, Uncertainties, Strengths and Data Gaps Related to Exposure for All Taxa

There are a number of areas of uncertainty in the aquatic and terrestrial risk assessments. The toxicity assessment for terrestrial and aquati c animals is limited by the number of species tested in the available toxicity studies. Use of toxicity data on representative species does not provide information on the potential variability in susceptibility to acute and chronic
exposures.
This screening level risk assessment relies on labeled statements of the maximum rate of mandipropamid application, the maximum number of applications, and the shortest interval between applications. Together, these assumpti ons constitute a maximum use scenario. The frequency at which actual uses approach these maximums is dependant on resistance to the fungicide, timing of applicat ions, and market forces.

2. Assumptions, Limitations, Uncertainties, Strengths and Data Gaps Related to Exposure for Aquatic Species

a. GENEEC 2.0 Model

GENEEC is a single event model. It assumes one single large rainfall/runoff event occurs that removes a large quantity of pesticide from the field to the water all at one time. Longerterm, multiple-day average concentration values are calculated based on the peak day value and subsequent values considering degradati on processes. This computer-based model utilizes basic chemical parameters (solubility, photolysis, hydrolysis, K oc , and soil degradation) combined with a pplication rate and method of so il incorporation to determine the EEC. The model considers the reduction in di ssolved pesticide residues due to adsorption to soil or sediment, incorporation dept h, degradation in soil before washoff to a water body, and degradation of the residues within the water body. The model assumes that the runoff from a 10 hectare (24.7 acre) field is entering a 1 hectare (2.47 acre) by 2 meter (6.56 feet) deep pond. GENEEC is a more extensive mathematical model designed from output generated by the PRZM and EXAM models. Howe ver GENEEC is a generic, in that it does not consider differences in climate, soil, topography, or crop in estimating pesticide exposure. GENEEC is used as a tool to specif ically estimate a pesticide concentration in a standard water body due to off-ta rget movement of pesticide. This model has been used by OPP primarily in the first-tier risk assessm ent of pesticide expos ure to aquatic life.

OPP uses computer modeling (GENEEC) to estima te pesticide concentrations in an edge-ofthe-field pond for use in screening ecological exposure and risk assessments. Such modeling has also been used as a screen for drinking water assessments (http://www.epa.gov/oscpmont/sap/mee tings/1997/december/finaldec.pdf).57 3. Assumptions, Limitations, Uncertainties, Strengths and Data Gaps Related to Exposure for Terrestrial Species

a. Residue Concentration

The data available to support the exposure assessment for mandipropamid is substantially complete, with the exception of a foliar dissipation study, which is an input variable for Tier I modeling of risks to birds and mammals (i.e ., T-REX Model). The terrestrial modeling was conducted with a default foliar ha lf-life of 35 days, which may not be realistic, however, is likely a conservative foliar half-life for this compound.

b. Variation in Habitat and Dietary Requirements

For screening terrestria l risk assessments, a generic bird or mammal is assumed to occupy either the treated field or adjacent areas receiv ing pesticide at a rate commensurate with the treatment rate on the field. The habitat and f eeding requirements of the modeled species and the wildlife species may be different. It is assumed that species occupy, exclusively and permanently, the treated area being modeled. Th is assumption leads to a maximum level of exposure in the risk assessment.

The acute studies have a fixe d exposure period, not allowing for the differences in response of individuals to different durations of exposure. Further, for the acute oral study, mandipropamid is administered in a single dose which does not mimic wild birds’ exposure through multiple feedings. Also, it does not accoun t for the effect of different environmental matrices on the absorption rate of the chemi cal into the animal. Because exposure occurs over several days, both the accumulated dose and elimination of the chemical from the body for the duration of the exposure determine the exact exposure to wildlife, however, they are not taken into account in the sc reening assessment. There was also no assumption of an effect of repeated doses that change the tolera nce of an individual to successive doses.

c. Variation in Diet Composition

The risk assessment and calculated RQs assume 100% of the diet is rele gated to single food types foraged only from treated fields. The a ssumption of 100% diet from a single food type may be realistic for acute exposures, but diets are likely to be more variable over longer periods of time. This assumption is likely to be conservative and will tend to overestimate potential risks for chronic exposure, especially for larger organisms that have larger home ranges. These large animals (e.g., deer and geese) will tend to forage from a variety of areas and move on and off of treated fields. Small animals (e.g., mice, voles, and small birds) may have home ranges smaller than the size of a treated field and will have li ttle or no opportunity to obtain foodstuffs that have not been treate d with mandipropamid. Even if their home range does cover area outside the trea ted field, mandipropamid may have drifted or runoff to areas adjacent to the treated field.58 d. Exposure Routes Other than Dietary

Screening level risk assessments for spray a pplications of pesticid es consider dietary exposure to terrestrial organisms. Other exposur e routes are possible for animals residing in or moving through treated areas. These routes include ingestion of contaminated drinking water, ingestion of contaminated soils, preening/grooming, and dermal contact. Preening exposures, involving the or al ingestion of material from th e feathers remains an unquantified, but potentially important, exposure route. If toxi city is expected through any of these other routes of exposure, then the risks of a toxic response to mandipropamid is underestimated in this risk assessment. Other routes of exposur e, not considered in this assessment, are discussed below.

e. Incidental Soil Ingestion Exposure

This risk assessment does not consider incident al soil ingestion. Available data suggests that up to 15% of the diet can consist of incident ally ingested soil depending on the species and feeding strategy (Beyer et al. 1994). Alt hough mandipropamid it is not expected to be persistent in soils, incidental ingestion of soil within days of mandipropamid application may be an important exposure pathway.

f. Inhalation Exposure

The screening risk assessment does not consider inhalation exposure, due to the low volatility of mandipropamid; it is not expected to be an important exposure pathway.

g. Dermal Exposure

The screening assessment does not consider de rmal exposure. Dermal exposure may occur through three potential sources: (1 ) direct application of spray to terrestrial wildlife in the treated area or within the drift footprint; (2) in cidental contact with c ontaminated vegetation; or (3) contact with contaminated water or soil.

The available measured data related to wildlife dermal contact with pesticides are extremely limited. The Agency is actively pursuing modeling techniques to account for dermal exposure via direct application of spray and by incidental contact with vegetation.

h. Drinking Water Exposure

Drinking water exposure to a pesticide active ingr edient may be the result of consumption of surface water or consumption of the pesticide in dew or other water on the surfaces of treated vegetation. Given that mandipropami d has a high solubility in wate r, there is the potential for mandipropamid to dissolve in runoff and puddl es on the treated field. Consumption of drinking water would appear to be inconsequentia l if water concentrations were equivalent to the concentrations from PRZM/EXAMS; however , concentrations in puddled water sources on treated fields may be higher than concentr ations estimated in the 1 ha pond used in EXAMS. Given that this exposure route is no t included in the assessment, overall risk may59 be underestimated. Although the potential imp act of discharging groundwater is not explicitly delineated, it should be noted that groundwater could provide a source of pesticide to surface water bodies – especially low-orde r streams, headwaters, and groundwater-fed pools. This is particularly likely if the chemi cal is persistent and m obile. Soluble chemicals that are only subject to photolytic degradation will be very likely to persist in groundwater, and can be transportable over long distances. Much of this groundwater will eventually be discharged to the surface – often supporting stream flow in the absence of rainfall. Continuously flowing low-order streams in particular are su stained by groundwater discharge, which constitutes 100% of stream flow during baseflow (no runoff) conditions. Thus, it is important to keep in mind that pesticides in groundwater can have a major (detrimental) impact on surface water quality.

i. Dietary Intake – Differences Between Laboratory and Field Conditions

Several aspects of the dietary test introdu ce uncertainty into calculation of the LC 50 value (Mineau et al. 1994; ECOFRAM 1999). The end point of this test is reported as the concentration mixed with food that produces a response rather than as the dose ingested. Although food consumption sometimes allows for the estimate of a dose, calculations of the mg/kg/day dose are confounded by undocumented sp illage of feed and how consumption is measured over the duration of the test. Usuall y, if measured at all, food consumption is estimated once at the end of the five-day e xposure period. Furthemore, for studies in avian, group housing of birds undergoing testing only allows for a measure of the average consumption per day for a group; consumption estimates can be further confounded if birds die within a treatment group. Th e exponential growth of young birds also 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 in itiation of the exposure period and at the end, the dose per body weight (mg/kg) is difficult to estimate with any precision. The interp retation of this test is also confounded because the response of bi rds is not only a function of the intrinsic toxicity of the pesticide, but also the w illingness of the birds to consume treated food.

Further, the acute and chronic characterization of risk rely on comparisons of wildlife dietary residues with LC 50 or NOAEC values expressed in concentr ations of pesticides in laboratory feed. These comparisons assume that ingestion of food items in the field occurs at rates commensurate with those in the laboratory. Although the screening assessment process adjusts dry-weight estimates of food intake to reflect the increased mass in fresh-weight wildlife food intake estimates, it does not allow for gross energy and assimilative efficiency differences between wildlife food items and la boratory feed. On gross energy content alone, direct comparison of a laborator y dietary concentration based effects threshold to a freshweight pesticide residue estimate would resu lt in an underestimati on of field exposure by food consumption by a factor of 1.25–2.5 for mo st food items. Only for seeds would the direct comparison of dietary threshold to residue estimate lead to an overestimate of
exposure.60 Differences in assimilative efficiency between laboratory and wild diet s suggest that current screening assessment methods do not account fo r a potentially important aspect of food requirements. Depending upon species and dietar y matrix, bird assimilation of wild diet energy ranges from 23–80%, and mammal's a ssimilation ranges from 41–85% (USEPA 1993). If it is assumed that labora tory chow is formulated to maximize assimilative efficiency (e.g., a value of 85%), a potential for underes timation of exposure may exist by assuming that consumption of food in the wild is co mparable with consump tion during laboratory testing. In the screening process, exposure may be underestimated because metabolic rates are not related to food consumption.

Finally, the screening procedur e 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 specific wildlife scenario s (e.g., bird migration) where the food intake rate may be greatly increased. Kirkwood (1983) has suggested that an upperbound limit to this behavior might be the typical intake rate multiplied by a factor of 5. In contrast is the potential for avoidance, ope rationally defined as animals responding to the presence of noxious chemicals in their food by reducing consumption of treated dietary elements. This response is seen in natu re where herbivores avoid plant secondary compounds.

In the absence of additional information, the acute oral LD 50 test provides th e best estimate of acute effects for chemicals where exposure can be considered to occur over relative short feeding periods, such as the diurnal feedi ng peaks common to avian species (ECOFRAM 1999).

4. Assumptions, Limitations, Uncertainties, Strengths and Data Gaps Related to Effects Assessment

a. Age Class and Sensitivity of Effects Thresholds

It is generally recognized that test orga nism age may have a significant impact on the observed sensitivity to a toxicant. The screening risk assessment acute toxicity data for fish are collected on juvenile fish between 0.1 and 5 grams. Aquatic invertebrate acute testing is performed on recommended immature age cla sses (e.g., first instar for daphnids, second instar for amphipods, stoneflies, and mayflies, and third instar for mi dges). Similarly, acute dietary testing with birds is also performed on juveniles, with mallard ducks being 5–10 days old and bobwhite quail 10–14 days old.

Testing of juveniles may overest imate toxicity of older age classes for pesticidal active ingredients, such as mandipropamid, that ac t directly (without metabolic transformation) because younger age classes may not have the enzymatic systems associated with detoxifying xenobiotics. The screening risk assessment ha s no current provisions for a generally applied method that accounts for this uncertainty. In so fa r as the available toxicity data may provide ranges of sensitivity information with respect to age class, the risk assessment uses the most sensitive life-stage information as the conservative screening endpoint.61 b. Use of the Most Sensitive Species Tested

Although the screening risk asse ssment relies on a sele cted toxicity endpoint from the most sensitive species tested, it doe s not necessarily mean that th e selected toxicity endpoint reflects sensitivity of the most sensitive species existing in a given environment. The relative position of the most sensitive species tested in the distribution of all possible species is a function of the overall variability in sensitivity among species to a particular chemical. In the case of listed species, there is uncertainty regarding the rela tionship of the listed species' sensitivity and the most sensitive species tested.

The Agency is not limited to a base set of surr ogate toxicity information in establishing risk assessment conclusions. When available, the Ag ency also considers toxicity data on nonstandard test species.62 

### V. REFERENCES

Open Literature, Government Reports, and Product Labels

Beyer, W.N. 1994. Estimates of soil inges tion by wildlife. J Wild l Manage 58(2):375–382.

Davis, G.E., P.L. Haaker, and D.V. Richards. 199 6. Status and trends of white abalone at the California Channel Islands. Transactions of the American Fisheries Society 125:42–48.

Fletcher, J.S., J.E. Nellesson, and T. G. Pfl eeger. 1994. Literature revi ew and evaluation of the EPA food-chain (Kenaga) nomogram, an in strument for estimating pesticide residues on plants. Environ Toxicol Chem 13(9):1383–1391.

Kirkwood JK. 1983. Minireview. A limit to metabolisable energy inta ke in mammals and birds. Comp Biochem Physiol A 75(1):1-3.

Martin, C. M., H. S. Zim, and A. C. Nels on. 1951. American Wildlife and Plants - A Guide to Wildlife Food Habits, Dover Publishers Inc., New York.

Mineau, P., B.T. Collins, and A. Baril. 1996. On the use of scaling factors to improve interspecies extrapolation to acute toxicity in birds. Reg Toxicol Pharmacol 24:24–29.

Urban, D.J. and Cook, N. 1986. Hazard Evaluation Division, Standard Ev aluation Procedure: Ecological Risk Assessment 104.pp. Document Number No. PB 86 247 657. EPA-540/9-86- 167.

USDA. 2002. 2002 Census of Agriculture. Available on-line at http://www.nass.usda.gov/Cens us_of_Agriculture/index.asp

U.S. EPA. 1993. Wildlife Exposure Factors Handbook. Volume I of II. EPA/600/R-93/187a. U.S. Environmental Protection Agency, Office of Research and Development, Washington, DC. 20460.

U.S. EPA. 1999. ECOFRAM. U.S. Environm ental Protection Agency, Washington, DC. Available on-line at http://www.epa.gov/oppefed1/ecorisk/index.htm

. U.S. EPA. 2001. Ecological Risk Assessor Or ientation Package. U.S. Environmental Protection Agency, Ecological Fate and E ffects Division. Draft Version, August 2001.

U.S. EPA. 2002a. Data Requirements for Re gistration. U.S. Environmental Protection Agency, Washington, DC. Code of Federal Regulations 40 CFR §158.202.

U.S. EPA. 2002b. Guidance for Selecting Input Parameters in Modeling the Environmental Fate and Transport of Pesticides, Version II. U.S. Environmental Protection Agency, Washington, DC. February 28, 2002.63 U.S. EPA. 2004. Overview of Ecological Risk Assessment Process in the Office of Pesticide Programs, U.S. Environmental Protection Ag ency. Endangered and Threatened Species Effects Determinations. Office of Prevention, Pesticides, and Toxic Substances, Office of Pesticides Programs. Washington, DC. January 23, 2004.

U.S. EPA. 2006a. User’s Guide for T-REX (Terrestrial Residue E xposure model) Version 1.3.1 U.S. Environmental Protection Agency. Release December 7, 2006.

U.S. EPA. 2006b. TerrPlant Terrestrial Pl ant Exposure Model. Version 1.2.2. U.S. Environmental Protection Agenc y. Released December 26, 2006.64 

# APPENDIX A. Environmental Fate Data

161-1. Hydrolysis

MRID 46800007,8 (Acceptable)

[ethyl-1- 14 C]-labeled 2-(4-chlorophenyl)-N-[2-(3 -methoxy-4-prop-2-ynyloxy-phenyl)-ethyl]- 2-prop-2-ynyloxy-acetamide (mandipropamid; NOA446510; radiochemical purity 98.9%) was stable in pH 5, 7, and 9 sterile aqueous bu ffered solutions at 25 oC over the course of a 32-day incubation period. Ov erall recoveries of [ 14 C]residues averaged 100.0 ± 3.4% of the applied (range 94.4-104.9%) from the pH 5 buffer solution, 98.1 ± 0.8% of the applied (range 97.2-99.4%) from the pH 7 buffer solution, and 100.1 ± 1.1% (range 99.1-101.6%) from the pH 9 buffer solution. There was no pattern of lo ss of material over time from any of the buffer solutions. [ 14 C]Mandipropamid averaged 97.8-102.5% of the applied in the pH 5 solutions, 97.5-99.0% in the pH 7 solutions, and 99.3-101.6% in the pH 9 solutions. No major or minor transformation products we re detected; mandipropamid was the only compound detected and comprised 100% of the rec overed at all sampling intervals. Volatiles were not measured. This study is classified as Acceptable.

161-2. Aqueous Photolysis

MRID 46800009 (Acceptable)

[chlorophenyl-U- 14 C]-labeled 2-(4-chlorophenyl )-N-[2-(3-methoxy-4-prop-2-ynyloxyphenyl)-ethyl]-2-prop-2-ynyloxy-acetamide (mandipropamid; NOA446510; radiochemical purity > 98%), at a nominal concentration of 1 μ g a.i./mL, at 25 ° C in sterilized pond water from the UK (pH 7.02), degraded with a reviewe r-calculated first-order linear half-life of 15.2 hours based on the continuous irradiation of 44.79 W/m 2 (300-400 nm); 1 hour of artificial light was equi valent to 0.65 hours of summer sunlight (68.98 W/m 2 ; 300-400 nm) at 40 ° N latitude. Mandipropamid was stable in the dark controls dur ing the 7 days of incubation. In the irradiated buffer soluti ons, no major transformation products were identified. Polar compounds totaled a maximu m average of 36.7% of the applied at 168 hours posttreatment (individual sample s 24.7% and 48.7%). Two minor nonpolar transformation products were identified. CGA380778 and NOA458422 averaged maximums of 3.7% and 3.9% of the applied, respectively. The study is Acceptable.

MRID 46800010 (Acceptable)

[methoxyphenyl-U- 14 C]-labeled 2-(4-chl orophenyl)-N-[2-(3-m ethoxy-4-prop-2-ynyloxyphenyl)-ethyl]-2-prop-2-ynyloxy-acetamide (mandipropamid; NOA446510; radiochemical purity > 95.7%), at a nominal concentration of 1 μ g a.i./mL, at 25 ° C in sterilized pond water from the UK (pH 7.02). degraded with a reviewe r-calculated first-order linear half-life of65 15.2 hours based on the continuous irradiation of 22.4 hours, continuously irradiated using a filtered xenon lamp (300- 800 nm) for 166.4 hours ( ca. 7 days). Mandipropamid was stable in the dark control during the 3 days of incubation. No majo r transformation products were isolated and no minor transforma tion products were identified in either the irradiated samples or dark controls. In the irradiated solu tions only, unidentified pol ar compounds totaled a maximum of 25.0% of the applied at 72.2 hours pos ttreatment. This fraction consisted of at least 14 separate components with no single component > 8.4% of the applied. At 72 hours posttreatment, 14 CO 2 averaged 6.0% of the applied in th e irradiated samples and were not detected in the dark controls. Based on the study results, mandipropamid photodegrades to numerous minor polar compounds and CO 2 . The study is Acceptable.

