## Page 3 of 45 

# Problem Formulation for the Environmental Fate, Ecological Risk, Endangered Species, and Human Health Drinking Water Exposure Assessments in Support of the Registration Review of Methoxyfenozide

Methoxyfenozide CAS: 161050-58-4 PC Code: 121027

P

repared by: Mary Clock-Rust, Biologist Karen Milians, Ph.D., Chemist U.S. Environmental Protection Agency Office of Pesticide Programs E

nvironmental Fate and Effects Division E

nvironmental Risk Branch IV 1200 Pennsylvania Ave., NW Mail Code 7507P Washington, DC 20460 R eviewed by: Jim Carleton, Ph.D., Senior Scientist Thomas Steeger, Ph.D., Senior Advisor A

pproved by: Marietta Echeverria, Branch Chief



## Date: April 25, 2013

## Page 4 of 45 

# 1. Introduction

The purpose of this problem formulation is to pr ovide an understanding of the environmental fate and ecological effects of the registered uses of methoxyfenozide. Methoxyfenozide is an insect growth regulator, and works by inducing a premature molt in insects. While there are data indicating that the compound does no t affect adult honey bees, there is uncertainty regarding its potential effects on honey bee brood (larvae) . It is currently registered for use on bush berries, cilantro leaves, brassica (cole) l eafy vegetables, leaves of root a nd tuber vegetables , citrus fruit, cotton, cranberry, cucurbit vegetabl es, fruiting vegetables, globe ar tichoke, grape, grass (forage, fodder, and hay), green onions, legume vegetabl es, foliage of legume vegetables, nongrass (forage, fodder, straw, and ha y), peanut, pome fruits, pomegrana te, popcorn, root vegetables, soybean, spearmint, peppermint, ston e fruits, strawberry, tree fruits, tree nut s, and tuberous and corm vegetables (except potato) . Additionally, this compound is registered for non-agricultural

uses on ornamental herbaceous plants, ornamental w oody shrubs and vines, ornamental and/or shade trees, recreational areas/p arks, and institutions (outdoor)

. Methoxyfenozide belongs to the diacyhydrazine cla ss of insecticides that interfere with the binding of the endogenous steroidal molting hor mone 20-hydroxyecdysosone with its nuclear receptor protein complex and, as such, is referr ed to as an ecdysteroid agonist (Dhadilla et al

. 1998; Shimizu et al . 1997). This non-steroidal ecdyson e agonist induces a precocious incomplete molt in invert ebrates, particularly lepidopterans. After in gestion of toxic doses, sensitive larvae stop feeding a nd the molting process initiates prematurely leading to desiccation and ultimately, death. Refer to Table 2 for the chemical structure of methoxyfenozide.

Methoxyfenozide is formulated as wettable powder and flowable c oncentrate that can be applied at bloom by ground sprayer, airblast sprayer, chem igation, or aerial sprayer (wing or rotor, US EPA, 2013). Maximum single applicati on rates of methoxyfenozide can be found for cotton and almonds (0.40 and 0.38 lbs active ingr edient/Acre, respectively).

The crops with the most use in terms of tota l pounds of active ingredie nt are almonds (28%), wine grapes (12%), tomatoes/lettuce/apples (7% each), pistachios (6%), and raisin grapes and soybeans (4%). The crops with the most use in terms of total area treated are almonds (21 %), wine grapes (11 %), lettuce (9%), soybeans and tomatoes (8% each), apples (5%), and raisin grapes and pistachios (4 % each) for the period 2007-2011. On average, the states with the most agricultural usage in terms of pounds a.i. (active ingredient) applied are California (79%), Washington (4%), and Mississippi and Florida (3% each, USEPA 2013) . Further details on the methoxyfenozide usage profile and history, base d partially upon proprieta ry data sources, are provided in the BEAD Chemical Profile (USEPA 2013, Appendix B ).



# 2. Conclusions from Previous Risk Assessments
2.1. Ecological Risk Assessments

## Page 5 of 45 In 2000, two end-use products of methoxyfenoz ide (INTREPID 80WSP and INTREPID 2F) were granted conditional registrati on in order to address uncertai nties identified in the ecological risk assessment of methoxyfenozide. The c onditional registration requirements included (USEPA, 2000):

- Developing protocols, obtaini ng Agency approval, and cond ucting the following studies:

o Bi-valve (mussel) bioaccum ulation study in sediment

o 

## Avian reproduction study (a 2-generati on study or repeating the bobwhite quail ( Colinus virginianus ) reproduction study with addition of measurements of egg shell strength)

o Chronic chironomid sediment study using midge ( Chironomus sp.)

o A sub-acute sediment study using mayfly ( Hexagenia sp.)

o Honey bee brood study

- Three years after use, obtain ing approval for and conducting monitoring of surface water and sediment in a representative sample of high use areas in proximity to surface water.

The registrant has submitted the required data to address the uncertainties associated with methoxyfenozide use, with the exception of the surface water and sediment monitoring study.

The Agency has conducted approximately twenty five risk assessments on methoxyfenozide for new uses and special exemptions in the last decade; these assessments serve as a basis for this problem formulation. The most recent co mprehensive assessment conducted by the Environmental Fate and Effects Division (EFED) for methoxyfenoz ide was issued on November 10, 2011 (USEPA, 2011) for the proposed use of methoxyfenozide on citrus (national use pattern) and root vegetables. Th e major ecological conclusions pr esented in the ecological risk assessments (ERA) were as follows:

 There is potential for adverse effects to Fede rally-listed threatened /endangered (hereafter referred to as “listed”) and non-listed freshwater and estuarine/marine aquatic invertebrates based on acute an d/or chronic exposure.

 There is uncertainty regarding the potentia l effects of methoxyfenozide on larval development of terrestrial invertebrates, including the potential effects of methoxyfenozide on honey bee larval development.

 Direct adverse effects to birds, mammals, fish, and terrestrial and aquatic plants from methoxyfenozide use are not exp ected; however, given the pote ntial for effects on aquatic invertebrate species, indirect effects to all listed animal s and plants are possible.

In the same document, EFED expressed concerns regarding the high pers istence and moderate mobility of methoxyfenozide sugges ting long-term risks above thos e found in the screening-level drinking water assessment. These concerns were particularly due to the expectation that methoxyfenozide could migrate to key aquatic environmental compartments and persist for extended periods of time.

## Page 6 of 45 

# 2.2. Drinking Water Exposure Assessments

The Environmental Fate and Effects Division (E FED) conducted a drinking water assessment of methoxyfenozide in 2011 (USEPA, 2011). The estimated drinking water concentrations (EDWCs) recommended for use in human Health Ef fects Division dietary ri sk assessment were based on the globe artichoke use (highest EDWCs of the agricultural uses). The surface water EDWCs for ground application were 68.8, 42.4, and 30.3 μg a.i./L (parts per billion; ppb) for acute, chronic, and cancer, respectively. The gro undwater EDWC was 4.13 ppb. 

# 2.3. Clean Water Act Programs

Methoxyfenozide is not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act. No section 304(a) ambient water quality criteria or Total Maximum Daily Loads (TMD L) have been developed for methoxyfenozide. 1



## The Agency invites submission of water quality data for this pesticide. To the extent possible, data should conform to the qualit y standards in Appendix A of the OPP Standard Operating Procedure: Inclusion of Impaired Water Bo dy and Other Water Quality Data in OPP’s Registration Review Risk Assessment and Management Process 2 

## , in order to ensure that they can be used quantitatively or qualitativel y in pesticide risk assessments.



# 3. Environmental Fate and Transport

Based on the classification system of Goring et al. (1975), methoxyfenozide is considered very persistent in soil (aerobic soil half-lives rang ing from 336 to 1100 days). The compound is also characterized as mobile to moderately m obile according to th e Food and Agriculture Organization United Nations scale, with organic carbon partition coefficients (K oc 

## ) ranging from 219 to 922 mL/g oc 

## and soil partition coefficients (K d 

## ) ranging from 1.1 to 6.2 mL/g. Because of its resistance to degradation and its mobility, me thoxyfenozide has the poten tial to move off the site of application by leaching, runoff and/ or movement with eroded sediment, and to subsequently accumulate in aquatic systems.

Methoxyfenozide is stable to abiotic routes of degradation, but degrades slowly by aerobic soil metabolism. Methoxyfenozide is non-volatile (based on its Henry’s constant of 1.6 x10 -9



## atm·m 3 

## ·mole -1 

## ), hydrophobic (based on logarithm of the octanol-water partitio n coefficient; log K ow 

## =3.72), and possesses moderate water solubility (3.3 mg/L at 25°C). Although present only in low relative amounts ( i.e. equivalent to less than 10% of applied radioactivity), identified transformation products formed in fate studies were RH-131154, RH-117236, and CO 2 

## , all of which are discussed below. Table 1 provides a summary of chemical and environmental fate properties of methoxyfenozide.