MRID 46800011,12 (supplemental)

[chlorophenyl-U- 14 C]-labeled 2-(4-chloro-phenyl )-N-[2-(3-methoxy- 4-prop-2-ynyloxyphenyl)-ethyl]-2-prop-2-ynyloxy-acetamide (m andipropamid; NOA446510) radiochemical purity 98.1%), at a nominal concen tration of 1.0 mg a.i./L at 25 ° C sterile pH 7 buffer (0.01M phosphate), continuously irradiat ed using a filtered xenon lamp (290- 750 nm) for 15 days, dissipated with a half-life of 6.6 days (158.4 hour s), based on the conti nuous irradiation of 30.74 W/m 2 (300-400 nm); 1 hour of artificial light wa s equivalent to 0.45 hours of summer sunlight (68.98 W/m 2 ; 300-400 nm) at 40 ° N latitude. [ 14 C]Mandipropamid was stable in the dark controls. No major transformation products were isolated from either the irradiated samples or dark controls. Based on the study results, mandipropamid photodegrades to numerous minor transformation products and CO 2 . This study is supplemental and upgradeable upon submission of the detailed results (concentrati on of parent) or the square vessel experiment.

MRID 46800013,14 (Acceptable)

[methoxyphenyl-U- 14 C]-labeled 2-(4-chloro-phenyl )-N-[2-(3-methoxy-4-prop-2-ynyloxyphenyl)-ethyl]-2-prop-2-ynyloxy-acetamide (mandipropamid; NOA446510; radiochemical purity > 99%), at a nominal concentra tion of 1.0 mg a.i./L, at 25 ° C sterile pH 7 buffer (0.01M phosphate) continuously irradiat ed using a filtered xenon lamp (300- 800 nm) for 336 hours, dissipated with a half-life of 26.4 hours, base d on the continuous irradiation of 29.93 W/m 2 (300-400 nm); 1 hour of artificial light was equivalent to 93 W/m 2 (300-400 nm); 1 hour of artificial light was equi valent to 0.43 hours of summer sunlight (68.98 W/m 2 ; 300-400 nm) at 40 ° N latitude. No major transfor mation products were isolated from either the irradiated samples or dark controls. No minor transforma tion products were identif ied in the irradiated samples and none were isolated from the dark controls. In the irradiated buffer solution, 16 minor nonpolar transformati on products, none averaging > 5% of the applied, and at least 10 minor polar transformation products were isolated.66 161-3. Soil Photolysis

MRID 46800015 (Acceptable)

[ 14 C-chlorophenyl]-labeled 2-(4-chlorophenyl)- N -[2-(3-methoxy-4-prop-2-ynyloxy-phenyl)- ethyl]-2-prop-2-ynyloxy-acetamide (mandi propamid; NOA446510; radiochemical purity

> 98.0%) on loam soil (pH 7.1, organic matter 3.5 %) from Switzerland under continuous irradiation for 15 days at 20 ± 2 ° C, degraded with a half-life of 16.39 days and 20.33 days in the irradiated samples for the dry soil and mois t soil experiments, respectively. The intensity of the Xenon arc lamp was 53.14-53.98 W/m 2 /nm, which was reported to be similar to natural summer sunlight at latitude 30-50 ° N. Mandipropamid de grades to CGA380778, NOA458442 and SYN521195. CGA380778 degrad es to NOA459119 and CGA380775. NOA458442 degrades to CGA380775 a nd SYN505503. SYN521195 degrades to SYN505503. CGA380775 degrades to NOA459 119. The transformation products are ultimately degraded to non-extractable residue s and carbon dioxide. This study is acceptable.

162-1. Aerobic Soil Metabolism

MRID 46800020,21 (Acceptable)

[ 14 C-chlorophenyl]-labeled 2-(4-chlorophenyl )-N-[2-(3-methoxy-4-prop-2-ynyloxy-phenyl)- ethyl]-2-prop-2-ynyloxy-acetamide (mandi propamid; NOA446510; radiochemical purity 99.28%) was applied at the rate of 0.23 mg a.i./k g soil, equivalent to 150 g a.i./ha (nominal) to a sandy loam soil (pH 6.6, organic carbon 0.5% ) from Visalia, California for 371 days under aerobic conditions in darkness at 25 ± 1 ° C and 75% field moisture capacity at 1/3 bar. The linear and nonlinea r half-lives of [ 14 C]mandipropamid in aerobic soil were 72.2 and 34.3 days, respectively. No major transformati on products were identi fied. Four minor transformation products identified: CGA 380778 (benzeneacetamide, 4-chloro-alphahydroxy-N-[2-[3-methoxy-4-(2-p ropynyloxy)phenyl]ethyl]) was a maximum of 4.25% at 30 days, CGA380775 (benzeneacetamide, 4-ch loro-alpha-hydroxy-N-[2-(4-hydroxy-3- methoxyphenyl)ethyl]) was a maximum of 0.5 1% at 30 days, SYN500003 was a maximum of 0.27% at 7 days, and NOA458422 was a maximum 0.18% at study termination.

A supplementary study at a high dose was conduc ted in order to identify mandipropamid and transformation products. Mandipropamid was app lied to soil at 1.35 mg a.i./ kg soil. The concentration of mandipropamid decreased from 97.25% of the applied at day 0 to 48.74% at 59 days and was 6.69% at study termination. The first-order linear a nd nonlinear half-life values were 100.5 and 59.2 days, respectivel y, in the sandy loam soil. The major transformation product was volatilized 14 CO 2 totaling 43.1% of the applied. Four minor transformation products were iden tified as CGA380778, CGA380775, SYN500003 and NOA458422.67 A second supplementary study was performed to de termine the microbial viability of the soil by monitoring for carbon dioxide efflux with a Micro-Oxymax Biomass Analyzer for ca . 18 hours. The biomass of the soil samples af ter incubation for 0, 182 and 371 days was 124.07, 62.32 and 44.43 mg C/kg soil, respectiv ely. This study is acceptable.

MRID 46800022 (Supplemental)

[methoxyphenyl-U- 14 C]-labeled 2-(4-chl orophenyl)-N-[2-(3-m ethoxy-4-prop-2-ynyloxyphenyl)-ethyl]-2-prop-2-ynyloxy-acetamide (mandipropamid, NOA 446510; radiochemical purity 98.9%} was studied in a silt loam soil (pH 7.2, organic carbon 2.14%) from Switzerland for 120 days under aero bic conditions in dark at 20.3 ± 0.3 ° C and 40% of water holding capacity at pF 1. [ 14 C]Mandipropamid was applied at th e rate of 0.40 mg a.i./kg soil, which is equivalent to 0.30 kg a.i./ha. Based on nonlinear analysis and using individual sample data, the half-life was determined to be 19.6 days. The first-or der linear half-life was 26.1 days.

No major transformation products were isolate d. The only minor transformation product that was identified was CGA380778 which averaged a maximum of 2.9% of the applied. Unidentified “Minor metabolites” (up to 13 compounds) totaled a maximum of 2.4%, and “remainder” (unresolved radioactivity in HP LC and Soxhlet extracts) was observed at a maximum of 8.7%. Extractable [ 14 C] residues decreased from 96.79% of the applied at time 0 to 9.07% at 120 days, while nonextractable [ 14 C]residues increased to 45.45% at 120 days. At 120 days posttreatment, 14 CO 2 and organic volatiles accounted for 37.06% and 0.01% of the applied, respectively. This study is classified as suppl emental and upgradeable upon submission of additional information related to cl assification of soils us ed in this study, in accordance to FAO Soil Classification (i.e. Soil Units) or equivalent U.S. Soil Taxonomy.

MRID 46800023 (Supplemental)

The biotransformation of [ 14 C-methoxyphenyl]-labeled 2-(4-c hloro-phenyl)-2 -hydroxy-N-[2- (3-methoxy-4-prop-2-ynyloxy-pheny l)-ethyl]-acetamide (CGA380778; radiochemical purity 97.9%) was studied in a silt loam soil (pH 7.35, organic carbon 2.2%) from Switzerland and a sandy clay loam soil (pH 5.88, organic carbon 2.7%) from the United Kingdom for 28 days and a sandy loam soil (pH 6.0, organic carbon 0. 5%) from the United States for 120 days under aerobic conditions in darkness at 19.3 ± 0.5 ° C and soil moisture of pF2. [ 14 C]CGA380778 was applied at a rate of 0.09 mg a.i. /kg, equivalent to 9 g a.i./ha (nominal). CGA380778 dissipated more slowly in the sandy loam soil compared to the silt loam and sandy clay loam soils. The linear and nonlin ear half-lives of C GA380778 were 6.4 and 3.5 days in the silt loam soil, 6.9 and 3.1 days in the sandy clay loam soil and 57.8 and 41.5 days in the sandy loam soil, respectively. One ma jor transformation product was volatilized 14 CO 2 (identification confirmed) to taling means of 51.0%, 50.6% and 31.5% of the applied for the silt loam, sandy clay loam and sandy loam soils, respectively, at study termination; volatile68 [ 14 C]organic compounds were not detected ( ≤ 0.2%) for all three soils at any sampling interval. No minor transformation products were identified. This study is classified as supplemental and upgradeable upon submission additional information related to classifi cation of soils used in this study, in accordance to FAO Soil Classification (i.e. Soil Units) or equivalent U.S. Soil Taxonomy.

MRID 46800024,25 (Supplemental)

The biotransformation of [ 14 C-methoxyphenyl]-labeled 2-(4 -chlorophenyl)-N-[2-(3-methoxy4-prop-2-ynyloxy-phenyl)-et hyl]-2-prop-2-ynyloxy-aceta mide (mandipropamid; NOA446510; radiochemical purity > 97%) was studied in a sandy loam soil (pH 7.3, organic carbon 2.3%) from Switzerland for 119 days unde r aerobic conditions in darkness at 20 ± 2 ° C and 75% of pF2 moisture. Mandipropamid was applied at the rate of 0.2 mg a.i./kg soil and 1.0 mg a.i./kg soil (nominal). At the 0.2 mg a.i./kg application rate, the linear and nonlinear half-lives of mandipropamid were 77.9 and 77.0 days, respectively. Two minor transformation products, CGA380778 and SYN5 36638 (unknown 1) formed at maximums of 1.4% (28 and 119 days) and 2.4% (91 days) of th e applied, respectively. One transformation product, NOA458422, was detected by LC/MS/MS, but was below the limit of detection for HPLC. At study termination volatilized 14 CO 2 totaled 21.8% of the applied. At the 1.0 mg a.i./kg application rate, the li near and nonlinear half- lives of mandipropamid were 103.5 days. Two minor transfor mation products, CGA380778 and SYN536638 (unknown 1) formed at maximums of 1.7% (7 days) and 3.1% (119 days) of the applied, respectively. Total extractable [ 14 C]residues decreased from an average of 94.4% of the applied at day 0 to 49.2% at study termination, while nonextractable [ 14 C]residues increased from 1.3% of the applied at day 0 to 27.1% at study termination. At study termination, volatilized 14 CO 2 totaled 19.7% of the applied.

Mandipropamid is ultimately degraded into carbon dioxide and unextractable residues. Two supplementary studies were performed w ith soil samples treated with 0.2 mg a.i./kg mandipropamid maintained at low moisture (30% of pF2 moisture) and at low temperature (10 ° C) for 119 days. Mandipropamid degraded more slowly in the supplementary experiments. In the low moisture study, the concentration of mandipropamid decreased from an average of 92.6% of the applied at day 0 to 53.7% at study termin ation. The calculated DT50 and DT90 were 149.5 and 497.2 days, respec tively, based on both simple first-order regression, and first-order multi-compartment regression. The same transformation products, CGA380778 and SYN536638 (unknown 1), we re detected in each study at ≤ 1.7% of the applied.

This study is classified as supplemental a nd upgradeable upon the submission of additional information related to classifi cation of soils used in this study, in accordance to FAO Soil Classification (i.e. Soil Units) or equivalent U.S. Soil Taxonomy.69 MRID 46800027 (Supplemental)

The biotransformation of [chlorophenyl-U- 14 C]-labeled 2-(4-Chl orophenyl)-N-[2-(3- methoxy-4-prop-2-ynyloxy-phenyl)-ethyl]-2-p rop-2-ynyloxy-acetamide (mandipropamid, NOA446510, radiochemical purity 100%} was studi ed in a loam/silt loam soil (pH (KCl) 7.3, organic carbon 1.7%) from Switzerland for 120 days under aerobic conditions in dark at 19.0 ± 0.6 ° C and soil moisture content of 100% of pF 2. [ 14 C]Mandipropamid was applied at the rate of 0.40 mg a.i./kg soil, which is equivalent to 0.30 kg a.i./ha. The nonlinear analysis (SigmaPlot v 9) and using individual sample data, the half-life was determined to be 26.1 days. The first-order linear ha lf-life was 32.4 days. No majo r transformation products were isolated. The only minor transformation pr oduct that was identified was CGA380778, which averaged a maximum of 3.2% of the applied. Nine minor transformation products totaled a maximum of 2.4% of the applied and “remainder” (unresolved radioactivity) was observed at a maximum of 11.4%. At 120 days posttreatment, [ 14 C]CO 2 and organic volatiles accounted for 36.0% and 0.0% of the applied, respectively.

Based on the study results, mandipropamid degrades into multiple minor metabolites, including CGA380778, CO 2 , and tightly bound residues.

This study is classified as as supplemen tal and upgradeable u pon the submission of additional information related to classification of soils used in this study, in accordance to FAO Soil Classification (i.e. Soil Units ) or equivalent U.S. Soil Taxonomy.

MRID 46800028 (Supplemental)

The biotransformation of [ 14 -C-chlorophenyl]-labeled 2-(4 -chlorophenyl)-N-[2-(3-methoxy4-prop-2-ynyloxy-phenyl)-et hyl]-2-prop-2-ynyloxy-aceta mide (mandipropamid; NOA446510; radiochemical purity > 98.7%) was studied in a sa ndy clay loam soil (pH 6.2, organic carbon 3.5%) from the United Kingdom, a loamy sand soil (pH 6.5, organic carbon 0.8%) from Germany and a loam soil (pH 8.5, organic carbon 1.3%) from France for 120 days under aerobic conditions in darkness at 20 ± 2 ° C and pF2 moisture. Mandipropamid was applied at the rate of 0.2 mg a.i./kg soil (nominal).

In sandy clay loam soil, based on first-orde r linear and nonlinear regression analysis, mandipropamid degraded with half-life values of 51.3 and 43.9 days, respectively. In loamy sand soil, based on first-order linear and nonlinear regression analysis, mandipropamid degraded with half-life values of 83.5 and 80.6 days, respectively. In loam soil, based on first-order linear and In sandy clay loam soil, based on first-order linear (Excel 2003) and nonlinear (SigmaPlot v 9) regression analysis, mandipropamid degraded with half-life values of 51.3 and 43.9 days, respectively (DER Attachment 2). Observed DT50 value was 21-28 days (Table 9, p. 51). Using Model Manager v. 1.1, the study author determined the half-life for mandi propamid using simple first order and first70 order multicompartment kinetics as 43.9 and 33.7 days, respectively (p. 26, Table 8, p. 50, Appendix 7, p. 40 and Figure 29-30, pp. 116-117).

In loamy sand soil, based on first-order linear and nonlinear regression analysis, mandipropamid degraded with half-life values of 83.5 and 80.6 days, respectively. In loam soil , based on first-order linear and nonlin ear regression analysis, mandipropamid degraded with half-life values of 90.0 and 85.6 da ys, respectively. In each of the soils, one minor transformation product was identified as CGA380778. LC/MS/MS analysis identified low levels of transformation products not identified by HPLC and 2D-TLC including: CGA380775, NOA458422 and SYN505503. Mandipropami d is ultimately degraded into carbon dioxide and bound residues. This study is classified as as supplemental and upgradeable upon the submission of additional information related to classification of soils used in this study, in accordance to FAO Soil Cl assification (i.e. Soil Units) or equivalent U.S. Soil Taxonomy.

162-2 Anaerobic Soil Metabolism

MRID 46800027 (Supplemental)

The biotransformation of [chlorophenyl-U- 14 C]-labeled 2-(4-chl orophenyl)-N-[2-(3- methoxy-4-prop-2-ynyloxy-phenyl)-ethyl]-2-p rop-2-ynyloxy-acetamide (mandipropamid, NOA446510, radiochemical purity 100%} was studi ed in flooded loam/silt loam soil (pH (KCl) 7.3, organic carbon 1.7%) from Switzerland for 120 days under anaerobic conditions in dark at 19.0 ± 0.6 ° C. [ 14 C]Mandipropamid was applied at the rate of 0.40 mg a.i./kg soil, which is equivalent to 0.30 kg a.i./ha. An aerobicity, temperature and other experimental conditions were reportedly mainta ined throughout the study. In the water layer, the dissolved oxygen and pH levels were 0.01-0.96 mg/L a nd 6.50-8.77, respectively. Redox potentials in the water layer ranged from

− 148 to + 68 mV; redox potentials in the soil ranged

− 232 to + 72 mV. The viability of the soil microflora in soil treated with mandipropamid was not determined.

Based on first-order linear regr ession analysis, mandipropamid di ssipated with a half-life of 198.0 days. Based on nonlinear analysis, the half-life was 183 days.

No major transformation products were isolate d. The only minor transformation product that was identified was CGA380778, which averaged a maximum of 3.9% of the applied. Nine minor transformation products totaled a maximum of 4.1% of the applied and “remainder” (unresolved radioactivity) was observed at a maximum of 9.6%. At 120 days postflooding, the nonextractable residues were partitioned into 3.1-6.5% of th e applied as fulvic acids, 1.3- 5.6% humic acids and 16.7-25.2% hu min. At 120 days postflooding, 14 CO 2 and organic volatiles accounted for 17.4% and 0.2%, resp ectively. Based on the study results, mandipropamid degrades into multiple minor metabolites, including CGA380778, CO 2 , and tightly bound residues. This study is classified as suppl emental and upgradeable upon the submission of additional information related to cl assification of soils us ed in this study, in accordance to FAO Soil Classification (i.e. Soil Units) or equivalent U.S. Soil Taxonomy.71 162-3 Anaerobic Aquatic Metabolism

MRID 46800033,34 (Unacceptable)

The biotransformation of [methoxyphenyl-U- 14 C]-labeled 2-(4-chloro-phenyl)-N-[2-(3- methoxy-4-prop-2-ynyloxy-phenyl)-ethyl]-2-p rop-2-ynyloxy-acetamide (mandipropamid, NOA446510; radiochemical purity ≥ 98.0%) was studied in lake water-silt loam sediment (water pH 8.1-8.25, dissolved organic carbon 12.1 mg/L; sediment pH 7.2-7.6, organic carbon 5.5%) and lake water-loamy sand sedime nt (water pH 5.8-5.83, dissolved organic carbon 1.5 mg/L; sediment pH 4.6-5.3, organi c carbon 0.9%) systems from the United Kingdom for 120 days under anaerobic conditions in darkness at 20 ± 2 ° C. Based on the water volume, [ 14 C]mandipropamid was applied at a rate of 0.26 mg a.i./L. For both systems, the sediment:water ratio used wa s 1:4 (40 g dry wt. sediment:160 g water). The test conditions presented in the study appe ar to have been maintained throughout the 120-day incubations. In untreated lake wate r-silt loam systems incubated alongside the treated systems, conditions were moderately reducing to moderately oxidizing in the water layers and moderately reducing in the se diment with average redox potentials of + 253 ± 79 mV and + 124 ± 15 mV, respectively, and water pH levels of 8.24 ± 0.15. In untreated lake water-loamy sand systems, conditions in th e water layers and se diment went from moderately reducing during the initial month posttreatment to moderately oxidizing from 2 months to study termination with average redox potentials in the water layer and sediment increasing from + 78 ± 14 mV at 6 days posttreatment to + 231 ± 10 mV at 59 days and were

+ 229 ± 7 mV at 119 days; water pH levels averaged 7.51 ± 0.33 over the 120-day incubation.