1 

### http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885

2 

### http://www.epa.gov/oppfead1/cb/ppdc/2006/november06/session1-sop.pdf

## Page 7 of 45 Table 1. Chemical Properties and Environmen tal Fate Parameters of Methoxyfenozide.

Parameter Value Description Reference Chemical Classification Diacylhydrazine --

Molecular Formula C 22 

### H 28 

### N 2 

### O 3 

### --
PC Code 121027 --

Chemical Name (IUPAC) n

- tert- butyl-N’-[2-methyl-3- methoxybenzoyl]-3,5- dimethylbenzohydrazide --

Chemical Name (CAS) 3-methoxy-2-methylbenzoic acid 2-(3,5- dimethylbenzoyl)-2-(1,1- dimethylethyl)hydrazide --

CAS Number 161050-58-4 --

Pesticide Classification Insecticide --

USEPA, 2000 Molecular Weight 368 g/mol --

Physical State white powder --
Water Solubility (ppm) 3.3 at 25 o 

### C Moderately soluble

Vapor pressure (25 o 

### C) 2.0 x 10 -8 

### torr Not likely to volatilize from dry surfaces

Henry's Law Constant 1.62 x10 -9 

### atm· m 3 

### ·mole -1 

### (Calculated) Not likely to volatilize from water or wet surfaces Octanol/Water Partition, K ow 

### 5248 (log K ow 

### = 3.72) Hydrophobic-potential to bioaccumulate Persistence Hydrolysis Stable at pH levels of 5, 7, and 9 in a 30 day study period No degradation observed MRID 441444-30

Direct photolysis in water at pH 7 t 1/2 

### = 77 days at pH 6.6 in pond water. Degradates were not identified, but were present at <5% of the AR (up to 7 degradates) Moderately persistent to persistent. Studies suggest that photolysis is not an important degradation pathway MRID 441444-31

Stable in aqueous buffer solution (pH 7)

Degradate RH-131154 was present at ≤ 0.56% in irradiated and dark samples MRID 44617805

Photolysis on soil Stable Degradate RH-131154 was present at <2.0% of the AR in irradiated and dark samples. Persistent Studies indicate that photolysis on soil is not an important degradation pathway MRID 446178-06

Aerobic soil metabolism t 1/2 

### = 1100 days (loamy sand) Persistent Studies exhibited poor extraction of the solid phase and/or loss of 14 

### C over time. MRID 446178-07

t 1/2 

### = 336 and 722 days in loamy sand and sandy clay loam, respectively. MRID 446178-08

t 1/2 

### = 573 days (loam soil) MRID 441444-32

Anaerobic aquatic metabolism t 1/2 

### = 654 days Persistent Poor extraction, and redox and pH information was not submitted MRID 446178-10

## Page 8 of 45 Parameter Value Description Reference
Aerobic aquatic

metabolism t 1/2 

### = 963 days and 387 days in aerobic flooded sandy loam and clay soils, respectively Persistent MRID 446178-09

Field Dissipation

Terrestrial field

dissipation t 1/2 

### = 327 days (sand soil, WA) Persistent MRID 446178-11

t 1/2 

### = 139 days (loamy sand, CA),

151 days (sand soil, GA), and 92 days (loam soil, TX) Dissipates slowly in the environment and leaching was observed (maximum depth of 30 inches) MRID 446178-12

Mobility

Leaching and absorption/desorption K oc 

### and K d 

### in mL/g 267 and 4.2, loam soil 922 and 1.1, loamy sand 678 and 1.2, loamy sand

219 and 6.2, loam soil 365 and 3.8, silt loam Mobile to moderate mobility MRID 441444-33

Fish Bioconcentration Bioconcentration in fish (BCF) 1.1-1.3x for fillet, 16.6-22.1x for viscera, and 9.9-10.5x for whole fish tissues Relatively Low BCF MRID 446178-13
Analytical Methods

Environmental Chemistry Methods (ECM) ECM: soil (835.6100) The method is missing the independent laboratory validation MRID 478099-02

ECM: soil (835.6100) Reviewed by biological and economics analysis division (BEAD) MRID 478099-03

ECM: Water (835.6200) The method is missing the independent laboratory validation MRID 478242-01

AR=Applied Radioactivity Classification of persistency was based on Goring scale, 1975. Mobility was described using Swann et al. scale, 1983.



## As mentioned previously, studies indicate that methoxyfenozide is st able to hydrolysis (at pHs 5, 7, and 9) and to photodegradation on soil. Methoxyf enozide is classified as very persistent in soils using the Goring et al. (1975) system, with aerobic metabolis m half-lives ra nging from 336 days to 1100 days. Aquatic studies demonstrate th at methoxyfenozide is also persistent in water under both aerobic and anaerobic conditions.

## Page 9 of 45 Methoxyfenozide exhibits mobile to moderate mobility (FAO scale, 2000), with K d 

## values ranging from 1.1 to 6.2 mL/g, and K oc 

## 's from 219 to 922 mL/g. Because of the chemical’s persistence, relative mobility, an d potential to accumulate in a quatic systems, the registration granted in 2000 for its use on pome fruit and cotton (USEPA, 2000) was conditional. The conditions of registration required, among other things, a monitoring study to be conducted on surface water and sediment in a representative sample of water bodies in high use areas, to determine whether multiple years of use woul d result in accumulation of methoxyfenozide residues in water and/or sediment . The registrant (Dow Agricu ltural Science; DAS) agreed to sample for methoxyfenozide residues over a two-y ear period in two lotic (flowing) water bodies ( e.g. rivers) and five lentic water bodies ( e.g. ponds) in each of the following states: California, Mississippi, and Michigan. The monitoring repor t is expected to be submitted by DAS in 2014 (USEPA 2011).

In Terrestrial Field Dissipation (TFD) studies performed on sand (WA and GA), loamy sand (CA), and loam (TX) soils, methoxyfenozide applied to fields dissipated with DT 50 

## s (times for 50% dissipation of the parent) ranging from 92 days to 327 days . Methoxyfenozide was detected as deep as 36 inches in the soil in these studi es, at concentrations up to 0.039 ppm, providing evidence of leaching. Metabolites in these studies were not identified.

In a bioconcentration study on juvenile blue gill sunfish ( Lepomis macrochirus ), BCFs (bioconcentration factors) were 1.1x for fillet, 22.1x for viscera, and 10.5x for whole fish tissues; the majority (84- 94%) of residues depurated by 14 days. Based on these data methoxyfenozide does not appear to significantly bioconcentrate in fish; however, uncertainty remains regarding the potential of the compound to bioaccumulate in other taxa, e.g ., aquatic invertebrates. To address this uncertainty, the registrant submitted a bioconcentration study using the freshwater clam ( Corbicula fluminea ). The results of this study indicate that methoxyfenozide does not bioaccumulate. When placed in untreated water, the freshwater clam depurates methoxyfenozide by 95% in roughly 16 days (The study is scientif ically sound and is clas sified as acceptable).



# 3.1. Transformation Products

The predominant degradates of methoxyf enozide are RH-117236 and RH-131154 (See Table 2 for structures and amounts recovered), however these were found only in low relative amounts (1 – 6.7% of applied radioactivity ) in the fate studies.Page 10 of 45Table 2. Methoxyfenozide and Its Environmental DegradatesCode Name/SynonymChemical NameChemical StructureStudy TypeRef.(MRID)Maximum%AR (day)Final %AR(study length)PARENTMethoxyfenozideCAS No.:161050-58-4Formula:C22H28N2O3MW:368 g/molSmile string:Cc1c(OC)cccc1C(=O)NN(C(C)(C)C)C(=O)c2cc(C)cc(C)c2MINOR TRANSFORMATION PRODUCTSRH-117236CAS No.:Formula:C21H26N2O3MW:354.45Smile string:CC1=C(C=CC=C1O[H])C(=O)NN(C(C)(C)C)C(=O)C2=CC(=CC(=C2)C)CAerobic aquaticstudy446178-09In CA, 15.8%(91 d)In TX, 6.7% (60d)In Ca, 3% (365 d)In TX, 1% (365 d)RH-131154CAS No:Formula:C22H26N2O5MW:398.46Smile string:CC1=C(C=CC=C1OC)C(=O)NN(C(C)(C)C)C(=O)C2=CC(=CC(=C2)C(O[H])=O)CAerobic aquaticstudy446178-09 <1% (365 d) <1% (365 d)Anaerobic aquaticstudy446178-10 1.1% (119 d) 0.61% (364 d)Aerobic soilmetabolism446178-08446178-07441444-32-- 1-3% (365 d)CO2CAS No:124-38-9Formula:CO2MW:44.01 g/molSmile string: C(=O)=OAerobic aquaticstudy446178-09 -- <6% (365)Anaerobic aquaticstudy446178-10 -- 3.2% (364)Aerobic soilmetabolism446178-08446178-07441444-32-- 2-5% (365 d)

### Page 11 of 45 

# 4. Receptors

Table 3 and 4 provide summaries of the toxicity endpoint s for aquatic and terr estrial organisms, respectively. These values represent the most sensitive species tested within each taxon to characterize potential acute and chronic e ffects of methoxyfenozide. The tables also provide acute toxicity classifications. Based on the most sensitive toxicity endpoints, methoxyfenozide is classified as moderately toxic to freshwater fish (and to aquaticphase amphibians, for which freshwater fish serve as surrogates), estuarine/marine invertebrates and estuarine/marine fish, and as very highly toxic to freshwater invertebrates on an acute exposure basis ( Table 3 ). In some cases the acute toxicity endpoint is non-definitive and suggests th at the potential acute toxicity of methoxyfenozide to these species may be limit ed by the chemical’s solubility (3.3 mg/L at 25 o 

## C). Toxicity data show effects on surv ival in freshwater fish exposed to methoxyfenozide. The midge ( Chironomus riparius ), a freshwater benthic invertebrate, was the most sensitive species tested on a chronic exposure basis, which resulted in delayed emergence and development of the specie s. No acute toxicity data are available for midge larvae; therefore, an acute-to-chr onic ratio (ACR) was used to calculate an acute freshwater invertebrate endpoint using acute and chronic toxicity data from another aquatic invertebrate, the waterflea ( Daphnia magnia ) 3 

## . This calculation results in an estimated EC 50 

## of 0.05 mg a.i./L for the midge 4



## . Green algae ( Pseudokirchnerie lla subcapitata ) was the most se nsitive aquatic nonvascular plant tested, but the endpoint was non-definitive, i.e ., the effect concentration for 50% mortality of the algae exceeded th e highest concentration tested (EC 50 

## >3.4 mg a.i./L), suggesting that the chemical’s so lubility may limit its impacts on aquatic nonvascular plants. Data on the effects of me thoxyfenozide on vascular plants are not available.

For estuarine/marine invertebrates, chronic toxicity data are av ailable for the mysid ( Americamysis bahia ). In this study reduced growth (length) occurred, with a NOAEC of 0.025 mg a.i./L.

Methoxyfenozide is practically nontoxic to birds (as well as reptiles and terrestrial-phase amphibians, for which birds serve as surroga tes) on both an acute oral and subacute dietary exposure basis; the compound is pr actically nontoxic to mammals on an acute oral exposure basis. Past EFED risk assessm ents used the endpoint of eggshell thinning seen in a reproductive toxi city study with bobwhite qua il (MRID 446177-11) to calculate chronic risk to birds. However, EFED is currently reviewing these and other avian reproductive toxicity data, and will use the re sults of these data to inform the risk assessment for birds. No other effects were obs erved in chronic bird studies. In mammals, chronic exposure resulted in histological chan ges in the liver and in the thyroid gland, and there was uncertainty regarding the exte nt to which methoxyfenozide may affect the

3 

### The most sensitive acute and chronic endpoints available for daphnids are an EC 50 

### of 3.7 mg a.i./L (MRID 441444-11) and a NOAEC of 0.20 mg a.i./L (MRID 446177-14), respectively.
4 

### [(3.7 mg a.i./L)/(0.20 mg a.i./L) = (0.05 mg a.i./L)/(0.0026 mg a.i./L)]

### Page 12 of 45 

## hypothalamic-pituitary-thyroid axis. Because of this uncertainty EFED recommended additional data on amphibians to determine whether thyroid-dependent metamorphosis is affected. The registrant has submitted a study of amphibian metamorphosis following OCSPP Guideline 890.1100 (MRID 489387-01).

Methoxyfenozide is classified as “prac tically nontoxic” to adult honey bees ( Apis mellifera ; Table 4 ), but has been shown to be highly toxic to target insect pests on an acute exposure basis 5 

## . Although methoxyfenozide is inte nded to target lepidopterans, there is uncertainty regarding the extent to which other species of insects and taxa dependent on ecdysone may be affected. B ecause of methoxyfenozide’s mode of action, larval insects, including larval honey bees , may be more sensitive to methoxyfenozide than are adult insects. The registrant has submitted data on red swamp crayfish ( Procambarus clarkia ) and more recently on honeybees to address this uncertainty. Exposure to methoxyfenozide did not affect su rvival, growth (length or weight), total number of molts or number of molts per females in crayfish.

Recently, EFED received three new toxicity studies for methoxyfenozide examining the toxicity to African clawed frog ( Xenopus laevis ) larvae (MRID 489387-01) and honeybee brood, as well as a study of methoxyf enozide residues in bee colonies from almonds treated with methoxyfen ozide (MRIDs 489622-01, 489622-02, 489622-03). These studies are under review in EFED, and w ill be used to inform the risk assessment for methoxyfenozide. 

# 4.1. Effects to Aquatic Organisms

Table 3. Summary of the Most Sensitive Endpoints from Aquatic Toxicity Studies for Methoxyfenozide

Taxonomic

Group Study Type Surrogate Species Toxicity Value (all units in

terms of measured active

ingredient) Acute Toxicity Classification Source (MRID) Study Classification

Freshwater Fish 96-Hour Acute Toxicity Rainbow trout Oncorhynchus mykiss LC 50 >4.2 mg/L 

### (No mortality at the highest treatment level tested) Moderately Toxic 441444-10 Acceptable

Full Life Cycle Toxicity Fathead minnow Pimephales promelas NOAEC = 0.53 mg a.i./L LOAEC = 1.0

(survival) N/A 446177-16 Acceptable

Freshwater Invertebrates Estimate based onAcute-toChronic Ratio 1 Midge Chironomus

riparius EC 50 = 0.05 1 mg a.i./L (mortality) Very highly toxic N/A 1 N/A

5 

### Trisyono, 1997

### Page 13 of 45 Taxonomic

Group Study Type Surrogate Species Toxicity Value (all units in

terms of measured active

ingredient) Acute Toxicity Classification Source (MRID) Study Classification

Chronic Effects on Midge Larvae Midge Chironomus

riparius NOAEC=0.0063 mg a.i./L

LOAEC=0.013 mg a.i./L (Delayed emergence and development) N/A 450328-01 Supplemental

Estuarine/ Marine Fish 96-Hour Acute Toxicity Sheepshead minnow
Cyprinodon variegatus 96-hr LC 50 >2.8 mg a.i./L Moderately Toxic 441444-12 Acceptable

Early Life Stage Toxicity Sheepshead minnow Cyprinodon variegatus N/A N/A 446177-12 Currently under review in EFED

Estuarine/ Marine Invertebrates 96-Hour Shell Depositio

n Eastern oyster

Crassostrea

virginica 96-hr EC 50 = 1.2 mg a.i./L Moderately Toxic 441444-13 Acceptable

Invertebra te Life Cycle Toxicity Mysid
Americamysis bahia ( formerly

Mysidopsis

bahia) NOAEC = 0.025 mg a.i./L LOAEC = 0.051 mg a.i./L (Reduced growth/length) N/A 446177-15 Acceptable

Non-Vascular Aquatic Plants 5-Day Toxicity Test Freshwater alga

Pseudokirchneri ella subcapitata ( formerly Selenastrum capricornutum) EC 50 >3.4 mg a.i./L
NOAEC= 3.4 mg a.i./L

No effects at the highest treatment level tested N/A 446177-18 Acceptable

1 Acute-to-Chronic Ratio (ACR) was used to estimate the acute toxi city for the midge using the ratio of acute to chronic data p oints from studies with Daphnia and the chronic NOAEC from the midge lifecycle test . [(3.7 mg a.i./L)/(0.20 mg a.i./L) = (0.05 mg a.i./L)/(0.0026 mg a.i./L)]



# 4.2. Effects to Terrestrial Organisms

Table 4: Summary of the Most Sensitive Endpo ints from Terrestrial Toxicity Studies for Methoxyfenozide

### Page 14 of 45 Taxonomic

Group Study Type Surrogate Species Toxicity Value (all units in

terms of measured active

ingredient) Acute Toxicity Classification Source (MRID) Study Classification

Birds Acute Oral Toxicity Northern bobwhite quail Colinus virginianus LD 50 >2,250 mg a.i./kg-bw

No effects at highest treatment level tested Practically Non-Toxic 441444-06 Acceptable

Subacute Dietary Toxicity Northern bobwhite quail Colinus virginianus LC 50 >5,870 mg a.i./kg-diet

No effects at highest treatment level tested Practically Non-Toxic 441444-07 Acceptable

Avian Reproduct ive Toxicity Mallard duck Anas platyrhynchos NOAEC=1,000 mg a.i./kg-diet; LOAEC>1,000 mg a.i./kg-diet

No treatment related effects. N/A 446177-10 Supplemental

Mammals Acute oral Toxicity Rat
Rattus norvegicus LD 50 >5,000 mg a.i./kg-bw Acute Toxicity Category 4 441444-15 Acceptable

Chronic Dietary Toxicity Rat
Rattus norvegicus NOAEL = 200 mg a.i./kg LOAEL=8000

mg a.i./kg (Hematological changes, liver

toxicity, histopathology in thyroid) N/A 446177-31 Acceptable

Terrestrial Invertebrates Acute Contact Toxicity Honey bee
Apis mellifera LD 50 >100 μg/bee Practically Non-Toxic 441444-29 Acceptable

Subacute Dietary Toxicity Honey bee
Apis mellifera LC 50 > 100 μg/bee Practically Non-Toxic 446177-17 Supplemental

1 Birds represent surrogates for terrest rial-phase amphibians and reptiles.

### Page 15 of 45 

# 4.3. Ecological Incidents

The ecological incident information system (EIIS) is an OPP database that houses ecological incidents that have been reported to the Agency. When available, EIIS includes date and location of an incident, type and magnitude of effects observed in various species, use(s) of pe sticides known or suspected of contributing to the incident, and results of any chemical re sidue analysis or other anal yses conducted during incident investigation. EIIS incidents are categorized according to th e certainty that the incident resulted from pesticide exposure. The Avian Monitoring System (AIMS) 6 

## is a database administered by the American Bird Conservanc y that contains publicly available data on reported avian incidents invol ving pesticides. Many of th e incidents listed in this database are also in the EIIS.