For both systems, the following four tr ansformation products were detected:

• 2-(4-chloro-phenyl)-N-[2-(3-hydroxy-4 -prop-2-ynyloxy-phenyl )-ethyl]-2-prop-2- ynyloxy-acetamide (SYN521195),

• N-[2-(4-allyloxy-3-hydroxy- phenyl)-ethyl]-2-(4-chlor o-phenyl)-2-prop-2-ynyloxyacetamide (SYN539678),

• 2-allyloxy-N-[2-(4-allyloxy-3-hydroxy-phenyl )-ethyl]-2-(4-chlor o-phenyl)-acetamide (SYN539679) and

• N-[2-(4-allyloxy-3-methoxy-phenyl)-ethyl] -2-(4-chloro-phen yl)-2-prop-2-ynyloxyacetamide (SYN536638).

SYN521195 and SYN539678 were major transforma tion products in the lake water-silt loam systems, but minor products in the lake water-loamy sand systems. SYN539679 and SYN536638 were minor products in both systems. Dissi pation of mandipropamid and formation of products in the total system occurred at a faster rate in the silt loam systems as compared to the loamy sand systems. The faster dissipation rate in the silt loam systems may have been due to greater microbial activity, with microbial biomass (as μ C/g soil) ca . 5- to 10-fold higher in the silt loam systems as compared to the loamy sand systems. 14 CO 2 was a major volatile product with maximum totals of 40.3% and 36.0% of the applied at study termination for the lake water-silt loam and lake water-loamy sand systems, respectively,72 while no [ 14 C]residues were extracted from the 7- to 3-day organic vola tiles carbon traps. Mandipropamid in the total system decreased from 96.3% of the applied at day 0 to 58.2% at 21days, 41.3% at 30 days, 9.5% at 62 days, 2.3-2.4% at 83-100 days and was 0.1% at study termination; 120-day sediment extracts we re not analyzed. In the water layer, mandipropamid decreased from 93.6% at day 0 to 51.8% at 21 days, 38.7% at 30 days, 9.5% at 62 days, 1.4% at 100 days and was 0.1% at 120 days. In the sediment, [ 14 C]mandipropamid increased from 2.7% at day 0 to 7.3% at 14 days, then decreased to 2.6% at 30 days and was ≤ 1.1% at 42-100 days. Observed DT50 values were 21-30 days in the water layer, sediment and total system. Calculated linear half-lives (r 2 = 0.4053-0.9473) were 14 days in the water layer and total system and 13 days in the sediment, while nonlinear half-lives (r 2 = 0.9406-0.9861) were 22 days in the water and total system and 12 days in the sediment. Maximum levels of the transformati on products in the water, sediment and total system were as follows: 2.8%, 5.6% a nd 8.5%, respectively, for SYN521195, 2.1%, 6.4% and 6.4%, respectively, for SYN539678, and 3.3%, 2.3% and 4.0%, respectively, for SYN539679/SYN536638. Unretained [ 14 C]residues were detected at maximums of 10.4%, 5.5% and 15.5% in the water, sediment and to tal system, respectively. In a supplementary experiment, volatilized 14 CO 2 (2M KOH) and volatile [ 14 C]organic compounds (combustion furnace/2M KOH) totaled 23.29% and 8.55% of th e applied, respectively, after 40 days of anaerobic incubation of [methoxyphenyl-U- 14 C]mandipropamid treated lake water-silt loam systems. Based on these results, the study au thor proposed that the incomplete material balances in this study were due to untrapped lo w molecular weight organic volatiles, such as methane. This study is classified as unacceptable for the following reasons:

• For both systems, material balances were incomplete with up to 46.4% and 40.0% of the applied unaccounted for in the lake wa ter-silt loam and lake water-loamy sand systems, respectively.

• For both systems, all transformation products detected at ≥ 10% of the applied may not have been identified.

162-4 Aerobic Aquatic Metabolism

MRID 46800030,31 (Supplemental)

The biotransformation of [chlorophenyl-U- 14 C]-labeled 2-(4-chl oro-phenyl)-N-[2-(3- methoxy-4-prop-2-ynyloxy-phenyl)-ethyl]-2-p rop-2-ynyloxy-acetamide (mandipropamid, NOA446510; radiochemical purity ≥ 98.6%) was studied in lake water-silt loam sediment (water pH 7.63-7.84, dissolved organic carbon < 2.0 mg/L; sediment pH 7.0-7.2, organic carbon 5.8%) and lake water-sand sediment (w ater pH 6.48-6.68, dissolved organic carbon 9.3 mg/L; sediment pH 4.9-5.3, organic carbon 0.5%) systems from the United Kingdom for 100 days under aerobic condi tions in darkness at 20 ± 2 ° C. For both systems, the sediment:water ratio used was 1:4 (45 g dry wt . sediment:180 g water). Sediment and water were pre-incubated for 13-15 days, then follo wing treatment, duplicate vessels per system type were collected after 0, 1, 2, 3, 10, 30, 45, 70 and 100 days of incubation; however, only one of the two replicates per system type wa s processed and analyzed at the 2- and 3-day73 intervals. Water layers were separated fr om the sediment via aspiration and analyzed directly. Sediment samples we re extracted either once (0-d ay sediments) or twice (all remaining sediment samples) with acetonitr ile; resulting extracts were concentrated (method/conditions not reported.

The test conditions presented in the study appe ar to have been maintained throughout the incubations. In untreated lake water-silt lo am systems incubated alongside the treated systems, conditions were moderately oxidizing in the water layers and moderately reducing in the sediment with average redox potentials of + 280 ± 25 mV and + 112 ± 11 mV, respectively, and dissolved oxygen and pH levels of 3.3 ± 0.2 mg/L and 7.23 ± 0.74, respectively, in the water. In untreated la ke water-sand systems, conditions were strongly oxidizing in the water layers and moderately to strongly oxidizing in the sediment with average redox potentials of + 485 ± 30 mV and + 392 ± 22 mV, respectively, and dissolved oxygen and pH levels of 4.0 ± 0.0 mg/L and 4.92 ± 0.16, respectively, in the water.

For both systems , the following six transformati on products were detected:

• SYN500003 (chemical name not provided),

• SYN504851 (chemical name not provided),

• SYN539678 (N-[2-(4-allyloxy- 3-hydroxy-phenyl)-ethyl]-2-(4-chloro-phenyl)-2-prop2-ynyloxy-acetamide),

• SYN539679 (2-allyloxy-N-[2-(4-allyloxy-3-hydroxy-phenyl)-et hyl]-2-(4-chlorophenyl)-acetamide),

• SYN536638 (N-[2-(4-allyloxy-3-methoxy- phenyl)-ethyl]-2-(4-chloro-phenyl)-2- prop-2-ynyloxy-acetamide) and

• SYN521195 (2-(4-chloro-phenyl)-N-[2-(3-hydr oxy-4-prop-2-ynyloxy- phenyl)-ethyl]- 2-prop-2-ynyloxy-acetamide).

SYN504851 was a major transforma tion product, while SYN500003, SYN539678, SYN539679, SYN536638 and SYN521195 were minor products. Dissipation of mandipropamid and formation of products in the tota l system occurred at a faster rate in the silt loam systems as compared to the sand systems. The faster dissipation rate in the silt loam systems may have been due to greater micr obial activity, with mi crobial biomass (as μ C/g soil) 10-fold higher in the silt loam systems as compared to the sand systems. Additionally, after application of [ 14 C]mandipropamid to the water layers, [ 14 C]residues readily partitioned from the water layer to the silt loam sediment , with movement from the water layer to the sand sediment occurring at a slower rate.

MRID 46800032 (Unacceptable)

The biotransformation of [chlorophenyl-U- 14 C]- and [methoxyphenyl-U- 14 C]-labeled 2-(4- chloro-phenyl)-N-[2-(3-methoxy-4-prop-2- ynyloxy-phenyl)-ethyl] -2-prop-2-ynyloxyacetamide (mandipropamid; NOA446510; radioche mical purities 99.1%) was studied in a simulated pond water-sandy clay loam sediment (water pH 7.91, to tal organic carbon 5.674 mg/L; sediment pH 7.2-7.7, organic carbon 1.9%) system from the United Kingdom for 120 days under natural, outdoor conditio ns. Based on the water volume, [ 14 C]mandipropamid was applied at a rate of 0.06-0.07 mg a.i. /L. The sediment:water ratio used was ca . 1:3 ( ca

. 10-cm sediment layer:30-cm water layer); the water volume was ca 648 L, but sediment weight/volume was not reported.

For both systems, conditions were moderately reducing in the water la yers and reducing to strongly reducing in the sedime nts during the initial month po sttreatment, after which redox potentials were not measured. Redox potenti als in the water layers decreased from + 177.7 to

+ 199.2 mV at 3 days to

− 5.6 to 11.9 mV at 17-31 days, wh ile in the sediment were

− 160.1 to

− 324.4 mV at 3-17 days and

− 84.2 to

− 80.6 mV at 31 days.

Observed DT50 values for mandipropamid (both la bels) were 2-7 days in the water layer and total system and 7-15 days in the sediment. In the water, sediment and total system, calculated linear half-lives (r 2 = 0.6742-0.9818) were 4, 39 and 21 days, respectively, with nonlinear half-lives (r 2 = 0.7428-0.8769) of 4, 11 and 7 days, respectively. SYN504851 was a major transformation product, with SYN521195 a major product in the chlorophenyl-label treated system and neared 10% of applied in the methoxyphenyl-label treated system. SYN539678, SYN53 9679, SYN536638 and SYN500003 were minor products. In the chlorophenyl-label treated system, SYN521195 was detected at a maximum mean 10.8% of applied in the sediment and to tal system at 15 days, decreasing to 2.5% at study termination, and was only detected at one in terval in the water at 1.1%; while in the methoxyphenyl-label treated system, SYN521195 wa s detected only in the sediment at a maximum mean 8.8% (range 7.9-9.6%). SYN 504851 was detected at maximum means of 7.2% (120 days), 4.5% (71 days) and 11.1% (120 days) in the water, sediment and total system, respectively. SYN500003 was detected at maximum means of 5.4%, 1.7% and 6.4% in the water, sediment and total sy stem, respectively. SYN539678, SYN539679 and SYN536638 were detected only in the sediment (both labels) at maximum means of 5.6- 6.9%, 0.6-0.9% and 1.1-1.9%, respectively. Unidentified [ 14 C]residues (unassigned/unaccounted for organo-and aqueous-soluble residues) were detected at maximums of 7.2-7.7%, 2.0-3.3% and 8.7-9.0% of th e applied in the water, sediment and total system, respectively. Extractable [ 14 C]residues (both labels) increased from means of 5.6-7.7% of the applied at 1 hour to maxi mum means of 24.7-31.8% at 15 days, then decreased to 6.8-14.9% at 120 days. N onextractable chlorophenyl-label [ 14 C]residues increased from a mean 0.6% at day 0 (1 and 6 hours) to 27.1% at 120 days, while methoxyphenyl-label residues increased from 0.3 -0.7% at day 0 to 29.2% at 71 days and were 20.2% at study termination. [ 14 C]Residues (both labels) in th e plant material comprised only 1.3-5.0% of the applied. In a supplemental experiment investigating the distribution depth of residues in the sediment, [ 14 C]residues were found primarily in the upper 0- to 5-cm sediment layer; quantitative resu lts were not reported. This study is classified as unacceptable for the following reasons:75 • Material balances were incomplete with up to 58.6% and 71.8% of the applied unaccounted for in the chlo rophenyl- and methoxyphenyl-l abel treated systems, respectively.

• The systems were not maintained at a constant temperature between 18 and 30 ° C.

• The systems were not maintained in continuous darkness.

163-1 Adsorption/Desorption

MRID 46800035 (Supplemental)

The adsorption/desorption charac teristics of [chlorophenyl-U- 14 C]-labeled 2-(4-chlorophenyl)-N

- [2-(3-hydroxy-4-prop-2-ynyloxy-phenyl )-ethyl]-2-prop-2-ynyloxy-acetamide (SYN521195) were studied in a silt loam soil [pH 7.6, organic carbon 2.0%] from Switzerland, a silt loam soil [pH 7.9, organi c carbon 0.8%] from France, and a sandy loam soil [pH 6.0, organic carbon 0.5%] from the United St ates, in a batch equilibrium experiment. The experimental temperature employed during the study was reported to be maintained at 19.3 ± 0.04 ° C. The pH of the test solutions after adsorption ranged from 6.89-7.33 After 48 hours of equilibration, 23.1-61.1% , 27.9-46.6%, and 17.7-36.4% of the applied [ 14 C]SYN521195 was adsorbed to the Gartenacke r silt loam, Marsillargues silt loam, and Visalia sandy loam soils, respectively (review er-calculated). The Freundlich adsorption K values were 31.0, 9.2, and 2.83 for the Gartenacke r silt loam, Marsillargues silt loam, and Visalia sandy loam soils, respec tively; corresponding Freundlich K oc values were 1537, 1145, and 567. The Freundlich desorption K values were 161.2, 49.95, and 3.34 for the Gartenacker silt loam, Marsilla rgues silt loam, and Visalia sa ndy loam soils, respectively; corresponding Freundlich desorption K oc values were 7979, 6244, and 668. This study is classified as supplemental and upgradeable upon the submission of additional information related to classification of so ils used in this study, in accordance to FAO Soil Classification (i.e. Soil Units) or equivalent U.S. So il Taxonomy. The study was conducted using three soils, and only two soil types were represented. Additional study with a fourth soil is needed fourth soil as required by the Subdivision N, Chemistry: Environmental Fate, Section 163-1

MRID 46800036 (Supplemental)

The adsorption/desorption charac teristics of [chlorophenyl-U- 14 C]-labeled SYN539678 were studied in a loam soil [pH 7.1, organic car bon 2.0%] from Switzerland, a loam soil [pH 7.8, organic carbon 0.58%] from France, and a sa ndy loam soil [pH 6.0, organic carbon 0.47%] from California, in a batch equilibrium expe riment. The equilibrating solution used was 0.01M CaCl 2 solution with a soil solution ratio of 1: 39 (w:v) for all soils. All samples were prepared in duplicate. A de sorption phase was not conducted.76 After 3 or 24 hours of equilibration, 7.6-8.9%, 15.0-23.2%, and 2.6-15.3% of the applied [ 14 C]SYN539678 was adsorbed to the Gartenacke r loam, Marsillargues loam, and Visalia sandy loam soils, respectively. The adsorp tion K values were 10.57, 12.68, and 6.17 for the Gartenacker loam, Marsillar gues loam, and Visalia sandy loam soils, respectively; corresponding K oc values were 520, 2200, and 1300. The Freundlich adsorption K values were 8.77, 11.96, and 9.19 for the Gartenacker lo am, Marsillargues loam, and Visalia sandy loam soils, respectively; corresponding Freundlich K oc values were 430, 2100, and 2000. This study is classified as unacceptable because a desorption phase was not conducted for the degradates.

MRID 46800037 (Supplemental )

The adsorption/desorption char acteristics of [phenyl-U- 14 C]-labeled (4-chloro-phenyl)-prop2-ynyloxy-acetic acid (SYN500003) were studied in a silt loam soil [Gartenacker, pH 7.6, organic carbon 2.0%] from Swit zerland, a silt loam soil [Marsillargues, pH 7.9, organic carbon 0.8%] from France, and a sandy loam soil [Visalia, pH 6.0, organic carbon 0.5%] from the United States, in a batch equilibrium experiment. The adsorption phase of the study was carried out by equilibrat ing air-dried soil with [ 14 C]SYN500003 at nominal test concentrations of 0.01, 0.05, 0.10, 0.50, and 1.00 mg a.i./kg soil, in the dark at 19.4 ± 0.1 ° C for 48 hours. The equilibrating solution used was 0.01M CaCl 2 solution with a soil solution ratio of 1:1 (w:v) for all soils. The desorption phase of the study was carried out by replacing the adsorption solution with an equivalent volume of 0.01M CaCl 2 solution and equilibrating in the dark at 19.4 ± 0.1 ° C for 24 hours. A single desorption st ep was conducted for all soils. The experimental temperature employed during the study was reported to be maintained at 19.4 ± 0.1 ° C. The pH of the test solutions af ter adsorption ranged from 7.10-7.75. After desorption, the pH ranged from 6.74-6.85.

After 48 hours of equilibration, 0.0-6.1%, 18.2-27.0%, and 1.4-30.0% of the applied [ 14 C]SYN500003 was adsorbed to the Gartenacke r silt loam, Marsillargues silt loam, and Visalia sandy loam soils, respectively. Th e Freundlich adsorption K values were 0.06, 0.23, and 0.01 for the Gartenacker silt loam, Marsillarg ues silt loam, and Visalia sandy loam soils, respectively; corresponding Freundlich K oc values were 2.92, 19.79, and 2.89. The adsorption K and K oc values were not reported. The Fr eundlich desorption K values were 0.08, 0.38, and 0.04 for the Gartenacker silt loam, Ma rsillargues silt loam, and Visalia sandy loam soils, respectively; corres ponding Freundlich desorption K oc values were 3.88, 32.52, and 8.66. The desorption K and K oc values were not reported. Th is study is classified as supplemental and upgradeable upon the submissi on of additional information related to classification of soils used in this study, in accordance to FAO Soil Classification (i.e. Soil Units) or equivalent U.S. Soil Taxonomy. Additi onal study with a fourth soil is needed as required by Subdivision N, Chemistry: Environmental Fate, Section 163-1.77 MRID 46800038, 39 (Supplemental)

The adsorption/desorption charac teristics of [methoxyphenyl-U- 14 C]-labeled 2-(4- chlorophenyl)-N-[2-(3-m ethoxy-4-prop-2-ynyloxy-phenyl )-ethyl]-2-prop-2-ynyloxyacetamide (mandipropamid; NOA446510) were st udied in a loam/silt loam soil [pH 7.1, organic carbon 2.6%] and a silt loam so il [pH 7.2, organic carbon 5.0%], each from Switzerland, a loamy sand soil [pH 5.1, organic carbon 1.0%] from Germany, and a silty clay loam soil [pH 7.3, organic carbon 1.2%] from Fr ance, in a batch equilibrium experiment. The adsorption phase of the study was carried out by equilibrating air-dried soil with [ 14 C]mandipropamid at nominal test concentrations of 0.16, 0.81, 1.61, 3.23, and 8.06 mg a.i./kg soil (loam/silt loam); 0.06, 0.30, 0.60, 1.20, and 3.0 mg a.i./kg soil (loamy sand); 0.08, 0.40, 0.79, 1.59, and 3.97 mg a.i./kg soil (silty clay loam); and 0.25, 1.25, 2.5, 5.0, and 12.5 mg a.i./kg soil (silt loam ), in the dark at 20.3 ± 0.3 ° C for 24 hours. The equilibrating solution used was 0.01M CaCl 2 solution with a soil solution ratio of 3.1:50 (w:v; loam/silt loam); 8.3:50 (w:v; loamy sand); 6.3:50 (w:v; silty clay loam); and 2.0:50 (w:v; silt loam). The desorption phase of the study was carried out by replacing the adsorption solution with an equivalent volume of 0.01M CaCl 2 solution and equilibrating in the dark at 20.3 ± 0.3 ° C for 24 hours. Two desorption steps were performed for each test soil. The experimental temperature employed during the study wa s reported to be maintained at 20.3 ± 0.3 ° C. The pH of the test solutions during the study wa s not reported. After 24 hours of equilibration, 65.0-93.8%, 77.1-100.8%, 60.8-81.9%, and 69. 5-80.6% of the applied [ 14 C]mandipropamid was adsorbed to the Gartenacker loam/silt loam , Borstel loamy sand, Marsillargues silty clay loam, and Vetroz silt loam soils. The Fr eundlich adsorption K values were 20.3, 12.9, 12.6, and 53.2 for the Gartenacker loam/silt loam, Borstel loamy sand, Marsillargues silty clay loam, and Vetroz silt loam soils, respectively; corresponding Freundlich K oc values were 782, 1294, 1067, and 1064. The adsorption K and K oc values were not reported. Following the second desorption step, the percent of [ 14 C]mandipropamid desorbed fr om the test soils, as percent of the radioactivity adsorbed, was 30.8-46.9% for the Gartenacker loam/silt loam, 25.4-36.0% for the Borstel loamy sand, 19.5-36.3% for the Marsillargues silty clay loam, and 30.9-38.9% for the Vetroz silt loam soil. Th e Freundlich desorption K values were 32.9, 20.8, 21.7, and 86.8 for the Gartenacker loam/silt loam, Borstel loamy sand, Marsillargues silty clay loam, and Vetroz silt loam soils , respectively; corresponding Freundlich desorption K oc values were 1271, 2076, 1836, and 1736. The desorption K and K oc values were not reported. This study is classi fied as supplemental and upgr adeable upon the submission of additional information related to classification of soils used in this study, in accordance to FAO Soil Classification (i.e. Soil Units) or equivalent U.S. Soil Taxonomy. Additional study with a fourth soil is needed as required by Subdivision N, Chemistry: Environmental Fate, Section 163-1.78 MRID 46800040, 41 (Supplemental) The adsorption/desorption characteristics of [methoxyphenyl-U- 14 C]-labeled 2-(4-chlorophen yl)-N-[3-methoxy-4-(prop-2- ynyloxy)phenylethyl]-2-(prop-2- ynyloxy)acetamide (mandipropamid; NOA446510) were studied in a sandy loam soil [pH 6.6, organi c carbon 0.52%] from California, a loamy sand soil [pH 4.9, organic carbon 0.70%] from Georgia, and a loamy sand soil [pH 6.7, organic carbon 1.16%] from New York, in a batch equili brium experiment. The adsorption phase of the study was carried out by equili brating air-dried soil with [ 14 C]mandipropamid at nominal test concentrations of 0.05, 0.25, 0.50, 1.00, and 3.00 mg a.i./kg soil (Sanger sandy loam); 0.05, 0.23, 0.45, 0.90, and 2.70 mg a.i./kg soil (Chula loamy sand); and 0.07, 0.37, 0.74, 1.47, and 4.41 mg a.i./kg soil (North Rose loamy sand) , in the dark at 19.4 ± 0.2 ° C for 24 hours. The equilibrating solution used was 0.01M CaCl 2 solution with a soil solution ratio of 10.0:50 (w:v; Sanger sandy loam); 11.1:50 (w:v; Chula loamy sand); and 6.8:50 (w:v; North Rose loamy sand). The experimental temperat ure employed during the study was reported to be maintained at 19.4 ± 0.2 ° C; supporting data were not provided. The pH of the test solutions after adsorption ranged from 5.01 to 7.08. The pH of the test so lutions ranged from 6.16 to 7.03 at the first desorption step (one desorption step for all test concentrations except high-dose), 6.14 to 7.03 during the second desorpti on step (high dose only), and from 6.01 to 7.08 during the third desorption step (high dose only). After 24 hours of equilibration, 47.2- 71.0%, 46.3-72.0%, and 55.7-91.4% of the applied [ 14 C]mandipropamid was adsorbed to the Sanger sandy loam, Chula loamy sand, and North Rose loamy sand soils, respectively. The Freundlich adsorption K values were 3.68, 2.88, and 7.37 for the Sanger sandy loam, Chula loamy sand, and North Rose loamy sand soils , respectively; corresponding Freundlich K oc values were 693.9, 405.1, and 624.3. The adsorption K and K oc values were not reported. Following the first desorption step, the percent of [ 14 C]mandipropamid desorbed from the test soils, as percen t of the radioactivity adsorbed, was 21.4-40.1% for the Sanger sandy loam, 19.2-40.9% for the Chula loamy sand, and 21.9-34.9% for the North Rose loamy sand. Following the third desorption step, the percent of [ 14 C]mandipropamid desorbed from the high-dose soils was 69.3%, 68.0%, and 63.2% fo r the Sanger sandy loam, Chula loamy sand, and the North Rose loamy sand soils, respec tively (reviewer-calcula ted). The Freundlich desorption K values were 4.98, 4.33, and 11.86 for the Sanger sandy loam, Chula loamy sand, and North Rose loamy sand soils, respectively; corre sponding Freundlich desorption K oc values were 939.6, 609.9, and 1004.8. For th e high-dose soils following the third desorption step, Freundlich desorption K values were 2.39, 1.63, and 4.13 for the Sanger sandy loam, Chula loamy sand, and North Rose loamy sand soils, respectively; corresponding Freundlich desorption K oc values were 423, 229, and 229. The desorption K and K oc values were not reported for any of the te st soils. This study is classified as supplemental and upgradeable upon the submissi on of additional information related to classification of soils used in this study, in accordance to FAO Soil Classification (i.e. Soil Units) or equivalent U.S. Soil Taxonomy. Th e study was conducted using three soils, and only two soil types were repr esented. Additional study with a fourth soil is needed as required by the Subdivision N, Chemistry: Environmental Fate, Section 163-179 MRID 46800042, 43 (Supplemental)

The adsorption/desorption charac teristics of [methoxyphenyl-U- 14 C]-labeled 2-(4-chlorophenyl)-2-hydroxy-N

- [2-(3-methoxy-4-prop-2-ynyloxy-phenyl)-ethyl]acetamide (CGA380778) were studied in a sandy clay loam soil [pH 5.6, organic carbon 3.25%] from the United Kingdom, a loam soil [pH 7.2, orga nic carbon 2.06%] from Switzerland, and a sandy loam soil [pH 6.3, organic carbon 0.46%] from the United States, in a batch equilibrium experiment. The adsorption phase of the study was carried out by equilibrating air-dried soil with [ 14 C]-CGA380778 at actual concen trations of 0.23, 0.61, 1.18, 6.19, and 11.85 mg a.i./kg soil (18 Acres sandy clay loam and Gartenacker loam); and 0.11, 0.31, 0.59, 3.09, and 5.93 mg a.i./kg soil (Visalia sandy loam), in the dark at 25 ± 0.1 ° C for 48 hours. The equilibrating solution used was 0.01M CaCl 2 solution with a soil solution ratio of 1.0:12.5 (w:v; 18 Acres sandy clay loam and Ga rtenacker loam); and 1.0:6.25 (w:v; Visalia sandy loam). The desorption phase of the st udy was carried out by re placing the adsorption solution with an equivalent volume of 0.01M CaCl 2 solution and equilibrating in the dark at 25 ± 0.1 ° C for 48 hours. A single desorption st ep was conducted for all soils. The experimental temperature employed during the study was reported to be maintained at 25 ± 0.1 ° C. The pH of the test solutions during th e study ranged from 6.2-6.5. After 48 hours of equilibration, 58.0-68.3%, 46.3-59.5%, and 21.0-39.0% of the applied [ 14 C]CGA380778 was adsorbed to the 18 Acres sandy clay loam, Ga rtenacker loam, and Visalia sandy loam soils, respectively. The Freundlich adsorption K values were 15.7, 10.3, and 1.7 for the 18 Acres sandy clay loam, Gartenacker loam, and Visalia sandy loam soils, respectively; corresponding Freundlich K oc values were 482, 501, and 361. The adsorption K and K oc values were not determined. At the end of the desorption phase, the percent of [ 14 C]CGA380778 desorbed from the test soils, as percent of the radioactivity adsorbed, was 93.0-174.2% for the 18 Acres sandy clay loam , 49.3-100.8% for the Gartenacker loam, and 10.2-40.9% for the Visalia loam soils. The Freundlich desorption K values were 20.0, 13.5, and 3.8 for the 18 Acres sandy clay loam, Gart enacker loam, and Visalia sandy loam soils, respectively; corresponding Freundlich desorption K oc values were 615, 654, and 818. This study is classified as supplemental a nd upgradeable upon the submission of additional information related to classifi cation of soils used in this study, in accordance to FAO Soil Classification (i.e. Soil Units ) or equivalent U.S. Soil Taxonomy. The study was conducted using three soils. Additional study with a fourth soil is needed as required by the Subdivision N, Chemistry: Environmental Fate, Section 163-1

164-1 Terrestrial Field Dissipation

MRID 46800045 (Acceptable)

Soil dissipation/accumulation of mandipropamid (4-chloro- N -[2-[3-methoxy-4-(2- propynyloxy)phenyl]ethyl]- α -(2-propynyloxy)benzeneacetamide) under U.S. field conditions was conducted in bare plots of sandy loam soil at one site in California. Mandipropamid was broadcast four times (7-day inte rvals) at a target rate of 0.16 5 kg a.i./ha (0.147 lb a.i./A) to a80 21 x 43 m test plot divided into three replicate areas. The tota l target rate applied was 660 g a.i./ha or 110% of the proposed maximum annua l rate for leafy vegetables. The application was made to approximate the timing of typical fu ngicide applications in the fall for control of foliar oomycete pathogens on leafy vegetables in the San Joaquin Valley of California. Total water input during the study peri od was 70.32 inches or over 300% of the 30-year historical average precipitation. A control plot was located approximately 59 m from the treated plot.

Soil samples were collected at 0, 1, and 6 days fo llowing the first three applications and at 0, 1, 3, 7, 14, 21, 30, 58, 90, 125, 182, 272, 359, 454, and 540 days following the fourth application to a depth of 0-120 cm (except app lication 1, day-0 samples which were collected to a depth of 15 cm).

The measured zero-time recovery of mandipropamid in the 0-15 cm soil layer was 56 ppb or 70% of the theoretical. Mandipropamid was de tected in the 0-15 cm soil layer at 97 ppb following the second application, 146 ppb following the third application, and at a maximum of 165 ppb following the fourth applica tion. Following the f ourth application, mandipropamid decreased to 83 ppb by 58 days, 31 ppb by 182 days, 4.1 ppb by 272 days, and ranged from 2.1-2.6 ppb from 359 to 540 da ys posttreatment. Mandipropamid was not detected below the 0-15 cm soil depth. No tran sformation products were detected in the soil at greater than 10% of the applied mandipropa mid. Under field conditions at the test site, mandipropamid had a half-life va lue of 75.3 days in soil (r 2 = 0.9158), calculated using linear regression and the equation t 1⁄2 = ln 2 / k, where k is the rate constant, and based on all available data following the fourth applic ation. The major rout e of dissipation of mandipropamid under terrestrial field conditi ons could not be determined because transformation products were detected at <2 % of the applied mandipropamid, leaching and carryover of residues were not observed, and volatilization and runoff were not studied. However, the study author stated that no ma jor degradation product was identified in the laboratory environmental fate studies.

MRID 46800046 (Acceptable)

Soil dissipation/accumulation of mandip ropamid (4-chloro-N-[2-[3-methoxy-4-(2- propynyloxy)phenyl]ethyl]- α -(2-propynyloxy)benzeneacetamide) under U.S. field conditions was conducted in a bare plot a nd a cropped plot (potatoes) of loamy sand soil at one site in New York. Mandipropamid was broadcas t four times (6- to 7-day inte rvals) at a target rate of 0.165 kg a.i./ha (0.147 lb a.i. /A) to two 29 x 35 m test plots ea ch divided into three replicate areas. The total target rate applied was 660 g a.i./ha or 110% of the proposed maximum annual rate for potatoes. The potato crop was at the late bloom stage (20-inch height) at the first application and at the pos t bloom stage (24-inch height) at subsequent applications; coverage was 70% at the first application a nd 85-90% by the fourth application. The crop was harvested 57 days after the fourth applica tion. The application was made to approximate the timing of typical fungicide applications fo r control of oomycete pathogens (late blight) on potatoes in the Northeastern region of the U. S. Total water input during the study period was81 80.60 inches or 142% of the 30-year historical average precipitation. A control plot was located approximately 70 m from the nearest trea ted plot. Soil samples were collected at 0, 1, and 5 days following the first application, at 0, 1, and 6 days following the second and third applications, and at 0, 1, 3, 7, 14, 21, 30, 65, 91, 124, 194, 275, 356, 448, and 505 days following the fourth application to a depth of 0-120 cm (excep t application 1, day-0 samples which were collected to a depth of 15 cm).

In the bare plot , the measured zero-time recovery of mandipropamid in the 0-15 cm soil layer was 68 ppb or 79% of the theoretical. Mandipropam id was detected in the 0-15 cm soil layer at 100 ppb following the second application, 136 ppb following the third application, and 120 ppb following the fourth application. Followi ng the fourth app lication, mandipropamid decreased to 63-65 ppb by 7-21 days, 43-54 ppb by 30-194 days, 12 ppb by 275 days, and ranged from 2.7-4.4 ppb from 356 to 505 days posttreatment. Mandipropamid was not detected below the 0-15 cm soil depth. No tran sformation products were detected in the soil at greater than 10% of the appl ied mandipropamid. In the cropped plot , the measured zerotime recovery of mandipropamid in the 0- 15 cm soil layer was 52 ppb or 60% of the theoretical. Mandipropamid was detected in the 0-15 cm soil layer at 53 ppb following the second application, 90 ppb following the third application, and 101 ppb following the fourth application. Following the four th application, mandipropamid increased to a maximum of 167 ppb by 65 days, coinciding with the sampling in terval following the ha rvest of the potato crop at 57 days posttreatment, when residues bou nd to the potato leaves were incorporated into the soil. Following 65 days, mandipropamid decreased to 68 ppb by 194 days, 20-21 ppb by 356-448 days, and was 16 ppb at 505 days posttreatment. Mandipropamid was not detected below the 0-15 cm soil depth. No tran sformation products were detected in the soil at greater than 10% of the applied mandipropa mid. Under field conditions in the bare plot

, mandipropamid had a half-life value of 100.5 days in soil (r 2 = 0.8628), calculated using linear regression a nd the equation t 1⁄2 = ln 2 / k, where k is the rate constant, and based on all available data following the fourth application. However, dissipation was bi-phasic, with a more rapid decline phase during the first month of the study; th e half-life based on 0-30 day data was 27.8 days (r 2 = 0.5521).

Under field conditions in the cropped plot , mandipropamid had a half-life value of 126 days in soil (r 2 = 0.9384), calculated using linear regression and the equation t 1⁄2 = ln 2 / k, where k is the rate constant, and based on all availa ble data following the maximum detection of mandipropamid at 65 days following the fourth application. The major route of dissipation of mandipropamid under terrestrial field conditi ons could not be determined because transformation products were detected at <2 % of the applied mandipropamid, leaching and carryover of residues were not observed (carr yover was <5%), and vol atilization and runoff were not studied. However, the study author stated that there was no major degradation product identified in the laborator y environmental fate studies.

MRID 46800047 (Acceptable)

Soil dissipation/accumulation of mandipropamid (4-chloro- N -[2-[3-methoxy-4-(2- propynyloxy)phenyl]ethyl]- α -(2-propynyloxy)benzeneacetamide) under US field conditions82 was conducted in bare plots of loamy sand soil at one site in Georgia. Mandipropamid was broadcast four times (7-day inte rvals) at a target rate of 0.16 5 kg a.i./ha (0.147 lb a.i./A) to a 35 x 35 m test plot divided into three replicate areas. The tota l target rate applied was 660 g a.i./ha or 110% of the proposed maximum annua l rate for squash. The applications were made to approximate the timing of typical fungici de applications in the spring for control of oomycete pathogens on squash in the Southeastern region of the U.S. Total water input during the study period was 138.54 inches or 189 % of the 30-year historical average precipitation. A control plot was located a pproximately 46 m from the treated plot. Soil samples were collected at 0, 1, and 6 days follo wing the first three app lications and at 0, 1, 3, 7, 14, 21, 30, 62, 93, 120, 183, 268, 364, 457, and 540 days following the fourth application to a depth of 0-120 cm (except application 1, da y-0 samples which were collected to a depth of 15 cm). The measured zero-time recovery of mandipropamid in the 0-15 cm soil layer was 58 ppb or 76% of the theoretical. Mandipropamid wa s detected in the 0-15 cm soil layer at 86 ppb following the second application, a maximu m of 136 ppb following the third application, and 124 ppb following the fourth application. Following the f ourth application, mandipropamid decreased to 60 ppb by 21 days, 19 ppb by 62 days, 4.0-5.9 ppb by 268-364 days, and was 0.74 ppb at 540 days posttreatment . Mandipropamid was only detected in the 15-30 cm soil depth once, at 0.53 ppb at 14 days posttreatment, and was not detected below that depth. No transformation products were det ected in the soil at gr eater than 10% of the applied mandipropamid. Under field conditions at the test site, mandipropamid had a half-life value of 81.5 days in soil (r 2 = 0.8934), calculated using linear regression and the equation t 1⁄2

= ln 2 / k, where k is the rate constant, and base d on all available data following the fourth application. However, dissipation was bi-phasic, with a more rapid decline phase during the first two months of the study; the half- life based on 0-62 day data was 24.5 days (r 2 = 0.9090). The major route of dissi pation of mandipropamid under te rrestrial field conditions could not be determined because transforma tion products were detected at <2% of the applied mandipropamid, leaching and carryover of residues were not observed, and volatilization and runoff were not studied. However, the study aut hor stated that there was no major degradation product identified in th e laboratory environmental fate studies.

The important metabolites formed by the degr adation of mandipropa mid are provided in Table A-7 and the chemical structures of these metabolites are illustrated in Table A-8

.83 Table A-7. Maximum Amounts of Mandipropam id Metabolites in Degradation Studies Characterized by Study Type Study Type Metabolite (% Maximum) MRID 161-1 Hydrolysis No degradation products observed 46800007,8 161-2 Aqueous photolysis Polar compounds totaled average of 36.7%.

Unidentified polar compounds totaled a maximum of 25.0%.