EIIS returned three incidents for methoxyfenozide. All three were reported bee kills in which methoxyfenozide was mentioned. Two re ported incidents took place in California, and one in New York State ( Appendix C). For all of these incidents, more than one pesticide chemical was named along with me thoxyfenozide. Since methoxyfenozide is not acutely toxic to bees, it is unlikely that it was the cause of the bee kills.

In the Office of Pesticide Programs’ Aggregate Incident Reports, there were no incidents attributed to methoxyfenozide.

AIMS was also searched on February 4, 2013 and revealed no incidents to birds associated with methoxyfenozide. Because of uncertainties regarding the extent to which incidents are reported to EPA, the absence of incident reports cannot be construed as the absence of incidents.

During the risk assessment associated with Registration Review of methoxyfenozide, these databases will be checked again a nd any new incidents will be evaluated to determine if they represent current use patterns of methoxyfenozide.

Table 5. Summary of Methoxyfenozide Incidents

Chemical Name (Product Name) Crop Date Certainty Location Affected Taxa Application Method

Methoxyfenozide

(Intrepid 2F) Pistachios 07/26/11 Unlikely Kings County, CA Honeybees (92 colonies) Ground

Orchard/

Corn Planting 5/11/12 Unlikely Seneca County, NY Honeybees (48 colonies) Corn planted with air planter

Almonds February, 2012 Possible California Honeybees (464 colonies) Unknown

6 

### http://www.abcbirds.org/abcprograms/policy/toxins/aims/aims/login.cfm

### Page 16 of 45 

# 5. Exposure Pathways of Concern

For a pesticide to pose an ecological ris k, it must reach ecological receptors in biologically significant concen trations. An exposure pathway is the means by which a pesticide moves in the environment from a source to an ecological receptor. For an ecological pathway to be complete, it must include a source, a release mechanism, an environmental transport medium, a point of exposure for ecological receptors, and a feasible route of exposure.

The environmental fate properties of met hoxyfenozide indicate the following transport mechanisms for potential exposure to aquatic and terrestrial organisms:

 Direct contact

 Ingestion

 Spray drift

 Runoff

 Leaching

A risk hypothesis describes th e predicted relationship among the stressor, exposure, and assessment endpoint response along with the rationale for their selection. For methoxyfenozide, the following ecological ri sk hypothesis is being employed for this problem formulation:

Based on the application methods, mode of action, fate and transport, and the sensitivity of non-target aqua tic and terrestrial species , methoxyfenozide has the potential to reduce survival, reproduc tion, and/or growth in aquatic organisms (i.e., freshwater fish, estuarine/marine invertebrates and estuarine/marine fish) and terrestrial invertebrates when used in accordance with the current labels. These non-target organisms include listed sp ecies as well as non-listed species.

Potential exposure pathways through drinking water (imbibition) and inhalation were screened using the SIP (Screening Imbibiti on Program) and STIR (Screening Tool for Inhalation Risk) programs, respectively. Result s from the SIP tool showed this exposure pathway to be of low concern, i.e ., there were no exceedances of Agency Levels of Concern (LOC) ( Appendix E ). Screening using the STIR model found inhalation exposures to be of low c oncern in birds and mammals, i.e ., no LOC exceedances are expected via this potential route of exposure ( Appendix E ). SIP and STIR are described in detail at: http://www.epa.gov/oppefed1/ models/terrestrial/index.htm

.

### Page 17 of 45 

# 6. Analysis Plan

In order to address the risk hypothesis, the potential for adverse effects on the environment is estimated. The use, environmental fate, and ecological effects of methoxyfenozide are characteri zed and integrated to asse ss the risks. This is accomplished using a risk quotient (ratio of exposure concentration to effects concentration) approach. Although risk is of ten defined as the likelihood and magnitude of adverse ecological effect s, the risk quotient-based approach does not provide a quantitative estimate of likeli hood and/or magnitude of an a dverse effect. However, as outlined in the Overview Document (USE PA, 2004), the likelihood of effects to individual organisms from particular uses of methoxyfenozide is estimated using the probit dose-response slope and either the leve l of concern (discusse d below) or actual calculated risk quotient value.

This analysis plan will be revisited a nd may be revised depending upon the information submitted by the public in response to the ope ning of the Registration Review docket for methoxyfenozide.



# 6.1. Stressors of Concern

Ecological Risk Assessment

The stressors of concern are as follows:

 Terrestrial Environment: parent methoxyfenozide

 Aquatic Environment: parent methoxyfenozide

There are no major degradates in the environmental fate studies, therefore methoxyfenozide is the sole residue of concern for both the aquatic and terrestrial environments.

An evaluation of environmental pesticide mixtures is beyond the scope of problem formulation because of myriad factors that cannot be quantified based on the available data. Those factors include identification of other po ssible co-contaminants and their concentrations, differences in patterns and durations of exposure among contaminants, and differential effects of other physical/che mical characteristics of the receiving waters ( e.g. organic matter present in sediment and susp ended water). Evaluation of factors that could influence additivity/synergism is be yond the scope of this assessment and the capabilities of the available data to allow fo r an evaluation. The final risk assessment will evaluate, characterize, and potentially make use of data available on combinations of active ingredients with methoxyf enozide, inert products, and/ or environmental mixtures.

Drinking Water

In order to bring the drinking water exposure assessment up to date with current data, models and simulation model guidance, a ne w drinking water assessment (DWA) may be

### Page 18 of 45 

## conducted to support future human health diet ary risk assessments of methoxyfenozide. The DWA will be conducted for the maximum labeled use rate in support of the human health dietary risk assessment. 

# 6.2. Measures of Exposure

EFED will use standard available models (identified in Table 5 ) to evaluate potential exposures to aquatic and terrestr ial organisms as described at http://www.epa.gov/pesticides/science/models_db.htm

. Aquatic exposure estimates will be based on estimated environmental concentrations (EECs) generated using the Pesticide R oot Zone Model (PRZM 3.12.2 dated May 12, 2005) coupled with the Exposure Anal ysis Model System (EXAMS 2.98.04.06 dated April 25, 2005) to simulate a waterbody that is considered representative of vulnerable aquatic environments ( e.g . ponds and streams in headwate r watersheds). Terrestrial exposure will be estimated using a model (T -REX version 1.5) th at assumes direct application to a variety of avian, mammalia n and reptilian food items. Exposure to terrestrial plants will be es timated using a model (TerrPlant ; version 1.2.2) that assumes methoxyfenozide drifts or moves with runoff to adjacent habitats. For more information on the various models that will be used in th e risk assessment see the links as outlined in Table 6

. Two spray drift models, AgDISP and/or AgDR IFT, will be used to assess exposures of aquatic and terrestrial organi sms to methoxyfenozide deposite d in terrestrial and aquatic habitats by spray drift. AgDRIFT (versi on 2.1.1; dated 03/07/2012) is the model most commonly used by EFED to simulate spra y drift into terrestrial and aquatic environments. AgDISP (version 8.26; dated 03/07/2012) is used when a parameter needs to be modeled that is not available in AgDRIFT. Spray drift analysis will be an important part of the analysis in defining the pote ntial area of effects for endangered species.

A downstream dilution model (under developmen t) may be used to identify waters downstream from a use area that may have EEC s high enough to result in a risk concern. Such an analysis would be used to define potential areas of effects for listed species.

Table 6. List of the various models and the related taxa fo r which the models will be used.

Environment Taxa of Concern Model(s) Link

Aquatic Fish/ Invertebrates/Pl
ants PRZM, EXAMS http://www.epa.gov/oppefed1/models/water/

Terrestrial Vertebrate T-REX (dietary item) http://www.epa.gov/oppefed1/models/terrestria l/trex/trex_v1_5_webversion.xlsm

AGDISP (Spray drift) http://www.continuum-dynamics.com/pragdisp.html Plant TerrPlant (Run-off) http://www.epa.gov/oppefed1/models/terrestria l/index.htm#terrplant

### Page 19 of 45 AgDRIFT (Spray drift) http://www.agdrift.com/AgDRIFt2/DownloadA gDrift2_0.htm AGDISP (Spray drift) http://www.continuum-dynamics.com/pragdisp.html



# 6.3. Measures of Effect

The most sensitive toxicity data presented in Section 3 of this problem formulation will be used to calculate risk quotients for the respective taxa. Any additional relevant information submitted by the registrant or f ound in the open literature prior to conduct of the risk assessment will also be considered. The open literature studies are identified using EPA’s ECOTOXicology database (E COTOX) (USEPA, 2007), which employs a literature search engine for locating chemical toxicity data for aquatic life, terrestrial plants, and wildlife. The evalua tion of both sources of data can also provide insight into the direct and indirect effects of pesticides on biotic communities from loss of species that are sensitive to the chemicals, and fr om changes in structural and functional characteristics of affected communities.