Unidentified minor residues maximum of ≤ 6.2% of the applied

minor nonpolar transformation products, none averaging > 5% of the applied 46800009

46800010

46800011,12

46800013,14

161-3 Soil photolysis CO 2 (6.3%) CGA380775 (4.1%) SYN505503 (3.0%) CGA380778 (2.5%) NOA495119 (0.2%) NOA458422 (0.7%) SYN521195 (not quantified)

CO 2 (17.1%) CGA380778 (3.9%)

CO 2 (`14.98%) CGA380778 (3.80%) 46800015

46800016,17

46800018,19

162-1 Aerobic soil metabolism CO 2 (maximum 56.3% CGA380778 (4.25%) CGA380775 (0.51%) SYN500003 (0.27%) NOA458422 (0.18%)

CGA380778 (2.9%)

CO 2 (maximum 51.0%)

CO 2 (21.8%) CGA380778 (1.4%) SYN536638 (2.4%) NOA458422 (below limit of detection

CGA380778 (3.2%)

CO 2 (12.3%) CGA380778 (4.8%) 46800020,21

46800022

46800023

46800024,25

46800027

4680002884 Table A-7. Maximum Amounts of Mandipropam id Metabolites in Degradation Studies Characterized by Study Type Study Type Metabolite (% Maximum) MRID 162-2 Anaerobic soil metabolism CO 2 was the only significant degradation product. CGA380778(4.6%) 46800022

162-3 Anaerobic aquatic metabolism SYN500003 (25.9%) YN504851 (73.5%) YN521195 (10.3%) O 2 (15.8%) YN539678 (4.6%) YN539679 (6.1%)

SYN536638 (0.9%) 46800030,31

162-4 Aerobic aquatic metabolism SYN521195 (10.8%) SYN504851 (11.1%) SYN500003 (6.4%) SYN539678 (6.9%) SYN539679 (0.9%) SYN536638 (1.9) 4680003285 Table A-8. The Chemical Structure of NOA446510 (Mandipropamid) and its Metabolites CH
C
CH

2 O
C H 2

Cl N O CH 3

O C H 2

C H 2 O
C CH NOA446510

Cl O N O

C H 2 C H 2

OH OH CH 2 C CH

SYN505503

Cl OH

O N C H 2 C H 2

O O CH 3

C H 2 C CH

CGA380778

Cl O N OH

C H 2 C H 2

OH O CH 3

CGA38077586 Table A-8. The Chemical Structure of NOA446510 (Mandipropamid) and its Metabolites

Cl O

O N CH

2 C CH

C H 2 C H 2

O O

C H 2 C CH 3

SYN536638

Cl O

O N CH

2 C CH

C H 2 C H 2

O OH

C H 2 C CH SYN521195

Cl O

O N CH

2 C CH

C H 2 C H 2

O OH

C H 2 C

SYN53967887 Table A-8. The Chemical Structure of NOA446510 (Mandipropamid) and its Metabolites

Cl O

O OH CH

2 C

SYN504851

Cl O

O N CH

2 C

C H 2 C H 2

O OH

C H 2 C

SYN53967988 

# Appendix B. GENEEC Aquatic Exposure Model

The GENEEC ( GEN eric E stimated E nvironmental C oncentration) model, the tier one computer program, uses the soil/water partiti on coefficient and degradation kinetic data to estimate runoff from a ten hectare field into a one hectare by two meter deep "standard" pond. This first tier is designed as a coarse screen and estimates conservative pesticide concentrations in surface water from a few basi c chemical parameters and pesticide label use and application information. Tier 1 is used to screen chemicals to determine which ones potentially pose sufficient risk to warrant higher level modeling. Chemicals failing to pass this program, move on to the tier two modeling. As a matter of policy, OPP does not take significant adverse regulatory action based upon the results of tier 1 screening models.

GENEEC is a program to calculate acute as well as longer-term estimated environmental concentration (EEC) values. It considers reduction in dissolved pesticid e concentration due to adsorption of pesticide to soil or sediment, in corporation, degradation in soil before washoff to a water body, direct deposition of spray dr ift into the water body, a nd degradation of the pesticide within the water body (( http://www.epa.gov/oppefed1/models/water /geneec2_users_manual.htm#introduction )). 

# GENEEC Output

**RUN No. 1 FOR Total Residue ON all * INPUT VALUES ***

**-------------------------------------------------------------------- RATE (#/AC) No.APPS & SOIL SOLUBIL APPL TYPE NO-SPRAY INCORP**  **ONE(MULT) INTERVAL Koc (PPM ) (%DRIFT) ZONE(FT) (IN)**

**-------------------------------------------------------------------- .130( .477) 4 7 2.9** ***** AERL_B( 13.0) .0 .0**

**FIELD AND STANDARD POND HALFLIFE VALUES (DAYS)**

**-------------------------------------------------------------------- METABOLIC DAYS UNTIL HYDROLYSIS PHOTOLYSIS METABOLIC COMBINED**  **(FIELD) RAIN/RUNOFF (POND) (POND-EFF) (POND) (POND)**

**-------------------------------------------------------------------- 72.04 2 N/A 1.10- 136.40 102.00 58.36** 

**GENERIC EECs (IN MICROGRAMS/LITER (PPB)) Version 2.0 Aug 1, 2001**

**-------------------------------------------------------------------- PEAK MAX 4 DAY MAX 21 DAY MAX 60 DAY MAX 90 DAY** 
**GEEC AVG GEEC AVG GEEC AVG GEEC AVG GEEC**

**-------------------------------------------------------------------- 20.88 20.67 19.42 16.92 15.29** 89 

# APPENDIX C. Explanation of T-REX Model

1. Introduction

This spreadsheet based model calculates the decay of a chemical applied to foliar surfaces for single or multiple applications. It uses the same principle as the batch code models FATE and TERREEC for calculating terrestrial estimates exposure (TEEC) concentrations on plant surfaces following application. A first-order decay assumption is used to determine the concentration at each day after initial applicat ion based on the concentration resulting from the initial and additional applications. The decay is calculated by from the first-order rate equation:

C T = C i e -kT

or in log form:

ln (C T /C i ) = kT

where:

C T = concentration at time T = day zero.

C i = concentration, in parts per million (ppm ) present initially (on day zero) on the surfaces. C i is calculated based on Kenaga and Fletcher by multiplying the C i based on the Kenaga nomogram (Hoerger and Kenaga [1972] as modified by Fletcher [1994]). For maximum concentr ation the application rate, in pounds active ingredient per acre, is multipli ed by 240 for short grass, 110 for tall grass, and 135 for broad leafed plants/small insects and 15 for fruits/pods/large insects. Additional a pplications are converted from pounds active ingredient per acre to ppm on the plant surface and the additional mass added to the mass of the chemical still present on the surfaces on the day of application.

k = If the foliar dissipation data submitte d to EFED are found scientifically valid and statistically robust for a specific pesticide, th e 90% upper-confidence limit of the mean half-lives sh ould be used. When scientif ically valid, statistically robust data are not available TETT recomme nds the use of a default half-life value of 35 days. The use of the 35 day half-life is based on the highest reported value (36.9 days) reported by Willis and McDowell (1987).

T = time, in days, since the start of the simulation. The initial application is on day 0. The simulation is designed to run for 365 days.90 The program calculates concentration on each type of surface on a daily interval for one year. The maximum concentrations during the year are calculated for both maximum and mean residues. The inputs required are:

Application rate: The maximum label appli cation rate (in pounds a.i./acre) Half-life: The degradation half-life for the dominate process (in days) Frequency of application: The interval between repeated applications, from the label (in days) Maximum number of application per year: From the label

The calculated concentrations are used to cal culate Avian and Mammalian RQ values. The maximum calculated concentration is divided by user input values for acute and chronic endpoints to give RQs for each type of plant surface.

2. Avian Species

For calculating dose-based RQs in birds, the ma ximum and mean Kenaga residue values are adjusted for avian class and food consumption based on the following scaling factor (USEPA 1993):

FI (g/d) = 0.648 (g bw)^0.651

For the three avian weight classes considered (20, 100, and 1000 g), this re sults in percent of body weight consumption of:

Weight (g) FI Wet FI % Body Weight Consumed
20 4.555599463 22.77799731 114 100 12.98897874 64.94489369 65 1000 58.15338588 290.7669294 29

A. Dose-Based Acute RQs

Dose-based acute RQs are then calculated using the formula:

RQ = adjusted EEC/LD 50 or NOAEL

where the adjusted EEC is considered to be the daily dose weighted for percent of body weight consumed of a given food source.91 B. Dietary-Based RQs

For dietary-based RQs, two values are give n for each food group. First, the consumptionweighted RQ for each weight class (20, 100, and 1000 g birds) is displayed and calculated using the equation:

RQ = EEC/((LC 50 or NOAEC)/(%bw consumed))

In the second method, no adjustment is made for consumption differences among the weight classes. This RQ is calculated:

RQ = EEC/LC 50 or NOAEC

3. Mammalian Species

A. Dose-Based RQs

For calculating dose-based RQs in mammals, th e maximum and mean Kenaga values are adjusted for mammalian class and food c onsumption (0.95, 0.66, and 0.15 body weight for herbivores and insectivores and 0.21, 0.15, and 0.03 body weight for granivores). Dose-based acute and chronic RQs are then calculated by dividing the adjusted EECs (daily dose) by the LD 50 or NOAEL.

B. Dietary-Based RQs

Dietary-based RQs are calculated using the equation:

RQ = EEC/((LC 50 or NOAEC)/(% bw consumed))

4. Graph

A graph of concentration on each plant surface vs. time is plotted and a concentration of concern line can be added at a user specified le vel. The concentration of concern (e.g., avian LC 50 , mammalian NOAEL) label should be entere d in the cell undernea th the value. The graph automatically plots a line at this concentra tion and the label is extracted from that cell. The graph is plotted for the first 100 days post-application. Graphs displaying acute and chronic LOCs for both birds and mammals are displayed in the "Graph" worksheet. These graphs may be useful as a vi sual aid to communicate risk in your assessment and can be copy/pasted into your document. To help with scaling issues on the y axis, you may want to delete one of the endpoints.

5. New Version Notes

A new look is used in this update in an effort to decrease c onfusion and increase transparency in the risk assessment process. This version of T-REX (v1.3.1) incorporates the ability to calculate EECs and RQs for maximum and mean residues. Mean residues are calculated92 exactly as the maximum residue s are, except the co rresponding Kenaga va lues are: 85 for short grass, 36 for tall grass, and 45 for br oad leafed plants/small insects and 7 for fruits/pods/large insects.93 

# Appendix D. Explanation of TerrPlant Model

Introduction

Exposure to Terrestrial Plants includ ing Wetlands (December 26, 2005; version 1.2.1)

The change to this model version is the remova l of the 60% efficiency factor for aerial applications.

Terrestrial plants inhabiting dry and semi-aquatic (wetland ) areas may be exposed to pesticides from runoff and/or sp ray drift. Semi-aquatic areas are low-lying wet areas that may dry up at times throughout the year.

EFED's runoff scenario is:

(1) based on a pesticide's water solubility and the amount of pesticide present on the soil surface and its top one centimeter;

(2) characterized as "sheet runoff" (one treate d acre to an adjacent acre) for dry areas;

(3) characterized as "channel runoff" (10 acr es to a distant low-lying acre) for semiaquatic or wetland areas; and

(4) based on percent runoff values of 0.01, 0.02, and 0.05 for water solubilities of <10, 10–100, and <100 ppm, respectively.

EFED's Spray Drift scenario is assumed as: (1 ) 1% for ground application; and (2) 5% for aerial, airblast, forced air, and spray chemigation applications.

The spray drift ratio used here is in agreement with the pol icy procedures at the time the worksheet was designed.

Currently, (1) this worksheet is designed to de rive the plant exposure concentrations from a single, maximum application rate only; and (2) for pesticide applications with incorporation of depth of less than 1 inch, the total loadi ng EECs derived for the incorporation method will be same as the unincorporated method.

To calculate RQ values for Non-Endangered Terrestrial Plants:

Terrestrial Plants Inhabiting Areas Adjacent to Treatment Site:

Emergence RQ = Total Loading to Ad jacent Area or EEC/Seedling Emergence EC 25 Drift RQ = Drift EEC/Vegetative Vigor EC 2594 Terrestrial Plants Inhabiti ng Semi-aquatic Areas Adjacent to Treatment Site:

Emergence RQ = Total Loading to Semi-a quatic Area or EEC/Seedling Emergence EC 25 Drift RQ = Drift EEC/Vegetative Vigor EC 25
To calculate RQ values for Endangered Terrestrial Plants:

Endangered Terrestrial Plants Inhabiting Areas Adjacent to Treatment Site:

Emergence RQ = Total Loading to Ad jacent Area or EEC/Seedling Emergence EC 05 or NOAEC Drift RQ = Drift EEC/Vegetative Vigor EC 05 or NOAEC

Endangered Terrestrial Plants Inhabiting Se mi-aquatic Areas Near Treatment Site:

Emergence RQ = Total Loading to Semi-a quatic Area or EEC/Seedling Emergence EC 05 or NOAEC Drift RQ = Drift EEC/Vegetative Vigor EC 05 or NOAEC

Background for EEC Calculation

Formulas used to calculate EEC values (November 9, 2005; version 1.2.1)

To calculate EECs for terrestrial plants inhabi ting in areas adjacent to treatment sites:

Un-incorporated Ground Application (Non-granular):

Sheet Runoff = Application Rate (lbs a.i./acre) x Runoff Value Drift = Application Rate (lbs a.i./acre) x 0.01 Total Loading = EEC = Sheet Runoff + Drift

Incorporated Ground Application with Drift (Non-granular):

Sheet Runoff = [Application Rate (lbs a.i. /acre)/Incorporation Depth (cm)] x Runoff Value Drift = Application Rate (lbs a.i./acre) x 0.01 Total Loading = EEC = Sheet Runoff + Drift

Un-incorporated Ground Application (Granular):

Sheet Runoff = EEC = Application Rate (lbs a.i./acre) x Runoff Value

Incorporated Ground Application without Drift (Granular):

Sheet Runoff = EEC = [Application Rate (lbs a.i./acre)/Incorporation Depth (cm)] x Runoff Value95 Aerial/Airblast/Spray Chemigation Applications 1 :
Sheet Runoff = Application Rate (lbs a.i./acre) x Runoff Value Drift = Application Rate (lbs a.i./acre) x 0.05 Total Loading = EEC = Sheet Runoff + Drift

Runoff Value = 0.01, 0.02, or 0.05 when the solubili ty of the chemical is <10 ppm, 10-100 ppm, or >100 ppm, respectively. Incorporation Depth: Use the minimum incorporation depth reported on the label.

Formulas used to calculate EEC values:

To calculate EECs for terrestrial plants i nhabiting semi-aquatic low-lying areas near treatment sites:

Un-incorporated Ground Application (Non-granular):

Channelized Runoff = Application Rate (lbs a.i./acre) x Runoff Value x Factor 10 Drift = Application Rate (lbs a.i./acre) x 0.01 Total Loading = EEC = Channelized Runoff + Drift

Incorporated Ground Application with Drift (Non-granular):

Channelized Runoff = [Application Rate (lbs a.i./acre)/Incorporat ion Depth (inch)] x Runoff Value x Factor 10 Drift = Application Rate (lbs a.i./acre) x 0.01 Total Loading = EEC = Channelized Runoff + Drift

Un-incorporated Ground Application (Granular):

Channelized Runoff = EEC = Application Rate (lbs a.i./acre) x R unoff Value x Factor 10

Incorporated Ground Application without Drift (Granular):

Channelized Runoff = EEC = [Application Ra te (lbs a.i./acre) /Incorporation Depth (inch)] x Runoff Value x Factor 10

Aerial/Airblast/Spray Ch emigation Applications:

Channelized Runoff = Application Rate (lbs a.i./acre) x Runoff Value x Factor 10 Drift = Application Rate (lbs a.i./acre) x 0.05 Total Loading = EEC = Channelized Runoff + Drift96 Runoff Value = 0.01, 0.02, or 0.05 when the solubili ty of the chemical is <10 ppm, 10-100 ppm, or >100 ppm, respectively. Factor 10 repr esents 10 treated acres per acre of low-lying area. Incorporation Depth: Use the minimu m incorporation depth reported on the label.97 

# Appendix E. Description of Ecological Effects Studies

a. Toxicity to Terrestrial Animals

I. Birds, Acute and Subacute

An acute oral toxicity study using the technical grade of th e active ingredient (TGAI) is required to establish the toxicity of mandipropamid to birds. The preferred test species is either mallard duck (a waterfowl) or bobwhite quail (an upland gamebird). Results of this test are tabulated below.

Avian Acute Oral Toxicity

Species % a.i. LD50 (mg/kg a.i.) Toxicity Category MRID No. Study Classification 1

Mallard Duck ( Anas platyrhychos ) 96.5 > 1000 Practically nontoxic 468001-11 Acceptable

Northern Bobwhite Quail ( Colinus virginianus ) 96.5 > 2250 Practically nontoxic 468001-10 Acceptable

The results of these studies de monstrate that mandipropamid is practically nontoxic to avian species on an acute oral basis.

Two subacute dietary studies using the TGAI are required to establish the toxicity of mandipropamid to birds. The preferred test species are mallard duck and bobwhite quail. Results of these tests are tabulated below.

Avian Subacute Dietary Toxicity

Species % a.i. 5-Day LC50 (ppm a.i.) Toxicity Category MRID No. Study Classification 1

Mallard Duck ( Anas platyrhychos ) 96.5 > 6080 Practically Nontoxic 468001-12 Acceptable

Northern Bobwhite Quail ( Colinus virginianus ) 96.5 > 6080 Practically Nontoxic 468001-13 Acceptable98 The results of the avian acute dietary studies indicate mandipropamid is practically nontoxic to avian species on a subacute dietary basis.

ii. Birds, Reproductive Toxicity

Two avian reproduction studies testing mandipropamid were submitted to the Agency. The details of these studies are illustrated in the following table. The results of these studies demonstrated no significant effects to either avian reproduction or growth.

Avian Reproductive Toxicity

Species/ Exposure Duration % a.i. Test Type Toxicity Value (ppm) Affected Endpoints MRID No. Study Classification

Mallard Duck ( Anas platyrhychos ) 96.5 Avian Reproduction NOAEC: 1060
LOAEC: > 1060 None 467152- 14 Acceptable

Northern Bobwhite ( Colinus virginianus ) 96.5 Avian Reproduction NOAEC: 1060
LOAEC: > 1060 None 468001- 15 Acceptable

iii. Mammals, Acute and Chronic

Wild mammal testing is required on a case-by-ca se basis, depending on the results of lower tier laboratory mammalian studies, intended use pattern and pertinent environmental fate characteristics. In most cases, rat or mouse toxicity values obtained from the Agency's Health Effects Division (HED) substitute for w ild mammal testing. A rat multigenerational study and a rat acute oral toxicity study have been submitted to the Agency. The toxicity values for this study are tabulated below.

Mammalian Toxicity Species

% a.i. Test Type Toxicity Value Affected Endpoints MRID No. Study Classification
Laboratory Rat ( Rattus norvegicus ) Technical Rat Multigenerational Reproduction toxicity 250 ppm Decreased body weights, weight gains, food consumption, and food utilization 468002 -30 Acceptable

Laboratory Rat ( Rattus norvegicus ) Technical Rat Acute Oral Toxicity > 5000 mg/kg No mortality MRID 468002 -30 Acceptable99 iv. Terrestrial Invertebrates

A honey bee acute contact study using the TGAI is required for mandipropamid because its proposed uses may result in honey bee exposure. Results of this test are tabulated below.

Non-target Insect Acute Contact Toxicity

Species % a.i. LD50 (ug/bee) Toxicity Category MRID No. Study Classification

Honey Bee ( Apis mellifera L.) 99 % > 200 ug ai/bee Practically nontoxic 468001-16 Acceptable

The registrant has also submitted two earthworm acute toxicity studies. One of the studies tested the TGAI and the other study tested the mandipropamid degradate, CGA380778. The results of these studies are illustrated in the table below.

Earthworm Acute Toxicity Test Toxicity

Species Chemical % purity LC 50 Toxicity Category MRID No. Study Classification

Earthworms ( Eisenia fetida ) Mandipropamid 99 >1000 mg ai/kg dw of soil. Nontoxic at the highest concentration s tested 468001- 23 Acceptable

Earthworms ( Eisenia fetida ) CGA380778
(Mandipropamid
Degradate) 99 >1000 mg ai/kg dw of soil. Nontoxic at the highest concentration s tested 468001- 22 Acceptable

The above analysis of the results show that mandipropamid is practic ally non-toxic to honey bees and that mandipropamid and its’ degradat e, CGA380778, is nontoxic to earthworms at the highest concentrations teste d. Therefore, it is presumed that the use of mandipropamid will not pose a significant risk to non-target terrestrial invertebrates.100 b. Toxicity to Freshwater Aquatic Animals I. Freshwater Fish, Acute

Two freshwater fish acute toxicity studies using the TGAI are requi red to establish the toxicity of mandipropamid to fish. The preferre d test species are rai nbow trout (a coldwater fish) and bluegill sunfish (a warmwater fish). The registrant has submitted 3 freshwater fish acute toxicity studies. Two of the studies tested the TGAI and one tested, CGA380778. Currently, all of the registrant submitted freshwater fish toxicity studies testing mandipropamid and the mandipropamid degradat e, CGA380778, are deemed invalid. The studies were invalidated because of the failu re of the study authors to take appropriate measures to ensure the test chemical was adequa tely dissolved in the test water. This was indicated by the failure of the measured concentr ations to remain at least 80% of the nominal concentrations, as required by the fish acute toxicity Guideline, 850.1075. Additionally, the test solutions contained undissolved particul ate test material. Th is was an additional indication of the failure to succe ssfully dissolve the test solution. Solubility is defined by the Agency’s Pesticide Registration Rejection Ra te Analysis Document as the amount of chemical retained in the supernatant of a conve ntionally centrifuged sample of test media. Because the test material was not adequately di ssolved, it was not possible to obtain accurate toxicity endpoint values that could be used for risk assessment purposes. Further details regarding these studies are li sted in the table below.101 Freshwater Fish Acute Toxicity

Species Chemical % purity 96- hour LC50 (a.i. ppm) NOAEC (ppm a.i.) Toxicity Category MRID No. Author/ Year Study Classification

Fathead Minnow ( Pimephales promelas ) Mandipropamid
96.1% a.i. > 5.8 4.4 Note 1 Undeterminable
Note 4 468001- 05 Invalid Note 5

Rainbow trout ( Oncorhynchu s mykiss ) Mandipropamid 96.1% a.i. 4.4 1.7 Note 2 Undeterminable
Note 4 468001- 06 Invalid Note 5

Rainbow trout ( Oncorhynchu s mykiss ) CGA380778 > 43 9.3 Note 3 Undeterminable
Note 4 468001- 04 Invalid Note 5

Note 1: The NOAEC value, based on sub-lethal effect s, was 4.4 mg a.i./L. Su b-lethal effects (loss of equilibrium and lethargy) were observed in th e group exposed to 5.8 mg a.i./L of NOA446510 (Mandipropamid). As no sub-lethal quantitative meas urements were taken, the reviewer was unable to determine an EC 50 value.

Note 2: This NOAEC value based on mortality and sub-le thal effects, was 1.7 mg a. i./L. Sub-lethal effects (surfacing, lying on the bottom of the aquarium, loss of equilibrium, lethargy, erratic swimming and morphological deformity) were observed in the groups exposed to mean-measured concentrations 3.1-6.5 mg a.i./L of NOA446510. As no sub-lethal quantitativ e measurements were taken, the reviewer was unable to determine an EC 50 value.

Note 3: This NOAEC is value, based on mortality and sub-lethal effects, was 9.3 mg/L. Sub-lethal effects (quiescence, sounding, dark discoloration, loss of balance, ceased swimming, labored respiration and swollen abdomen) were observed in the groups exposed to 17-43 mg/L of CGA380778. As no sub-lethal quantitative measurements were taken, the reviewer was unable to determine an EC 50 value.

Note 4: Because of the failure of the mean measured concentrations to remain at least 80% of the nominal concentrations, the concentrations in which these effects were observed cannot be validated.

Note 5: The studies were invalidated because of th e failure of the study auth ors to take appropriate measures to ensure the test chemical was adequately dissolved in the test water. This was indicated by the failure of the measured concentrations to remain at least 80% of the nominal concentrations, as required by the fish acute toxicity Guideline, 850.1075.
ii. Fish, Chronic toxicity.

Mandipropamid is mobile and is likely to readily and frequently (due to multiple applications during a growing season) reach surface water bod ies. Thus, a fish chronic toxicity study testing mandipropamid is required. The regi strant has submitted a fish early life-stage102 chronic toxicity study testing the TGAI. The results of the study demonstrated a NOAEC of 0.210 ppm based on growth. The details of th is study are listed in the table below.

Freshwater Fish Chronic Toxicity

Species % ai Chronic Toxicity NOAEC and LOAEC (a.i. ppm) Most sensitive Endpoint Affected MRID No. Author/Year Study Classification

Fathead minnow 96.5 NOAEC: 0.22
LOAEC:
0.47 Length, wet and dry weight 468001-08 Acceptable

iii. Freshwater Invertebrates, Acute

A freshwater aquatic invertebrate toxicity test using the TGAI is requ ired to establish the toxicity of mandipropamid to aquatic invert ebrates. The preferred test species is Daphnia
magna . Results of this test are tabulated below. The registrant has submitted a study testing the TGAI and a study testing the mandipropamid degradate, CGA380778.

Freshwater Invertebrate Acute Toxicity for Mandipropamid and a Mandipropamid degradate, CGA380778

Species Chemical (% purity). 48-hour EC50 (ppm a.i.) NOAEC (ppm a.i.; based on mortality) Toxicity Category MRID No. Study Classification

Waterflea ( Daphnia
magna ) Mandipropamid (96.5 %) 7.1 4.7 Moderately toxic 468001- 50 Acceptable

Waterflea ( Daphnia
magna ) CGA380778 (98%) 54.2 37 Slightly Toxic 468001- 51 Acceptable

Since the EC 50 for the TGAI, mandipropamid, falls in the range of 1 - 10 ppm, mandipropamid is moderately toxic to aquatic invertebrates on an acute basis. Since the EC 50 for the major degradate of mandipropami d, CGA380778 falls in the range of 10 ppm – 100 ppm, CGA380778 is classified as practica lly nontoxic to freshwat er invertebrates.103 iv. Freshwater Invertebrate, Chronic

Mandipropamid is highly mobile and is likely to readily and frequently (due to multiple applications during a growing season) reach surf ace water bodies. Thus , invertebrate chronic toxicity testing mandipropamid is required. The registrant has submitted one freshwater invertebrate chronic toxicity study however the study was deemed invalid. The study was invalid because reproduction of solvent control daphnids was signi ficantly lower than that of negative control daphnids. According to the EPA memo titled, “Interim Policy Guidance for the Use of Dilution-Water (Negative) and Solven t Controls in Statistical Data Analysis for Guideline Aquatic Toxicology Studies”, da ted March 30, 2006, the study exhibiting such results would be invalidated. The detail s of the study are demonstrated below.

Freshwater Invertebrate Chronic Toxicity

Species

% ai Chronic Toxicity NOAEC and LOAEC (a.i. ppm) Most sensitive Endpoint Affected MRID No. Author/Year Study Classification

Daphnia
magna 99 * NOAEC:
< 0.023
LOAEC:
0.023 Reproduction 468001-07 Invalid Note 1

* Note: The reviewer’s analysis showed that reproduction of solvent control daphnids was significantly lower than that of negative control daphnids, which according to the EPA memo titled, “Interim Policy Guidance for the Use of Dilution-Water (Negative) and Solvent Controls in Statistical Data Analysis for Guideline Aquatic Toxicology Studies”, dated March 30, 2006, would result in the INVALID classification of this study.

c. Toxicity to Estuarine/Marine Animals I. Estuarine/Marine Fish, Acute

Mandipropamid usage may occur in some areas associ ated with marine/estua rine habitats. Thus, marine/estuarine fish toxicity data is required. There are two registrant submitted acute toxicity studies testing marine/estuarine fish. However both studies were deemed invalid. The studies were invalidated because of the failure of the study authors to take appropriate measures to ensure the test chemical was adequately dissolved in the test water. This was indicated by the failure of the measured concentrations to remain at least 80% of the nominal concentrations, as required by the fish acute toxicity Guidelin e, 850.1075. Additionally, the test solutions contained undissolved particulate test material. Th is was an additional indication of the failure to successfully dissolve the test so lution. Solubility is define d by the Agency’s Pesticide Registration Rejection Rate Anal ysis Document as the amount of chemical retained in the supernatant of a conventionally cen trifuged sample of test media. Because the test material was not adequately dissolved, it was not possible to ob tain accurate toxicity endpoint values that104 could be used for risk assessment purposes. The de tails of the studies are demonstrated in the table below.

Marine/Estuarine Fish Toxicity for Mandipropamid

Species (% purity) 96-hour LC50 (ppm a.i.) NOAEC (ppm a.i.) Toxicity Category MRID No. Study Classification

Sheepshead minnow ( Cyprinodon variegates ) 96.1 4.5 2.8 Note 1 Undeterminable
*** 468001 -03 Invalid Note 4

Sheepshead minnow ( Cyprinodon variegatus ) 96.1 >5.8 mg a..i./L 4.4 Note 2 Undeterminable
Note 3 468001 -05 Invalid Note 4

Note 1: The NOAEC value, based on mortalit y and sub-lethal effects, was 2.8 mg a.i/L. Sub-lethal effects (erratic swimming, ly ing on the bottom of the test vessel, and surfacing for unusually long periods of time) were obser ved in the groups exposed to 4.3 and 6.1 mg a.i./L of NOA446510. As no sub-lethal quantitative measurements were reported, the reviewer wa s unable to determine an EC 50 value.

Note 2: The NOAEC value, based on sub-lethal effects, was 4.4 mg a.i./L. Sub-lethal effects (loss of equilibrium and lethargy) were observed in the group exposed to 5.8 mg a.i./L of NOA 446510 (Mandipropamid). As no s ub-lethal quantitative measurements were taken, the re viewer was unable to determine an EC 50 value.

Note 3: Because of the failure of the mean measured concentrations to remain at l east 80% of the nominal concentrations, the c oncentrations in which these effects were observed cannot be validated.

Note 4: The studies were invalidated becau se of the failure of the study authors to take appropriate measures to ensure the te st chemical was adequately dissolved in the test water. Th is was indicated by the failure of the measured concentrations to remain at least 80 % of the nominal concentrations, as required by the fish acute toxicity Guideline, 850.1075.

Estuarine and Marine Fish, Chronic

Currently, no estuarine and marine fish chroni c toxicity studies have been submitted to the Agency.

iii. Estuarine and Marine Invertebrates, Acute Mandipropamid usage may occur in some areas associ ated with marine/estua rine habitats. Thus, marine/estuarine fish toxicity data is required. There are two registrant submitted acute toxicity studies testing marine/estuarine in vertebrate. The details of the studies are demonstrated in the table below.105 Freshwater Invertebrate Toxicity for Mandipropamid

Species Chemical (% purity). 96-hour EC50 (ppm a.i.) NOAEC (ppm a.i.;) Toxicity Category MRID No. Study Classification

Mysid shrimp ( Americamysis bahia ) 96.1% 1.7(based

on mortality) 0.58 Moderately toxic 468001 -02 Acceptable

Oyster Crassostrea virginica 96.1 0.91 (based on sublethal effect of shell deposition) 0.46 Very Highly toxic 468001 -01 Acceptable

iv. Estuarine and Marine Invertebrate, Chronic

Currently, no estuarine and marine invertebrate chronic toxicity studies have been submitted to the Agency.
d. Toxicity to Plants

i. Terrestrial Plants

The registrant submitted a seedling emergence and vegetative vigor study testing the A12946B, the formulation containing the active ingredie nt Mandipropamid. The following summarizes the results of both studies.

The effect of A12946B on the seed ling emergence of monocot (corn, Zea mays ; oat, Avena sativa ; onion, Allium cepa ; and ryegrass, Lolium perenne ) and dicot (carrot, Daucus carota ; cucumber, Cucumis sativa ; radish, Raphanus sativus ; soybean, Glycine max ; sugar beet, Beta vulgaris ; and tomato, Lycopersicon esculentum ) crops was studied at nominal application rates of 0 (negative and surfactant contro ls), 0.0413, 0.0825, 0.165, 0.330 and 0.660 lbs ai/A. The growth medium used in the seedling emergence test was natural soil, classified as a loam soil, with an organic matter content of 1.7% (1.0% or ganic carbon) and an adjusted pH of 7.4. On day 21 the surviving plants per po t were recorded and cut at so il level for measuring the plant height and dry weight.

Dry weight was significantly a ffected in cucumber, soybean and tomato, but reductions did not exceed 25%. The % inhibition in seedling emergen ce in the treated species as compared to the control ranged from -4 to 8% . No monocot species was sens itive to treatment, but an EC 05 value could be calculated for corn dry weight. Carrot was the only dicot species to exhibit a reduction of ≥ 25% (based on dry weight) rela tive to the negative control; however, the response was not dose-dependent, with the three lo west treatment groups experiencing increases in dry weight of 2-21%. The reviewer was unable to determine re liable ECx values for carrot dry weight.106 Additionally, one replicate in the highest treatment group failed to emerge and overall emergence of the controls and treatment groups was fairly lo w (60-73%). This implies that factors other than treatment contributed to the poor performance of carrot in this study. The study was deemed supplemental because of this study deficiency.

SEEDLING EMERGENCE STUDY (468001-17) SUMMARY OF MOST SENSITIVE

PARAMETERS BY SPECIES (LBS AI/A). Species Endpoint NOAEC EC 05 EC 25 EC 50 Corn None 0.660 <0.0413 >0.660 >0.660 Oat None 0.660 >0.660 >0.660 >0.660 Onion None 0.660 ND >0.660 >0.660 Ryegrass None 0.660 ND >0.660 >0.660 Carrot Not Determinable Not Determinable Not Determinable Not Determinable Not Determinable Cucumber None 0.165 <0.0413 >0.660 >0.660 Radish None 0.660 0.36 >0.660 >0.660 Soybean None 0.165 <0.0413 >0.660 >0.660 Sugar beet None 0.660 ND >0.660 >0.660 Tomato None 0.660 ND >0.660 >0.660

The effect of A12946B on the vege tative vigor of monocot (corn, Zea mays ; oat, Avena sativa ; onion, Allium cepa ; and ryegrass, Lolium perenne ) and dicot (carrot, Daucus carota ; cucumber, Cucumis sativa ; radish, Raphanus sativus ; soybean, Glycine max ; sugar beet, Beta vulgaris ; and tomato, Lycopersicon esculentum ) crops was studied at nominal a pplication rates of 0 (negative and surfactant controls), 0.0495, 0.0994, 0.198, 0.396 a nd 0.792 lbs ai/A. The growth medium used in the test was an artificial soil that repr esented a loam soil and was composed of a mixture of kaolinite clay, industrial quartz sand and peat; the organi c matter content was 1.7% (1.0% organic carbon) and the pH was 7.4. On day 21 th e surviving plants per pot were recorded and cut at soil level for measuring th e plant height and dry weight.

In the vegetative vigor test, plant height was affected by A12946B treatment in oat only. Dry weight, plant height and survival were not aff ected in any other species. The most sensitive monocot species, based on plant height, in th e vegetative vigor test was oat with an EC 25 of >0.792 lbs ai/A and a NOAEC of 0.198 lbs ai/A. No dicot was sensitive to treatment, so the EC 25 value was >0.792 lbs ai/A and th e NOAEC values was 0.792 lbs ai/A.

The study was deemed acceptable for a tier II vege tative vigor terrestria l plant toxicity study.107 VEGETATIVE VIGOR STUDY (468001-18 ) SUMMARY OF MOST SENSITIVE

PARAMETERS BY SPECIES (LBS AI/A). Species Endpoint NOAEC EC 05 EC 25 EC 50 Corn None 0.792 >0.792 >0.792 >0.792 Oat Plant Height 0.198 >0.792 >0.792 >0.792 Onion None 0.792 >0.792 >0.792 >0.792 Ryegrass None 0.792 >0.792 >0.792 >0.792 Carrot None 0.792 >0.792 >0.792 >0.792 Cucumber None 0.792 >0.792 >0.792 >0.792 Radish None 0.792 >0.792 >0.792 >0.792 Soybean None 0.792 >0.792 >0.792 >0.792 Sugar beet None 0.792 >0.792 >0.792 >0.792 Tomato None 0.792 >0.792 >0.792 >0.792ii. Aquatic Plants

The registrant has submitted a nonvascular aquatic plant toxicity study te sting the effect of mandipropamid on Pseudokirchneriella subcapitata, and a vascular aquatic plant toxicity study testing the effect of mandipropamid on lemna gibba . The registrant has also submitted a nonvascular aquatic plant toxi city study testing the eff ect of CGA380778, a mandipropamid degradate, on Pseudokirchneriella subcapitata . Results of the studies are tabulated below.

Tier II Mandipropamid Aquati c Plant Toxicity Test

Test Species Test Chemical and % purity EC50 (ppm) NOEAL or EC05 (ppm) Endpoint Effected Study Category MRID

Lemna gibba Mandipropamid 96.1 > 7.9 1.3 (EC05) Biomass Acceptable 468001-19 Pseudokirchneriella subcapitata Mandipropamid 96.5 > 2.5 2.5 (NOEAL) Bioma ss Acceptable 468001-21 Pseudokirchneriella subcapitata CGA380778 98.2% 16 2.4 Bi omass Acceptable 468001-20

1

# APPENDIX F. The Risk Quotient Method and Levels of Concern

The risks to terrestrial and a quatic organisms are determined based on a method by which risk quotients (RQs) are compared with levels of concern (LOCs). This method provides an indication of a chemical’s potential to cause an effect in the field from effects observed in laboratory studies, when used as directed. Risk quotients are expressed as the ratio of the estimated environmental concentration (EEC) to the species-specific toxicity reference value (TRV):



# RQ EEC
TRV =

Units for EEC and TRV should be the same (e.g., μg /L or ppb). The RQ is compared to the LOC as part of a risk characterizat ion. Acute and chronic LOCs for te rrestrial and aquatic organisms are given in recent Agency guidance (USEPA 2004) and summarized in Table F-1 below.

Table F-1. Level of concern (LOC) by ri sk presumption category (USEPA 2004) Risk Presumption RQ LOC Mammals and Birds Acute Risk a EEC b /LC 50 or LD 50 /sqft c or LD 50 /day d 0.5 Acute Restricted Use e EEC/LC 50 or LD 50 /sqft or LD 50 /day (or LD 50 <50 mg/kg) 0.2 Acute Endangered Species f EEC/LC 50 or LD 50 /sqft or LD 50 /day 0.1 Chronic Risk EEC/NOEC 1 Aquatic Animals Acute Risk EEC g /LC 50 or EC 50 0.5 Acute Restricted Use EEC/LC 50 or EC 50 0.1 Acute Endangered Species EEC/LC 50 or EC 50 0.05 Chronic Risk EEC/NOEC 1 Terrestrial and Semi-aquatic Plants Acute Risk EEC/EC 25 1 Acute Endangered Species EEC/EC 05 or NOEC 1 Aquatic Plants Acute Risk EEC h /EC 50 1 Acute Endangered Species EEC g /EC 05 or NOEC 1

a Potential for acute toxicity for receptor species if RQ > LOC (USEPA 2004).
b Estimated environmental concentratio n (ppm) on avian/mammalian food items

c mg/ft 2

d mg of toxicant consumed per day

e Potential for acute toxicity for receptor species, even considering restricted use classification, if RQ > LOC (USEPA 2004).
f Potential for acute toxicity for endangered species of receptor species if RQ > LOC (USEPA 2004).

g EEC = ppb or ppm in water
h EEC = lbs a.i./acre

2For acute exposure to terrestrial and aquatic plan ts, an LOC of 1 is used. Currently the Agency does not perform assessments for chronic risk to plants or acute/chroni c risks to non-target insects.

For the Tier II aquatic assessm ent of mandipropamid acute exposure is represented by the maximum 24-hour EEC value calculated using PRZM/EXAMS. EECs used to assess acute and chronic risk to avian and mammalian species to mandipropamid were calculated using the Tier I model T-REX.