# 6.4. Endangered Species Assessments

Consistent with its responsibility under the Endangered Species Act (ESA), the Agency will evaluate risks to listed species from registered uses of methoxyfenozide. These assessments will be conducted in accordance w ith standard EPA procedures and best professional judgment. The process for evalua ting potential risks to listed species is further described in the Overvi ew Document (USEPA, 2004) at http://www.epa.gov/oppfead1/enda nger/litstatus/riskasses.htm

. The assessment of effects associated with regi strations of methoxyfenozide is based on an action area. The action area is considered to be the area directly or indirectly affected by the federal action, as indicated by the exc eedance of Agency LOCs used to evaluate direct or indirect effects. The Agency’s approach to defining the action area under the provisions of the Overview Document (USEPA , 2004) considers the results of the risk assessment process to establish boundaries for that action area with the understanding that exposures below the Agency’s defined LO Cs constitute a no-effect threshold. For the purposes of this assessment, attention will be focused on the footprint of the action ( i.e. , the area where methoxyfenozide applicati on occurs), plus all areas where offsite transport ( i.e. , spray drift, runoff, etc .) may result in potential exposure that exceeds the Agency’s LOCs. Specific measures of ecologi cal effect that define the action area for listed species include any direct and indirect effects and/or potential modification of its critical habitat, incl uding reduction in surv ival, growth, and repr oduction as well as the full suite of sublethal effects av ailable in the effects literature . Therefore, the action area extends to a point where environmental expos ures are below any measured lethal or sublethal effect threshold for any biological entity at the whole organism, organ, tissue, and cellular level of organizati on. In situations where it is not possible to determine the

### Page 20 of 45 

## threshold for an observed effect, the action ar ea is not spatially limited and is assumed to be the entire United States.



# 6.5. Endocrine Disruptor Screening Program (EDSP)

As required by FIFRA and FFDCA, EPA review s numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and chronic toxicit y, including assessments of car cinogenicity, ne urotoxicity, developmental, reproductive, and general or systemic toxi city. These st udies include endpoints which may be sus ceptible to endocrine infl uence, including effects on endocrine target organ histopa thology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, repr oductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute test s and chronic studies that assess growth, developmental and reproductive effects in di fferent taxonomic groups. As part of its reregistration decision, EPA reviewed th ese data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 40 8(p), methoxyfenozide is subject to the endocrine screening part of the Endocrine Disruptor Screenin g Program (EDSP).

EPA has developed the EDSP to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP employs a two-tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical subs tance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to intera ct with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests are necessary based on the avai lable data. Tier 2 testing is designed to identify any adverse endocrine-related effects caused by the substance, and establish a dose-response relationship between the dose and the E, A, or T effect.

Under Federal Food Drug and Cosmetic Act (FFDCA) section 408(p), the Agency must screen all pesticide chemi cals for potential endocrine di sruptor activity. Between October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals, which comprises 58 pesticide active ingredients and 9 inert ingredients. Methoxyfenozide is not among the group of 58 pe sticide active ingred ients on the initial list to be screened under the EDSP. Accord ingly, as part of Registration Review, EPA will issue future EDSP orders/data call-ins, requiring the submission of EDSP screening assays for methoxyfenozide. For further information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website: http://www.epa.gov/endo/

. 

# 7. Preliminary Identification of Data Gaps

### Page 21 of 45 

## EFED presently has sufficient data to c onduct a screening-level assessment of the potential risks to exposure to non-target organi sms. No additional data on the ecological effects of methoxyfenozide are needed at this time. Several ecological effects studies have been recently submitted for methoxyfenozid e to address uncertain ties that had been previously identified regarding the poten tial effects on honeybee larvae and thyroiddependent functions ( e.g ., amphibian metamorphosis), and ar e under review at this time. Tables 7, 8 and 9 summarize the data that have been submitted for the parent compound.

However, data on the environmenta l chemistry methods are needed:

 Environmental Chemistry Methods (ECM) for Water and Associated Independent Laboratory Validation (ILV), OCSPP Guideline 850.6100 to support terrestrial field dissipation study
The environmental chemistry method (ECM; MRID 478242-01) for water was classified as not acceptable, but potentially upgradab le pending submission of an independent laboratory validation (ILV) for the met hod. The ECM study can be upgraded to supplemental or acceptable status if an acceptable ILV is submitted to the Agency.



# 7.1. Environmental Fate

Table 7 identifies environmental fate studies by master record identification (MRID) number that provide data for each guideline re quirement, as well as study classifications and whether or not further data are needed in order to support risk assessment. No environmental fate data for degradates have been submitted; however at this time no studies on methoxyfenozide degr adates are needed for risk assessment, given the low extent to which the degradates form.

Table 7. Submitted Environmental Fate Data for Methoxyfenozide

OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Are data needed to conduct risk assessment? Justification and Assumptions EPA will Make in Absence of Data 835.2120 Hydrolysis 4 41444-30 Acceptable No

835.2370 Aqueous Photolysis 441444-31 Acceptable No

446178-05 Acceptable No

835.2410 Soil Photolysis 446178-06 Acceptable No

835.4100 Aerobic Soil Metabolism 446178-07 Supplemental

No The studies are useful for risk assessment despite the deficiencies. 446178-08 Supplemental

441444-32 Supplemental

835.4200 Anaerobic Soil Metabolism None -- No

835.4300 Aerobic Aquatic Metabolism 446178-09 Supplemental No

### Page 22 of 45 OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Are data needed to conduct risk assessment? Justification and Assumptions EPA will Make in Absence of Data

835.4400 Anaerobic Aquatic Metabolism 446178-10 Supplemental No

835.1230 Adsorption/desorption batch equilibrium 441444-33 Supplemental No

835.1410 Lab Volatility Study None -- No None
835.8100 Field Volatility Study None -- No None

835.7100 Prospective ground water monitoring (PGW) None -- No None

835.6200 Terrestrial Field Dissipation 446178-11 Supplemental No 446178-12 Supplemental

850.1730 Bioconcentration Factor 446178-13 Acceptable No

850.6100 Environmental Chemistry Methods (ECM) and Independent Laboratory Validation (ILV) 478242-01
In water Not acceptable but upgradable Yes Independent laboratory validation method needed to

support submitted ECM.
478099-02

In soil Upgradable No 478099-03

In soil Acceptable



# 7.2. Effects

Table 8 and 9 identify ecological effects studies by MRID number that provide data for each guideline requirement, as well as study cl assifications and whether or not additional data are needed in order to support risk assessment. Ratio nales for the a dditional data requested are presented below Tables 8 and 9

. Table 8. Submitted Aquatic Ecological Effects Data for Methoxyfenozide

OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Are data needed to conduct risk assessment? Justification and Assumptions EPA will Make in Absence of Data

850.1010 Freshwater invertebrate acute toxicity 441444-11 Acceptable No

850.1025 Saltwater invertebrate acute toxicity 441444-13 Acceptable

No

850.1035 441444-14 Acceptable

850.1075 Freshwater fish 441444-09 Acceptable No

### Page 23 of 45 OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Are data needed to conduct risk assessment? Justification and Assumptions EPA will Make in Absence of Data

acute toxicity 4 41444-10 Acceptable

850.1075 Saltwater fish acute toxicity 441444-12 Acceptable No

850.1300 Freshwater invertebrate

life cycle 446177-14 Acceptable No

850.1350 Saltwater invertebrates

life cycle 446177-15 Acceptable No

850.1400 Freshwater fish early-life stage 446177-13 Acceptable No

850.1400 Saltwater fish early-life stage 446177-12 -- No Under review in EFED

850.1500 Fish life cycle 446177-16 Acceptable No

850.4400 Aquatic plant growth: Tier II vascular plants 446177-18 Acceptable No

890.1100 3 

### Amphibian Metamorphosis ( Xenopus ) under flow through conditions 489387-01 -- -- Under review in EFED

1 

### The study was classified as acceptable; however, the NOAEC was non-definitive
2 

### The study was classified as supplemental; however, data provided in the study report can be used for risk estimation.
3 

### This study was not submitted in response to the Endo crine Disruptor Screening Pr ogram (EDSP) test order
proram. 

## Table 9. Submitted Terrestrial Ecologica l Effects Data for Methoxyfenozide

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

assessment? Justification and Assumptions EPA will Make in Absence of Data

850.2100 Avian oral toxi city 441444- 06 Acceptable No

850.2200 Avian dietary toxicity 441444-07 Acceptable No 441444-08 Acceptable
850.2300 Avian reproduction 446177-10 Supplemental No

### Page 24 of 45 OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Are data needed for risk

assessment? Justification and Assumptions EPA will Make in Absence of Data
456528-01 Acceptable

446177-11 --- Under review in EFED

850.3020 Honey bee acute contact toxicity 441444-29 Acceptable No

NonGuideline

Study Honeybee subacute dietary toxicity 446177-17 Acceptable No

NonGuideline

Study Honeybee brood development 483505-01 Supplemental No

NonGuideline

Study Honeybee brood development 450655-01 Supplemental No

850.3040 Honeybee brood development 489622-01 -- -- Under review in EFED

850.3040 Almond orchard study of residues in

honeybees and honeybee products 489622-02 -- -- Under review in EFED



# 8. References

Literature Cited

Burns, Lawrence (2004). Exposure Analysis Modeling System (EXAMS): User Manual and System Documentation. Ecosystem Research Division, National Exposure Research Laboratory. U. S. Environmental Protection Agency, Athens, GA.

California Department of Pesticide Regulation (C DPR) (2003). Methoxyfenozide. Public Report 2003-3. Tracking ID Numbers 195668 and 196546.

California Department of Pesticide Regulation (CDPR) Surface Water Database (CDPR 2006).

Carsel, R.F., J.C. Imhoff, P.R. Humel, J.M. Cheplick, and A.S. Donigian, Jr. (2005). PRZM-3, A Model for Predicting Pesticide and Nitroge n Fate in the Crop Root and Unsaturated Zones: User’s Manual for Release 3.12.2. National Exposure Research Laboratory, Office of Research and Development, U. S. Environmental Protection Agency, Athens, GA. Dhadialla, T. S., G. R. Carlson, and D. P. Le . (1998). New insecticides with ecdysteroidal and juvenile hormone activity. Annual Reviews in Entomology 43: 545 - 569.

Markle, G.M., J. J. Baron, and B.A. Schneider. (1998). Food and Feed Crops of the United States. Second Ed. , MeisterPro Reference Guides. Willoughby, Ohio. Monograph # 86,

### Page 25 of 45 199, 244, 507, 524, 587.

Shimizu, B., Y. Nakagawa, K. Hattori, K. Nish imura, N. Kurihara, and T. Ueno (1997). Molting hormonal and larvicidal activities of alip hatic acyl analogs of dibenzoylhydrazine insecticides. Steroids 62 (10): 638 - 642.

Trisyono, A., and G. M. Chippendale (1997). Effect of the non-steroidal ecdysone agonists, methoxyfenozide and tebufenozide, on the European corn borer (Lepidoptera; Pyralidae). J. Econ. Entomol ., 90: 1486-1492. (ECOTOX No.: 64128).

Goring, C.A. I.; Laskowki; D.A., Hamaker, J.H.; and Meikle, R.W. 1975. Principles od pesticide degradation in soil. pp. 135-172 in (Haque, R. and Freed, V.H. eds.) Environmental dynamics of pesticides. Plenum Press, NY.

USDA Crop Profiles. Available online at: http://www.ipmcenters.org/cropprofiles/CP_form.cfm

USEPA (2000). Memo: Conditional Registration of the New Active Ingredient , benzoic acid, 3- methoxy-2-methy-, 2-(3,5-dimethylbenzoyl)-2-(1,1-dimethyl)hydrazide (Methoxyfenozide) a New Insecticide, for Control of Lepedopterian Pests in or on Cotton and Pome Fruits. From James Jones (RD) to Susan Hazen (OPP), dated June 9, 2000.

USEPA (2000 a ). Memo: Proposed Tiered Mitigation for Methoxyfenozide. From Dirk Young and Thomas Steeher (EFED) to Joseph Tava no and Arnold Layne (RD), dated April 10, 2000.

USEPA (2000 b ). Memo: Endangered Species Assessment for the Proposed Section 3 Registration of Methoxyfenozide on Apples. From Arthur-Jean Williams (FEAD) to Arnold Layne (RD), dated June 21, 2000.

USEPA (2001 a ). EFED Risk Assessment for Sectio n 3 Registration of Methoxyfenozide (INTREPID TM 

### ). From Dirk Young (EFED), Dana Spatz (EFED), and Thomas Steeger (EFED) to Joseph Tavano (RD) and Arnol d Layne (RD). DP Barcodes - D249466, D249447, D231307, and D231310.

USEPA (2001 b ). Addendum to EFED’s Review of Propo sed Protocols for Data Required Under Conditional Registration for Methoxyfe nozide. U.S. Environmental Protection Agency, Office of Pesticide Programs, Environmental Fate and Effects Division. July 25, 2001.

USEPA (2002). Guidance for Selecting Input Para meters in Modeling the Environmental Fate and Transport of Pesticides, Version II. Office of Pesticide Programs. Washington, D.C. February 28, 2002. http://www.epa.gov/oppefed1/models/w ater/input_guidance2_28_02.htm

USEPA (2004). Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs. U.S. Environmental Protection Agency, Endangered and Threatened Species Effects Determinations, Office of Preventi on, Pesticides and Toxic Substances Office of Pesticide Programs, Washington, D.C. 100 pgs. January 23.

### Page 26 of 45 USEPA (2006). Crop Grouping – Part II: Analysis of the USDA IR-4 Petition to Amend the Crop Group Regulation 40 CFR ' 180.41 (c) (13) and Commodity Definitions [40 CFR ' 180.1 (h)] Related to Crop Group 13 Berry . MRID 467975-01. Bernard A. Schneider, Ph.D., March 28, 2006.

USEPA. (2009). Ecological Risk Assessment fo r the Methoxyfenozide Section 3 New Uses on Dried Shelled Pea and Bean (Crop Subg roup 6C, Except Soybean), Pomegranate, Popcorn, and Citrus (Crop Group 10). U.S. Environmental Protection Agency, Office of 

## Pesticide Programs, Environmental Fa te and Effects Division. June 30, 2009.

USEPA. (2010). Review of draft protocol surface water and sediment monitoring for metoxyfenoxide (MRID: 478099-04). From Chuck Peck (EFED) and Mark Corbin (EFED) to Mark Suarez (RD) and Richard Gebken (RD). DP barcode 368685. July 19, 2010.

USEPA. (2011). Review of Addendum to Site Selecti on Report with Recommended Alternate Sampling Sites for Lentic Water Bodies in California (MRID 47809904) (MRID: 478099-04). From Chuc k Peck (EFED) and Marietta Echeverria (EFED) to Clayton Myers (RD) and Richard Gebken (PRD). DP barcode 394308. October 12, 2011.

USEPA. 2011. Drinking Water Assessment for the IR-4 New Use Petitions for the Use of Methoxyfenozide on Root Vegetables for Crop Subgroup 1B (Except Sugar Beets) and Citrus Crop Group 10. Envir onmental Fate and Effects Division (K. Milians and C. Sutton) to Registra tion Division (R. Gebken and C. Myers). August, 2011.

USEPA. 2013. BEAD Chemical Profile for Regi stration Review: Methoxyfenozide (121027) . Memorandum From Don Atwood
, Jihad Alsadek and Stephen Smearman to Bonnie Alder. Biological and Economic Analysis Division to Pesticide Reevaluation Division. January 10, 2013.

Food and Agriculture Organization of the Unite d Nations. FAO Pesticide Disposal Series 8. Assessing Soil Contamination: A Reference Manual. Appendix 2. Parameters of pesticides that influence proce sses in the soil. Editorial Group, FAO Information Division: Rome, 2000. http://www.fao.org/docrep/003/X2570E/X2570E00.htm

. Whalen, J., and M. Spellman (1993). Control of lepidopterous larvae on spring cabbage, 1992. Entomological Society of America Journal , 18:115-116.

### Page 27 of 45 

## Appendices

Appendix A. Submitted Environmen tal Fate and Effects Studies

SUBMITTED FATE STUDIES (as of 11/8/12)

63-17 Storage stability

MRID Citation Reference
44144405 Guo, Y. (1996) Product Chemistry for RH-2485 80WP Agricultural Insecticide: Lab Project Number: 96-176: AGDSR-96-176: 33P-95-06. Unpublished study prepared by Rohm and Haas Co. 157 p.
44867601 Young, D. (1999) Product Chemistry for RH-2485 2F Agricultural Insecticide: Lab Project Number: 99-188: 14 100 5043: APR-98-210-01. Unpublished study prepared by Bayer AG. 211 p.
44873402 Molan, K. (1999) Product Chemistry Series 830 Group B Guideline Numbers 830.6317 and 830.6320: Storage Stability and Corrosio n Characteristics of RH-112485 Technical (Supplement to MRID 44144403): Lab Project Number: APR-99-141: 1409.37: 29P-98-32. Unpublished study prepared by Rohm and Haas Company. 14 p. {OPPTS 830.6317, 830.6320}
44873403 Leger, A. (1998) Supplemental Report for RH-2485 80WP Agricultural Insecticide ProductChemistry: Supplement to MRID No. 44144405: Lab Project Number: 96-176: 98-079: 33P95-07. Unpublished study prepared by Rohm and Haas Company. 42 p.

161-1 Hydrolysis

MRID Citation Reference
44144430 Lin, M. (1994) RH-2485 Hydrolysis Study: Lab Project Number: 34-94-49: 34P-94-19. Unpublished study prepared by Rohm and Haas Co. 104 p.