The Agency has developed an Endangered Specie s Protection Program to identify pesticides whose use may cause adverse impacts on endangered and threatened species, and to implement mitigation measures that will eliminate the adverse impacts. At present, the program is being implemented on an interim basis as describe d in a Federal Register notice (54 FR 27984–28008, July 3, 1989), and is providing information to pes ticide users to help them protect these species on a voluntary basis. As currently planned, the final program will call for label modifications referring to required limitations on pesticide uses , typically as depicted in county-specific bulletins or by other site-specific mechanisms as specified by state partners. A final program, which may be altered from the interim program, w ill be described in a future Federal Register notice. The Agency is not imposing label modifica tions at this time. Rather, any requirements for product use modifications will oc cur in the future under the Endangered Species Protection Program.

3

# APPENDIX G. Data Requirments

Table G-1. Environmental Fate Data Requirements for Mandipropamid Guideline No. Data Requirement MRID No. Study Classification 161-1 Hydrolysis 4 6800007,8 Acceptable

161-2 Photodegradation in Water (pH 7) 46800009,10,11,12,1 3, 14 Acceptable 161-3 Photodegradation on Soil 4680000 Acceptable 161-4 Photodegradation in Air No Data 162-1 Aerobic Soil Metabo lism 4680020,2 1,22,23,24,25,26, 27,28 Acceptable Supplemental Supplemental Supplemental Supplemental Supplemental Supplemental Supplemental Supplemental 162-2 Anaerobic Soil Metabolism 468000027 Supplemental 162-3 Anaerobic Aquatic Metabo lism 46800033,34 Unacceptable

162-4 Aerobic Aquatic Meta bolism 46800032 Unacceptable

163-1 Adsorption/Desorption 46800035, 36, 37,38, 39,40,41,42, 43 Supplemental

163-2 Laboratory Volatility No Data 163-3 Field Volatility No Data 164-1 Terrestrial Field Di ssipation 46800045 Acceptable 164-2 Aquatic Field Dissipation No Data 164-3 Forestry Dissipation No Data 165-4 Accumulation in Fish No Data 166-1 Ground Water – small prospective No Data 166-2 Ground Water – small retrospective No Data 201-1 Droplet Size Spectrum No Data 202-1 Drift Field Evaluation No Data

4Table G-2. Ecological Effects Data Requirements for Mandipropamid

Guideline No. Data Requirement Species Formulation Are data adequate for ecological risk assessment? MRID Number (Study Classification) Anas Platyrhynchos (mallard duck) Technical Yes 46800110 (Acceptable) 71-1 850.2100 Avian Acute Oral Toxicity Colinus virginianu (bobwhite quail) Technical Yes 46800111 (Acceptable) Colinus virginianu (bobwhite quail) Technical Yes 46800112 (Acceptable) 71-2 850.2200 Avian Subacute Dietary Toxicity Anas Platyrhynchos (mallard duck) Technical Yes 46800113 (Acceptable) Colinus virginianu (bobwhite quail) Technical Yes 46800114 (Acceptable) 71-4 850.2300 Avian Reproduction Toxicity Anas Platyrhynchos (mallard duck) Technical Yes 46800115 (Acceptable)

Pimephales promelas (fathead minnow) Technical No 46800104 (Unacceptable) 72-1 850.1075 Freshwater Fish LC 50 Oncorhynchus mykiss (rainbow trout) Technical No 46800105 (Unacceptable)

72-2 850.1010 Freshwater Invertebrate Acute LC 50 Daphnia magna (water flea) Technical Yes 46800150 (Acceptable)

72-3(a) 850.1075 Estuarine/Marine Fish LC 50 Cyprinodon variegatus (sheepshead minnow) Technical No 46800101 (Unacceptable)

72-3(b) 850.1025 Estuarine/Marine Invertebrate (Mollusk) Crassostrea virginica (eastern oyster) Technical Yes 46800101 (Acceptable)

72-3(c) 850.1035 850.1045 Estuarine/Marine Invertebrate (Mysid) Americamysis bahia (mysid shrimp) Technical Yes 46800102 (Acceptable)

72-4 (a) 850.1400 Fish Early Life-Stage (Freshwater) (Marine) Pimephales promelas (fathead minnow) Technical Yes 46800108 (Acceptable)

72-4 (b) 850.1300 850.1350 Aquatic Invertebrate Life-Cycle (Freshwater) (Marine) Americamysis bahia (mysid shrimp) Technical No data submitted

5Table G-2. Ecological Effects Data Requirements for Mandipropamid

Guideline No. Data Requirement Species Are data

Formulation adequate for MRID Number ecological risk (Study assessment? Classification) 72-5 850.1500 Fish Full LifeCycle (Freshwater) (Marine) No data submitted No data submitted No –

122-1(a) 850.4100 Seed Germination/ Seedling Emergence (Tier I) No data submitted No data submitted No –

122-1(b) 850.4150 Vegetative Vigor (Tier I) No data submitted No data submitted No –

Technical Yes 122-2 850.4400 Aquatic Plant Growth (Tier I) Lemna gibba (duckweed) Technical Yes 123-1(a) 850.4225 Seed Germination/ Seedling Emergence (Tier II) Monocots and Dicots Formulation c Partially 46800117 (Supplemental)

123-1(b) 850.4250 Vegetative Vigor (Tier II) Monocots and Dicots Formulation c Yes 46800118 (Acceptable) 123-2 850.4400 Aquatic Plant Growth (Tier II) Lemna gibba (duckweed) Technical Yes 466800119 (Acceptable) Anabaena flos-aquae (freshwater alga) Technical No

Skeletonema costatum (marine alga) Technical No

Pseudokirchneriella subcapitata Technical Yes 46800121 (Acceptable) 123-2 850.5400 Algal Plant Toxicity (Tier I and Tier II)

Navicula pelliculosa (freshwater alga) Technical No

141-1 850.3020 Honeybee Acute Contact Toxicity Test Apis mellifera (honey bee) Technical Yes 46800116 (Supplemental)

141-2 850.3030 Residues on Foliage Honeybee Toxicity Test No data submitted No data submitted No

NonGuideline Honeybee Feeding Toxicity Test No Data Submitted No data submitted No

NonGuideline Benthic Organisms Chironomus riparius (midge) No data submitted No

NonGuideline Earthworm Subacute No No data submitted No

6

# APPENDIX H. Use Characterization Maps

There are no madnipropamid use ch aracterization maps available.

7

# APPENDIX I. Environmental Fate Bibliography

MRID Environmental Fate Studies Submitted to EPA

MRID 46800007 - Buckel, T. 2002. Hydrolysis of [ethyl-1- 14 C]-labelled NOA446510 under laboratory conditions. Unpub lished study performed and sponsored by Syngenta Crop Protection AG, Basel, Switzerland, and s ubmitted by Syngenta Crop Protection, Inc. Greensboro, NC. Basel No.: 02TB01; Syngenta No.: T004591-02. Experiment started April 2, 2002, and completed May 13, 2002. Final report issued November 8, 2002.

MRID 46800008 - Murphy, T. 2006. Hydrolysis of [ethyl-1- 14 C]-labelled NOA446510 under laboratory conditions, study profile. Unpublis hed study summary prepared, sponsored and submitted by Syngenta Crop Protection, Inc., Green sboro, North Carolina. Syngenta Study No.: T004591-02. Experimental start and termination dates not applicable. Final report issued February 24, 2006.

MRID 46800009- Kuet, S.F. 2004. NOA446510: photolysis of 14 C-chlorophenyl ring labelled NOA446510 in sterile natural wa ter under laboratory conditions. Unpublished study performed by Jealott’s Hill International Research Centre, Berkshire, UK, and submitted and sponsored by Syngenta Crop Protection, Inc. Greensboro, NC. Jealott’s Hill No.: RJ3510B; Syngenta No.: T004575-02. Experiment started October 2, 200 3, and completed January 20, 2004. Final report issued November 25, 2004.

MRID 46800010- Harrison, C.L. 2004. NOA446510: 14 C-methoxyphenyl labelled sterile natural water photolysis under la boratory conditions. Unpublishe d study performed by Jealott’s Hill International Research Centre, Berkshire, UK, and submitted and sponsored by Syngenta Crop Protection, Inc. Greensboro, NC. Jealott’ s Hill No.: RJ3481B; Syngenta No.: T004607-02. Experiment started November 27, 2003, and co mpleted March 22, 2004. Final report issued December 22, 2004.

MRID 46800011 - Nicollier, G. 2003. Aqueous photolysis of [chlorophenyl-U- 14 C]-labelled NOA446510 under laboratory condi tions. Unpublished study performed and sponsored by Syngenta Crop Protection AG, Basel, Switzerla nd, and submitted by S yngenta Crop Protection, Inc. Greensboro, NC. Basel No.: 02GN07; Synge nta No.: T004618-02. Experiment started May 14, 2002, and completed July 01, 2003. Final report issued October 31, 2003.

MRID 46800012 - Murphy, T. 2006. Aqueous photolysis of [chlorophenyl-U- 14 C]-labelled NOA446510 under laboratory condi tions, study profile. Unpublished study summary prepared, sponsored and submitted by Syngenta Crop Protec tion, Inc., Greensboro, North Carolina. Syngenta Study No.: T004618-02. Experimental star t and termination dates not applicable. Final report issued February 23, 2006.

MRID 46800013 - Hand, L.H. and J. Towers. 2003. Aqueous photolysis of 14 C-methoxyphenylNOA446510 under laboratory condi tions. Unpublished study performed and sponsored by

8Syngenta Jealott’s Hill Interna tional Research Centre, Berkshire, UK and submitted by Syngenta Crop Protection, Inc., Greensboro, NC. St udy No.: 02JH091; Syngenta No.: T004630-02. Experiment started November 20, 2002, and co mpleted May 28, 2003. Final report issued August 18, 2003.

MRID 46800014 - Murphy, T. 2006. Aqueous photolysis of 14 C–methoxypehnyl-NOA446510 under laboratory conditions, study profile. Unpublished study summa ry prepared, sponsored and submitted by Syngenta Crop Protection, Inc., Green sboro, North Carolina. Syngenta Study No.: T004630-02. Experimental start and termination dates not applicable. Final report issued February 13, 2006.

MRID 46800015 - Bramley, Y.M. NOA446510: Soil photolysis of 14 C-chlorophenyl ring labelled NOA446510 under laboratory conditions. Unpublished study performed by Jealott’s Hill International Research Centre, Berkshire, UK and sponsored and submitted by Syngenta Crop Protection, Inc., Greensboro, NC. Re port No.: RJ3535B. Syngenta No.: T008105-03. Experiment initiated January 14, 2004 and comp leted January 7, 2005. Final report issued February 7, 2005.

MRID 46800016 : Murphy, T. 2006. NOA446510: Soil photolysis of 14 C-methoxyphenyl ring labelled NOA446510 under laboratory conditions. Unpublished study sponsored and submitted by Syngenta Crop Protection, Inc ., Greensboro, NC. Syngenta N o.: T004595-02. Experiment start and completion date not applicable . Final report issu ed February 13, 2006.

9MRID 46800017 : Kuet, S.F. 2003. NOA446510: Soil photolysis of 14 C-methoxyphenyl ring labelled NOA446510 under laboratory conditions. Unpublished study performed by Jealott’s Hill International Research Centre, Berkshire, UK and sponsored and submitted by Syngenta Crop Protection, Inc., Greensboro, NC. Jealot t’s Hill No.: RJ3400B. Syngenta No.: T004595- 02. Study started January 8, 2003 and comple ted August 20, 2003. Final report issued December 10, 2003.

MRID 46800016 : Murphy, T. 2006. NOA446510: Soil photolysis of 14 C-methoxyphenyl ring labelled NOA446510 under laboratory conditions. Unpublished study sponsored and submitted by Syngenta Crop Protection, Inc ., Greensboro, NC. Syngenta N o.: T004595-02. Experiment start and completion date not applicable . Final report issu ed February 13, 2006.

MRID 46800018 : McKillican, C. B. 2005. Photodegradation of 14 C-NOA-446510 on soil under artificial light. Unpublished study perfor med, sponsored and submitted by Syngenta Crop Protection, Inc., Greensboro, NC. Syngenta No.: 737-02. Study started June 15, 2004 and completion date not reported . Final report issued July 29, 2005.

MRID 46800019 : Murphy, T. 2006. Photodegradation of 14 C-NOA-446510 on soil under artificial light. Unpublished study sponsored and submitted by Syngenta Crop Protection, Inc., Greensboro, NC. Syngenta No.: 000737-02. Experiment start and completion date not applicable. Final report issued February 13, 2006.

MRID 46800020 : Clark, A. 2004. Metabolism of [ 14 C-chlorophenyl]-NOA-446510 in viable soil under aerobic conditions. Unpublished study performed, submitted and sponsored by Syngenta Crop Protection, Inc, Greensboro, NC . Study No.: T000680-02. Syngenta No.: 680- 02. Experiment started March 7, 2003. Experiment al completion date not reported. Final report issued September 1, 2004.

MRID 46800021 : Murphy, T. 2006. Metabolism of [ 14 C-chlorophenyl]-NOA-446510 in viable soil under aerobic conditions. Unpublished study submitted and sponsored by Syngenta Crop Protection, Inc, Greensboro, NC. Syngenta No.: T000680-02. Experiment start and completion date not applicable. Final report issued February 13, 2006.

MRID 46800022 : Nicollier, G. 2003. Me tabolism of [methoxyphenyl-U- 14 C] labelled NOA446510 under aerobic, aerobic/anaerobic and sterile aerobic laboratory conditions in one soil at 20 ° C. Unpublished study performed by Sy ngenta Crop Protection AG, Basel, Switzerland, and submitted and sponsored by Sy ngenta Crop Protection, Inc., Greensboro, NC. Basel Number: 02RF02. Syngenta Number: T 004633-02. Experiment initiated on June 6, 2002 and completed on November 28, 2003. Final report issued on December 18, 2003.

MRID 46800023: Berdat, T. 2005. Rate of degradation of [ 14 C] CGA380778 (metabolite of NOA446510) in various soils under aer obic laboratory conditions at 20 ° C. Unpublished study performed and sponsored by Syngenta Crop Prot ection AG, Basel, Switzerland and submitted by Syngenta Crop Protection, Inc., Greensboro, NC. Sygenta No.: T004943-04. Experiment started August 4, 2004 and completed January 20, 2005. Final report issued March 13, 2005.

10MRID 46800024 : Hand, L.H. 2004. NOA446510: Rate of degradation in one soil under various laboratory conditions. Unpublished st udy performed by Jealott’s Hill International Research Centre, Berkshire, UK and submitted and sponsored by Syngenta Crop Protection, Inc, Greensboro, NC. Report No.: RJ3487B. Syngenta No.: T008097-03. Experiment started July 7, 2003 and completed February 27, 2004. Final report issued July 14, 2004.

MRID 46800025 : Murphy, T. 2006. NOA446510: Rate of degradation in one soil under various laboratory conditions. Unpublished study submitted and sponsored by Syngenta Crop Protection, Inc., Greensboro, NC. Syngenta No.: T008097-03. Experiment start and completion date not applicable. Final report issued February 13, 2006.

MRID 46800026 : Dorn, R., A. Clark, J. Perine, W. Chen, and T. Murphy. 2006. Evaluation of degradation times after adjustment for temper ature and moisture effects of NOA446510 and its metabolite in various soils under laboratory c onditions. Unpublished summary report prepared, sponsored and submitted by Syngenta Crop Protec tion, Inc., Greensboro, North Carolina. Syngenta Study No.: T014422-05. Experimental start date and termination da te not applicable. Final report issued March 1, 2006.

MRID 46800027 : Nicollier, G. 2003. Me tabolism of [chlorophenyl-U- 14 C] labelled NOA446510 under aerobic and aero bic/anaerobic laboratory c onditions in one soil at 20 ° C. Unpublished study performed by Syngenta Crop Protection AG, Basel, Switzerland, submitted and sponsored by Syngenta Crop Protection, Inc. , Greensboro, NC. Basel Number: 02TB03; Syngenta Number: T004572-02. Experiment initiated on July 16, 2002 and completed on January 7, 2003 (p. 9). Final report issued on November 6, 2003.

MRID 46800028 : Kuet, S.F. NOA446510: Metabolis m and rate of degradation of 14 Cchlorophenyl ring labelled NOA4465 10 under aerobic laboratory c onditions, in three soils, at 20 ° C. Unpublished study performed by Jealott’s H ill International Research Centre, Berkshire, UK and submitted and sponsored by Syngenta Cr op Protection, Inc, Greensboro, NC. Report No.: RJ3469B. Syngenta No.: T008109-03. Expe riment started March 27, 2003 and completed December 3, 2003 (p. 28). Final report issued July 16, 2004.

MRID 46800029 : Dorn, R. 2005. Evaluation of half-lives of selected metabolites of NOA446510 in aquatic systems. Unpublished summary report prepared, sponsored and submitted by Syngenta Crop Protection, Inc., Green sboro, North Carolina. Syngenta Study No.: T001209-06 and Report No.: Ass05RD04 (pp. 1, 4). Experimental start date and termination date not applicable. Fina l report issued August 16, 2005.

MRID 46800030: Murphy, T. 2006. NOA446510: degradat ion in two aquatic sediment systems, study profile. Unpublished study su mmary prepared, sponsored and submitted by Syngenta Crop Protection, Inc., Greensboro, Nort h Carolina. Syngenta Study No.: T008095-03. Experimental start and termination dates not applicable. Final report issued March 9, 2006.

11MRID 46800031: Hurt, A.D. 2005. NOA446510: degrad ation on two aquatic sediment systems, final report. Unpublished study perfor med by Jealott's Hill International Research Centre, Berkshire, United, Kingdom, sponsored and submitted by Syngenta Crop Protection, Inc., Greensboro, North Carolina. JH Study No.: 03JH023 and Report No.: RJ3669B (pp. 1, 15 in MRID 46800031). Syngenta Study No.: T008095- 03. Experimental start date July 16, 2003, and termination date February 24, 2005 (p. 50 in MRID 4600031). Final report issued July 27, 2005.

MRID 46800032 : Oliver, R.G., et al . 2005. NOA446510: degradation in an outdoor aquatic sediment system. Unpublished study performed by Jealott's Hill International Research Centre, Berkshire, United Kingdom, sponsored and submitted by Syngenta Crop Protection, Inc., Greensboro, North Carolina. JH Study No.: 04JH007 and Report No.: RJ3569B (pp. 1, 12). Syngenta Study No.: T009117-04. Experimental start date June 2, 2004, and termination date May 10, 2005 (p. 35). Final re port issued July 27, 2005.

MRID 46800033: Hurt, A.D. 2005. NOA446510: degradati on in two aquatic sediment systems (methoxyphenyl ring), final report. Unpublished st udy performed by Jealott's Hill International Research Centre, Berkshire, United Kingdo m, sponsored and submitted by Syngenta Crop Protection, Inc., Greensboro, North Carolina. JH Study No.: 03JH035 and Report No.: RJ3580B (pp. 1, 6 in MRID 46800033). Syngenta Study No.: T008104-03. Experimental start date May 6, 2004, and termination date April 13, 2005 (p. 43 in MRID 4600033). Final report issued July 14, 2005.

MRID 46800034: Clark, A. 2006. NOA446510: degradati on on two aquatic sediment systems (methoxyphenyl ring), study profile. Unpublishe d study summary prepared, sponsored and submitted by Syngenta Crop Protection, Inc., Green sboro, North Carolina. Syngenta Study No.: T008104-03. Experimental start and termination date s not applicable. Fina l report issued March 3, 2006.