161-2 Photodegradation-water

MRID Citation Reference
44144431 Reynolds, J. (1994) Pond Water Photolysis of (carbon-14)RH-2485: Lab Project Number: 94007: RPT00180: 34P-94-16. Unpublished study prepared by XenoBiotic Labs., Inc. 94 p.
44617805 Smalley, J.; Reynolds, J. (1997) Aqueous Photolysis of (carbon 14)-RH-2485: Lab Project Number: XBL96081: RPT00289: 34P-96-19. Unpublished study prepared by Xenobiotic Laboratories. 80 p.

161-3 Photodegradation-soil

MRID Citation Reference

44617806 Reynolds, J. (1996) Soil Photolysis of (carbon 14)-RH-2485: Lab Project Number: 95044: RPT00262: 34-96-35. Unpublished study prepared by Xenobiotic Laboratories. 108 p.

### Page 28 of 45 162-1 Aerobic soil metabolism

MRID Citation Reference

44144432 Reynolds, J. (1996) Aerobic Soil Metabolism of (carbon-14)-RH-2485: Lab Project Number: XBL94005: RPT00195: 34P-94-14. Unpublished st udy prepared by XenoBiotic Labs., Inc. 198
p. 44617807 Smalley, J. (1997) Aerobic Soil Metabolism of (carbon 14)-RH-2485 in a Loamy Sand from Ohio: Lab Project Number: XBL95007: RPT00263: 34P-95-43. Unpublished study prepared by Xenobiotic Laboratories. 110 p.
44617808 Smalley, J. (1997) Aerobic Soil Metabolism of (carbon 14)-RH-112,485 in Georgia and Texas Soils: Lab Project Number: XBL95047: RPT00303: 34P-95-91. Unpublished study prepared by Xenobiotic Laboratories. 127 p.

162-3 Anaerobic aquatic metabolism

MRID Citation Reference

44617810 Kim-Kang, H.; Reynolds, J. (1996) Anaerobic Aquatic Metabolism of (carbon 14)-RH-2485: Lab Project Number: XBL94006: RPT00230: 34P-94-15. Unpublished study prepared by Xenobiotic Laboratories. 111 p.

162-4 Aerobic aquatic metabolism

MRID Citation Reference

44617809 Smalley, J. (1998) Aerobic Aquatic Metabolism of (carbon 14)-RH-2485: Lab Project Number: XBL96082: RPT00337: 34P-96-20. Unpublished study prepared by Xenobiotic Laboratories. 140 p.

163-1 Leaching/adsorption/desorption

MRID Citation Reference

44144433 Carpenter, D. (1996) RH-2485: Soil Adsorption and Desorption: Lab Project Number: 34-95- 134: XBL 94005: 94-224. Unpublished study prepared by Rohm and Haas Co. 209 p.

164-1 Terrestrial field dissipation

MRID Citation Reference

44617811 Dong, L. (1998) Terrestrial Field Dissipation of RH-2485 on Bare Soil in Washington: Lab Project Number: 1409.26: 34P-96-28: 34P-96-28D. Unpublished study prepared by Qualls Agricultural Laboratory, Inc. and Grayson Research, LLC. 424 p.
44617812 Dong, L. (1998) Terrestrial Field Dissipation of RH-2485 on Bare Soil in California, Georgia, Texas, and Washington (Final Report for California, Georgia, and Texas Sites): Lab Project Number: 34P-96-28: 34P-96-28A: 34P-96-28B. Unpublished study prepared by Agvise

### Page 29 of 45 Laboratories, Inc. and Grayson Research, LLC. 911 p.
45702701 Deakyne, R. (2002) RH-2485 Long--Term Accumulation Study in Washington: Lab Project Number: 34-01-84: 34P-96-28: 34P-96-28D. Unpublished study prepared by Qualls Agricultural Laboratory, Inc., Grayson Research, LLC and Centre Analyti cal Laboratories, Inc. 508 p.



## SUBMITTED EFFECT STUDIES (as of 2/4/13)

71-1 Avian Single Dose Oral Toxicity

MRID Citation Reference
44144406 Campbell, S.; Beavers, J. (1995) RH-112,485 Technical: An Acute Oral Toxicity Study with the Northern Bobwhite: Lab Project Number: 129-155: 95RC-0008: 129/011095/QLD.NC/CHP83. Unpublished study prepared by Wildlife International Ltd. 47 p.

71-2 Avian Dietary Toxicity

MRID Citation Reference
44144407 Campbell, S.; Beavers, J. (1995) RH-112,485 Technical: A Dietary LC50 Study with the Northern Bobwhite: Lab Project Number: 129-156: 95RC-0007: 129/91095/QLCSTD.WC/CHP83. Unpublished study prepared by Wildlife International Ltd. 64 p.
44144408 Campbell, S.; Beavers, J. (1995) RH-112,485 Technical: A Dietary LC50 Study with the Mallard: Lab Project Number: 129-157: 95RC-0009: 129/011095/MLCSDT.WC/CHP83. Unpublished study prepared by Wildlife International Ltd. 64 p.

71-4 Avian Reproduction

MRID Citation Reference
44617710 Frey, L.; Beavers, J.; Martin, K. et al. (1998) RH-112,485 Technical: A Reproduction Study with the Mallard (Anas platyrhynchos): Lab Project Number: 97RC-0101: 129-159: RH112,485M-96-1. Unpublished study prepared by Wildlife International Ltd. 316 p.
44617711 Bennett, R. (1998) Avian Reproduction Study of RH-112,485 Technical with Northern Bobwhite: Lab Project Number: 96RC-0041: RH2485BW-96-2: 96P-043. Unpublished study prepared by Ecological Planning and Toxicology, Inc. 256 p.
45652801 Mitchell, L.; Martin, K.; Beavers, J.; et al. (2001) RH-112,485 Technical: A Reproduction Study with the Northern Bobwhite Quail: Fi nal Report: Lab Project Number: 01RC-0091: 129- 177. Unpublished study prepared by Wildlife International, Ltd. 237 p.

72-1 Acute Toxicity to Freshwater Fish

MRID Citation Reference
44144409 Graves, W.; Swigert, J. (1995) RH-112,485 Technical: A 96-Hour Flow-Through Acute

### Page 30 of 45 Toxicity Test with the Bluegill (Lepomis m acrochirus): Final Repor t: Lab Project Number: 129A-125: 95RC-0026: 129/013195/BLU-96H2/CHP83. Unpublished study prepared by Wildlife International Ltd. 90 p.
44144410 Graves, W.; Swigert, J. (1995) RH-112,485 Technical: A 96-Hour Flow-Through Acute Toxicity Test with the Rainbow Trout (Onc orhynchus mykiss): Final Report: Lab Project Number: 129A-124: 95RC-0025: 129/013195/RBT-96H2/CHP84. Unpublished study prepared by Wildlife International Ltd. 90 p.

72-2 Acute Toxicity to Freshwater Invertebrates

MRID Citation Reference
44144411 Holmes, C.; Swigert, J. (1993) RH-112,485 Technical: A 48-Hour Flow-Through Acute Toxicity Test with the Cladoceran (Daphnia magna): Final Report: Lab Project Number: 129A112B: 92RC-0028: 129/032692/DAP-48H2/CHP38. Unpublished study prepared by Wildlife International Ltd. 93 p.

72-3 Acute Toxicity to Estuarine/Marine Organisms

MRID Citation Reference
44144412 Graves, W.; Swigert, J. (1995) RH-112,485 Technical: A 96-Hour Flow-Through Acute Toxicity Test with the Sheepshead Minnow (Cyprinodon variegatus): Final Report: Lab Project Number: 129A-127: 95RC-0031: 129/013195/SHE-96H2/CHP83. Unpublished study prepared by Wildlife International Ltd. 91 p.
44144413 Graves, W.; Swiger t, J. (1995) RH-112,485 Technical: A 96-Hour Shell Deposition Test with the Eastern Oyster (Crassostrea virginica): Final Report: Lab Project Number: 129A-128: 95RC-0032: 129/012395/OYS-DEP/CHP83. Unpublished study prepared by Wildlife International Ltd. 99 p.
44144414 Graves, W.; Swigert, J. (1995) RH-112,485 Technical: A 96-Hour Flow-Through Acute Toxicity Test with the Saltwater Mysid (Mysid opsis bahia): Final Report: Lab Project Number: 129A-129: 95RC-0033: 129/012095/MYS-96H2/CHP83. Unpublished study prepared by Wildlife International Ltd. 90 p.