MRID 46800035 : Indergand, P. 2005. Adsorption/desorption of a [chlorophenyl-U- 14 C]- labeled SYN521195 in various soils. Unpublished study performed and sponsored by Syngenta Crop Protection AG, Bracknell, Basel, Switzerla nd; submitted by Syngenta Crop Protection Inc., Greensboro, North Carolina. Syngenta Number T013384-04. Experimental start date January 27, 2005, and experimental completion date June 21, 2005 (p. 9). Study completion date August 19, 2005.

MRID 46800036 : Hand, L.H. and E.A. Fleming. 2005. Adsorption/desorption properties of a metabolite (SYN539678) in three soils. U npublished study performed by Jealott’s Hill International Research Centre, Bracknell, Berkshire, United Kingdom; submitted and sponsored by Syngenta Crop Protection Inc., Greensboro, No rth Carolina. Syngenta Number T013385-04. Jealott’s Hill Number RJ3674B. Experimental start date January 11, 2005, and experimental completion date May 11, 2005 (p. 22). Study completion date July 6, 2005.

MRID 46800037 : Indergand, P. and G. Nicollier. 2005. Adsorption/desorption of [phenyl-U14 C]-labeled SYN500003 in various soils (including final report amendment 1). Unpublished

12study performed and sponsored by Syngenta Crop Protection AG, Basel, Switzerland; submitted by Syngenta Crop Protection Inc., Greensboro, No rth Carolina. Syngenta Number T0006595-04. Experimental start date January 11, 2005, and expe rimental completion date May 2, 2005 (p. 9). Study completion date June 9, 2005.

MRID 46800038: Nicollier, G. 2003. Adsorp tion/desorption of [methoxyphenyl-U- 14 C]- labelled NOA446510 in various soils (including final report amendment 1). Unpublished study performed and sponsored by Syngenta Crop Protection AG, Basel, Switzerland; and submitted by Syngenta Crop Protection Inc., Greensboro, NC. Syngenta AG Study Number T004577-02. Basel Number 02TB04. Experimental start da te August 9, 2002, and completion date February 18, 2002 (p. 9). Final repor t issued October 24, 2003.

MRID 46800039: Murphy, T. 2006. Adsorption/ desorption of [methoxyphenyl-U- 14 C]-labelled NOA446510 in various soils. Unpublished st udy submitted and sponsored by Syngenta Crop Protection Inc., Greensboro, NC. Syngenta St udy Number T004577-02. Study completion date February 27, 2006.

MRID 46800040: Berdat, T. and G. Nicollier. 2004. NOA446510: Adsorption/desorption of [methoxyphenyl-U- 14 C]-labelled NOA446510 in various US fi eld soils (includes final report amendment 1). Unpublished study performed by Syngenta Crop Protection AG, Basel, Switzerland; sponsored and submitted by Syngent a Crop Protection Inc., Greensboro, North Carolina. Study Number 04TB01. Syngenta Number T000738-02. Experimental start date January 16, 2004, and experimental completion date March 17, 2004 (p. 9). Study completion date December 23, 2004.

MRID 46800041: Murphy, T. 2006. NOA446510: Adso rption/desorption of [methoxyphenylU- 14 C]-labelled NOA446510 in various US field soils. Sponsored and submitted by Syngenta Crop Protection Inc., Greensboro, North Carolin a. Syngenta Number T000738-02. Completion date March 8, 2006.

MRID 46800042: Adam, D. 2004. Adsorption/desorption of [ 14 C]-CGA380778 on various soils. Unpublished study performed by RCC Ltd, Itingen, Switzerland; sponsored and submitted by Syngenta Crop Protection Inc., Greensboro, North Carolina. RCC Study Number 855381. Syngenta Number T004956-04. Experimental star t date August 11, 2004, and completion date September 22, 2004 (p. 12). Study completion date December 6, 2004.

MRID 46800043: Murphy, T. 2006. Adsorption/desorption of [ 14 C]-CGA380778 on various soils. Sponsored and submitted by Syngenta Crop Protection Inc., Greensboro, North Carolina. Syngenta Number T004956-04. Study completion date March 8, 2006.

MRID 46800044: Harrison, C.L. 2005. NOA446510: Adsorption/desorption properties of a water sediment metabolite SYN504851 in three so ils. Unpublished study pe rformed by Jealott’s Hill International Research Centre, Brackne ll, Berkshire, United Kingdom; submitted and sponsored by Syngenta Crop Protection Inc., Gr eensboro, North Carolina. Syngenta Number

13T013383-04. Jealott’s Hill Number RJ3633B. Expe rimental start date January 5, 2005, and experimental completion date April 1, 2005 (p. 20). Study completion date May 19, 2005.

MRID 46800045: Peters, J. 2005. Dissipation of NOA446510 250SC in bare soil plot under simulated leafy vegetable production conditions in the San Joaquin Valley of California. Unpublished study performed by Syngenta Cr op Protection, Inc., Greensboro, NC; Excel Research Services, Inc., Fresno, CA (field resear ch facility); and North Coast Laboratories, Ltd., Arcata, CA (analytical laborat ory); and sponsored and submitt ed by Syngenta Crop Protection, Inc., Greensboro, NC. Syngenta No. T 000052-03. Excel Study No. ERS23039. NCL No. 110.025. Experiment initiation October 1, 2003 (firs t application date; Appendix 1, p. 84) and completion April 29, 2005 (analytical phase term ination date; Appendix 2, p. 133). Final report issued October 3, 2005.

MRID 46800046: Peters, J. 2005. Dissipation of NOA 446510 250SC under field conditions on crop (potatoes) and bare soil in New Yor k. Unpublished study performed by Syngenta Crop Protection, Inc., Greensboro, NC; Waterborne Environmental, Inc., Leesburg, VA (field phase management); A.C.D.S. Research , Inc., North Ro se, NY (field research facility); and EnviroTest Laboratories, Edmonton, Alberta, Canada (analytical laboratory); and sponsored and submitted by Syngenta Crop Protection, Inc., Greensboro, NC. Syngenta No. T000053-03. ETL Report No. 05SYN150.REP. WEI Study No. 242.68. E xperiment initiation August 7, 2003 (first application date; Appendix 1, p. 93) and co mpletion February 24, 2005 (analytical phase termination date; Appendix 2, p. 199). Final report issu ed October 3, 2005.

MRID 46800047: Peters, J. 2005. Dissipation of NOA446510 250SC in a bare soil plot under simulated squash production conditions in Georgia. Unpublished study performed by Syngenta Crop Protection, Inc., Greensboro, NC (analytical la boratory); Waterborne Environmental, Inc., Leesburg, VA (field management); Ag. Research Associates, LLC, Chula, GA (field research facility); and sponsored and submitted by S yngenta Crop Protection, Inc., Greensboro, NC. Syngenta No. T000054-03. WEI Study No. 242.69. Expe riment initiation May 21, 2003 (first application date; Appendix 1, p. 78) and comple tion July 13, 2005 (analyti cal phase; Appendix 2, p. 165). Final report issued October 3, 2005.

MRID 46800109: Roberts, G.C. and F. Peurou. 2003. NOA446510: Determination of the accumulation and elimination of [ 14 C]NOA446510 in fathead minnow ( Pimephales promelas)

. Unpublished study performed by Brixham Envi ronmental Laboratory, United Kingdom; sponsored and submitted by Syngenta Crop Protecti on, Inc., Greensboro, NC . Brixham Number BL7579/B. Syngenta Number T011831-05. E xperiment initiated March 12, 2003, and completed May 30, 2003 (p. 10). Final report issued December 18, 2003.

14MRID 46800048 (NG study): Peters, J. and B. Schwartz. 2005. Stability of NOA-446510 and CGA-380778 in soil under freezer storage c onditions. Unpublished study performed and sponsored and submitted by Syngenta Crop Prot ection, Inc., Greensbor o, NC. Syngenta No. T001672-03. Experiment initiation November 24, 2003 and completion September 9, 2005 (p. 8 and Appendix 1, p. 68). Final re port issued November 7, 2005.

MRID 46800049 (NG study): Chen, W. 2006. Degradation of NOA446510 influenced by soil temperature under cropped and bare soil conditions: A conceptual m odel approach to bridge data from laboratory to field. Unpublished summary report prepared, sponsored, and submitted by Syngenta Crop Protection, Inc., Greensboro, No rth Carolina. Syngenta Study No.: T021955-04. Experimental start date and termination date not applicable. Final re port issued March 22, 2006.

MRID 46800124 (NG study): Kendall, T. and W. Nixon. 2005. Analytical method verification for the determination of NOA446510 in saltwater. Unpublished study performed by Wildlife International, Ltd., Easton, Maryla nd, sponsored and submitted by Syngenta Crop Protection, Inc., Greensboro, North Carolina. W ildlife International Project No.: 528C-123 (p. 8). Syngenta Study No.: T003405-03. Experimental start and terminatio n date November 15, 2004 (p. 8). Final report issued May 13, 2005.

MRID 46800125 (NG study): Bruns, G. and S. Nelson. 2004. Independent laboratory validation: Syngenta: “Analytical met hod REM 202.02 for the determination of NOA-446510 and its metabolite CGA-380778, in soil, using liq uid chromatography-electrospray ionization tandem mass spectrometry (including valida tion data).” Unpublishe d study performed by Enviro-Test Laboratories, Edmonton, Alberta, Canada, sponsored and submitted by Syngenta Crop Protection, Inc., Greensboro, North Caro lina. ETL Study No.: 04ILV05SYN and Report No.: 04SYN142.REP. Syngenta Study No.: T006443- 04. Experimental start and termination dates not reported; study initiati on date September 17, 2004 (p. 8). Final report issued November 23, 2004.

MRID 46800126 (NG study ): Williams, R. 2003. Analytical method REM 202.02 for the determination of NOA-446510 and its meta bolite CGA-380778, in soil, using liquid chromatography-electrospray io nization tandem mass spectrometry (including validation data). Unpublished study performed, sponsored and su bmitted by Syngenta Crop Protection, Inc., Greensboro, North Carolina. Syngenta Study N o.: T000056-03. Experime ntal start date not reported; study initiation date August 11, 2003 (p. 8). Experimental termination date September 9, 2003 (p. 8). Final report issued October 9, 2003.

15

# APPENDIX J. Ecological Toxicity Bibliography

MRID Ecotoxicity Studies Submitted to EPA

MRID 468001-01 Palmer, S.J., et al., NOA446510: A 96-Hour Flow-Through Shell Deposition Test with the Eastern Oyst er (Crassostrea virginica) Study Completion Date: May 9, 2005 Wildlife International, Ltd., Easton, MD Syngenta Crop Protection, Greensboro, NC

MRID 468001-02 Palmer, Susan J., et al. NOA 446510: A 96-Hour Flow-Through Acute Toxicity Test with the Saltwater Mysi d (Americamysis bahia) May 10, 2005 Wildlife International, Ltd., Easton, MD Sponsor: S yngenta Crop Protection, In c., Greensboro, NC Laboratory Report ID: 5 28A-137 MRID No.:468001-02

MRID 468001-03 Palmer, Susan J., et al. 2005. NOA 446510: A 96-Hour Flow-Through Acute Toxicity Test with the Sheepshead Minnow (Cyprinodon variegatus). Unpublished study performed by Wildlife Internati onal, Inc., Easton, MD. Labor atory report number 528A-138. Study sponsored by Syngenta Crop Protection, In c., Greensboro, NC. Study completed May 9, 2005.

MRID 468001-04 Maynard, S.J. and R.H. Swarbr ick. 2005. NOA446510 Metabolite (CGA380778): Acute Toxicity to Rainbow Tr out (Oncorhynchus mykiss). Unpublished study performed by Brixham Environmental Laborator y, Brixham, Devon TQ5 8BA, UK. Laboratory number BL7958/B. Study sponsored by Syngent a Crop Protection, Inc. Study completed January 4, 2005.

MRID 468001-05 Palmer, S.J., et al. 2006. NOA 446510: A 96-Hour Flow-Through Acute Toxicity Test with the Fathead Minnow (Pimephales promelas). Unpublished study performed by Wildlife International, Lt d., Easton, MD. Laboratory report number 528A-146. Stud sponsored by Syngenta Crop Protection, Inc., Greensboro, NC. Study completed March 7, 2006.

MRID 468001-06 Palmer, S.J., et al. 2006. NOA 446510: A 96-Hour Flow-Through Acute Toxicity Test with the Rainbow Trout (Oncorhy nchus mykiss). Unpublished study performed by Wildlife International, Inc., Easton, MD. La boratory report number 528A-147. Study sponsored by Syngenta Crop Protection, Inc., Greens boro, NC. Study completed March 7, 2006.

MRID 468001-07 Grade, R. 2003. Daphnia magna Reproduction Test: Effects of NOA 446510 on the Reproduction of the Cladoceran Daphnia magna STRAUS in a Semi-Static Laboratory Test. Unpublished study performed by Ecological Sciences, Basel, Switzerland. Laboratory Study No. 2013604. Study sponsored by Syngenta Crop Protection, Inc., Greensboro, NC. Study initiated July 31, 2001 and submitted March 24, 2003.

MRID 468001-08 Maynard, S.J. 2003. NOA 446510 tech: Ea rly-Life Stage Toxicity Test to the Fathead Minnow (Pimephales promelas). Unpublished study performed by Brixham

16Environmental Laboratory, Devon, UK. Laborat ory Project No. BL7577/B. Study submitted by Syngenta Crop Protection, Inc., Greensboro, NC . Study initiated May 12, 2003 and submitted December 22, 2003.

MRID 468001-09 Gallagher, S.P., L.R. Mitchell, and J.B. Beavers. 2002. NOA446510 (AMS): An Acute Oral Toxicity Study w ith the Northern Bobwhite. Unpublished study performed by Wildlife Interna tional Ltd., Easton, MD. Labor atory Project No. 528-141. Study submitted by Syngenta Crop Protection, Inc., Green sboro, NC. Study initiated May 15, 2002 and submitted December 11, 2002.

MRID 468001-10 Gallagher, S.P., and J.B. Beavers. 2005. NOA446510 (AMS): An Acute Oral Toxicity Study with the Mallard. Unpublished study perform ed by Wildlife International Ltd., Easton, MD. Laboratory Project No. 528-142. Study submitted by Syngenta Crop Protection, Inc., Greensboro, NC. Study init iated May 15, 2002 and submitted July 18, 2005.

MRID 468001-11 Gallagher, S.P., et al. 2002. NOA446510 (AMS): A Dietary LC50 Study with the Mallard. Unpublished study performed by Wildlife Internationa l, Ltd., Easton, MD. Laboratory Project No. 528-140. Study subm itted by Syngenta Crop Protection, Inc., Greensboro, NC. Study initiated May 15, 2002 and submitted December 12, 2002.

MRID 468001-12 Gallagher, S.P., et al. 2002. NOA446510 (AMS): A Dietary LC50 Study with the Northern Bobwhite.

MRID 468001-13 Gallagher, S.P., et al. 2002. NOA446510 (AMS): A Dietary LC50 Study with the Northern Bobwhite. Unpublished st udy performed by Wildlif e International, Ltd., Easton, MD. Laboratory Project No. 528-139. Study submitted by Syngenta Crop Protection, Inc., Greensboro, NC. Study initiated May 15, 2002 and submitted December 11, 2002.

MRID 468001-14 Frey, L.T., et al. 2003. NOA446510 (A MS): A Reproduction Study with the Mallard. Unpublished study perf ormed by Wildlife Internationa l Ltd., Easton, MD. Laboratory Project No. 528-150. Study submitted by Syngenta Crop Protection, Inc., Greensboro, NC. Study initiated August 12, 2002 and submitted June 13, 2003.

MRID 468001-15 Frey, L.T., et al. 2003. NOA446510 (A MS): A Reproduction Study with the Northern Bobwhite. Unpublished study performe d by Wildlife International Ltd., Easton, MD. Laboratory Project No. 528-149. Study subm itted by Syngenta Crop Protection, Inc., Greensboro, NC. Study initiated Augus t 12, 2002 and submitted June 13, 2003.

MRID 468001-16 Dr. C. Grimm, Acute Contact and Oral Toxicity of NOA446510 to Honey Bees (Apis mellifera L.) June 03, 2002 Laborator y: Syngenta Crop Protection AG, Ecological Sciences, CH-4002 Basel, Switzerland Syngent a Crop Protection, Greensboro, NC Laboratory Report ID:2013603 (Basel); T011807-05 (Syngenta)

MRID 468001-17 Porch, John R., et al. 2005. NOA446510: A Glasshouse Toxicity Study to Determine the Effects of a 250 g ai/Litre SC Formulation (A12946B) on the Seedling Emergence of Ten Species of Plants. Unpublished study perf ormed by Wildlife Intern ational, Ltd., Easton, MD. Laboratory report number 528-192. Study sponsored by Syngenta Crop Protection, Inc., Greensboro, NC. Study completed October 21, 2005.

1718 MRID 468001-18 Porch, John R., W. Krip and H.O. Krueger. 2005. NOA446510: A Glasshouse Toxicity Study to Determine the E ffects of a 250 g ai/Litre SC Formulation (A12946B) on the Vegetative Vigor on Ten Species of Plants. Unpublished study performed by Wildlife International, Ltd., Easton, MD. Labor atory report number 528- 193. Study sponsored by Syngenta Crop Protection, Inc., Greens boro, NC. Study completed August 12, 2005.

MRID 468001-19 Desjardins, D., et al. 2006. NOA446510: A 7-Day Static-Renewal Toxicity Test with Duckweed (Lemna gibba G3). Unpublished study performed by Wildlife International, Ltd., Easton, MD. Laborator y report number 528A-148. Study sponsored by Syngenta Crop Protection, Inc., Greens boro, NC. Study completed March 7, 2006.

MRID 468001-20 Maynard, S.J. and R.H. Swarbrick. 2005. NOA446510 Metabolite (CGA380778): Toxicity to the Green Alga Pseudokirchneriella subcapitata (Formerly Selenastrum capricornutum ). Unpublished study performed by Brixham Environmental Laboratory, UK. Laboratory re port number BL7960/B. Study sponsored by Syngenta Crop Protection, Inc., Greensboro, NC. Study completed on January 4, 2005.

MRID 468001-21 Volz, Ernst. 2005. Mandiprop amid (NOA446510): Toxicity to Pseudokirchneriella subcapitata (formerly Selenastrum capricornutum) in a 96-hour Algal Growth Inhibition Test. Unpublished study performed by Environmental Chemistry and Pharmanalytics, RCC Ltd., Switzerland. Laborat ory study number A33175. Study sponsored by Syngenta Crop Protection, Inc., Greensboro, NC. Study completed December 15, 2005.

MRID 468001-22 Friedrich, Sabine. 2004. CGA380778 (Metabolite of NOA446510): Acute Toxicity to the Earthworm Eisenia fetida. Unpublished study performed by BioChem agrar, Laboratory for Biological and Chemical Analysis , Ltd., Germany. Laborat ory report number 04 10 48 068. Study sponsored by Syngenta Crop Pr otection, Inc., Greensboro, NC (Syngenta Number T006608-04). Study co mpleted November 16, 2004.

MRID 468001-23 Friedrich, Sabine. 2001. Acute Toxi city of NOA446510 to the Earthworm Eisenia fetida. Unpublished st udy performed by BioChem agrar, Laboratory for Biological and Chemical Analysis, Ltd., Germany. Laborat ory report number 01 10 48 060. Study sponsored by Syngenta Crop Protection, Inc., Greens boro, NC. Study completed October 29, 2001.