72-4 Fish Early Life Stage/ Aquatic Invertebrate Life Cycle Study

MRID Citation Reference
44617712 Graves, W.; Mank, M.; Swigert, J. (1996) RH-112,485 Technical: An Early Life-Stage Toxicity Test with the Sheepshead Minnow (Cyprinodon variegatus): Final Report: Lab Project Number: 129A-134A: 96RC-0044: 96P-044. Unpublished study prepared by Wildlife International Ltd. 121 p.
44617713 Graves, W.; Mank, M.; Swigert, J. (1995) RH-112,485 Technical: An Early Life-Stage Toxicity Test with the Fathead Minnow (Pime phales promelas): Final Report: Lab Project Number: 129A-126: 95RC-0027: 129/013195/FAT-ELS/CHP84. Unpublished study prepared by Wildlife International Ltd. 148 p.
44617714 Zelinka, E.; Holmes, C.; Martin, K. et al. (1993) RH-112,485 Technical: A Flow-Through Life-Cycle Toxicity Test With the Cladoceran (Daphnia magna): Amended Final Report: Lab Project Number: 129A-113B: 92RC-0029: 129/032692/DAP-LC2/CHP38. Unpublished study prepared by Wildlife International Ltd. 108 p.

### Page 31 of 45 44617715 Graves, W.; Mank, M.; Swigert, J. (1996) RH-112,485 Technical: A Flow-Through Life-Cycle Toxicity Test With the Saltwater Mysid (Mysidopsis bahia): Final Report: Lab Project Number: 129A-133A: 95RC-0217: 95P-217. Unpublished study prepared by Wildlife International Ltd. 130 p.
45702702 Sousa, J. (2002) Methoxyfenozide (RH-2485) Technical: Effects on Early Life-Stage Molting and Growth in Red Swamp Crayfish (Procambarus clarkii): Lab Project Number: 12550.6188: 011267: 86.6234. Unpublished study prepared by Springborn Smithers Laboratories. 89 p. {OPPTS 850.1400, 850.1300}

72-5 Life cycle fish

MRID Citation Reference
44617716 Rhodes, J.; Hurshman, B. (1998) Full Life-Cycle Toxicity of RH-112,485 Technical to the Fathead Minnow (Pimephales promelas) Un der Flow-Through Conditions: Lab Project Number: 43701: 96RC-0184: 96P-184. Unpublished study prepared by ABC Laboratories. 1246 p.

72-6 Aquatic org. accumulation- Mollusc

MRID Citation Reference
45702704 Dionne, E. (2002) RH-112,485 Technical--Flow-Through Bioconcentration Study with Asian Clams (Corbicula fluminea): Lab Project Number: 86.6242: 01RC-0090: 01P-090. Unpublished study prepared by Springborn Smithers Laboratories. 71 p. {OPPTS 850.710}

72-7 Aquatic Field Study

45032802 Giddings, J. (1999) Response and Recove ry of Aquatic Communities Exposed to RH-2485 240 SC in Indoor Microcosms Representing Shallow Freshwater Lentic Ecosystems: Final Report: Lab Project Number: 99RC-0052: HBF/MT 09: 86.6233. Unpublished study prepared by Springborn Labs., Inc. 295 p.

123-2 Aquatic plant growth

MRID Citation Reference
44617718 Thompson, S.; Swigert, J. (1995) RH-112, 485 Technical: A 5-Day Toxicity Test with the Freshwater Alga ( Pseudokirchneriella subcapitata formerly Selenastrum capricornutum ): Final Report: Lab Project Number: 129A-130: 95RC-0028: 129/012495/SEL5D2WC/CHP84. Unpublished study prepared by Wildlife International Ltd. 119 p.

141-1 Honey bee acute contact

MRID Citation Reference
44144429 Kirkland, R. (1995) Acute Contact Toxicity of RH-112,485 Technical to Honey Bees: Final Report: Lab Project Number: BIO 166-95: 95RC-0130: 166-95. Unpublished study prepared by Bio Research. 52 p.

### Page 32 of 45 141-4 Honey Bee Subacute Dietary Toxicity

MRID Citation Reference
44617717 Kirkland, R. (1995) Oral Toxicity of RH-112,485 Technical to Honey Bees: Lab Project Number: 167-95: 95RC-0137: 95P-137. Unpublished study prepared by Bio Research. 59 p.

141-? Honeybee Reproductive Effects 48350501 Thompson, H. (2010) Methoxyfenozide: Effects on Honeybee Brood (Apis mellifera) Development. Unpublished study prepared by The Food and Environment Research Agency. 11 p.
45065501 Schmitzer, S. (1997) Study on the Effects of RH 2485 SC 240 (Insect Growth-Regulating Insecticide) on Honey Bee Brood (Apis mell ifera L.) (Hymenoptera , Apidae): Lab Project Number: 2520031: 98RC-1007. Unpublished study prepared by IBACON GmbH. 34 p.

850 Aquatic Insect Toxicity – Acute and Chronic Toxicity 45032801 Kolk, J. (2000) RH-2485 Technical: Chronic Effects on Midge Larvae (Chironomus riparius)in Water/Sediment System: Final Report: Lab Project Number: 99P-001: 1007.051.173: 99RC0001. Unpublished study prepared by Springborn Labs. (Europe) AG. 119 p.
45702703 Stubblefield, W. (2002) RJ-2485 240 SC T oxicity Test Results with the Mayfly, Baetis tricaudatus: Lab Project Number: BJK061802: 99RC-0269. Unpublished study prepared by ENSR. 7 p.
44976901 Heimbach, F. (1999) Influence of RH-2485 (tech.) on Development and Emergence of Larvae of Culex quinquefasciatus in a Water-Sediment System: Lab Project Number: HBF/CH 37: CH 14/99. Unpublished study prepared by Bayer AG. 31 p.

Non Guideline Selections 44617719 Palmer, S.; Beavers, J. (1995) RH-112,485 Technical: An Acute Toxicity Study with the Earthworm in an Artificial So il Substrate: Final Report: Lab Project Number: 129-158: 95RC0030: 95P-030. Unpublished study prepared by Wildlife International Ltd. 72 p.
48938701 Amphibian Metamorphosis ( Xenopus ) under flow through conditions
48962201 Honeybee brood development
48962202 Almond orchard study of residues in honeybees and honeybee products
48962203 Proposed risk analysis for honeybees, based on the two aforementioned honeybee studies.

### Page 33 of 45 

## APPENDIX B- Biological and Economic Analysis Division (BEAD) Report

methoxyfenozide BCP



## Label Data Report for Methoxyfenozide as of 01/30/13

Use Site Aerial and/or Ground Application Identified by Equipment/Lab

el Restriction Application Method Type Desc Maximum Single Application Rate (lb/acre) Max # Apps /

CC A. I. Max App Rate/CC (lb/acre) Max # Apps / Year A. I. Max App Rate/Ye

ar (lb/acre) Minimum Retreatment

Interval

(days) Registration Numbers

Acerola (West Indies cherry) Aerial Spray 0.2386 NS NS NS 0.9543 6 62719-442 (1)

Acerola (West Indies cherry) Ground Spray 0.2386 NS NS NS 0.9543 6 62719-442 (1)

Alfalfa Aerial Spray 0.2386 NS 0.9543 NS NS 7 CA060013 (1)

Alfalfa Ground Spray 0.2386 NS 0.9543 NS NS 7 CA060013 (1)

Almond Aerial Spray 0.3579 NS NS NS 0.9543 10 62719-442 (1)

Almond Ground Spray 0.3579 NS NS NS 0.9543 10 62719-442 (1)

Artichoke Aerial Spray 0.2386 4 NS NS 0.9543 NS 62719-442 (1)

Artichoke Ground Spray 0.2386 4 NS NS 0.9543 NS 62719-442 (1)

Avocado Aerial Spray 0.2386 NS NS NS 0.9543 6 62719-442 (1)

Avocado Ground Spray 0.2386 NS NS NS 0.9543 6 62719-442 (1)

BeandDried Type Aerial Low volume
spray (concentrate) 0.2386 NS NS 4/YR 0.9543 7 WY120005 (1)

Bushberries Aerial Spray 0.2386 NS NS 3/YR 0.7157 7 62719-442 (1)

Bushberries Ground Spray 0.2386 NS NS 3/YR 0.7157 7 62719-442 (1)

Canistel Aerial Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)

Canistel Ground Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)

Carambola

(Jalea) Aerial Spray 0.2386 NS NS NS 0.9543 6 62719-442 (1)

Carambola

(Jalea) Ground Spray 0.2386 NS NS NS 0.9543 6 62719-442 (1)

Cherry Aerial Spray 0.2386 NS NS NS 0.8648 10 62719-442 (1)

CHERRY Ground Spray 0.2386 NS NS NS 0.8648 10 62719-442 (1)

### Page 34 of 45 Use Site Aerial and/or Ground Application Identified by Equipment/Lab

el Restriction Application Method Type Desc Maximum Single Application Rate (lb/acre) Max # Apps /

CC A. I. Max App Rate/CC (lb/acre) Max # Apps / Year A. I. Max App Rate/Ye

ar (lb/acre) Minimum Retreatment

Interval

(days) Registration Numbers

Christmas
tree plantations Aerial Spray 0.2386 NS NS NS 0.4771 10 62719-442 (1)

Christmas
tree plantations Ground Chemigation 0.2386 NS NS NS 0.4771 10 62719-442 (1)

Christmas
tree plantations Aerial Spray 0.2386 NS NS NS 0.4771 10 62719-442 (1)

Citrus Ground Spray 0.1789 NS NS 4/YR 0.7157 7 CA070015 (1)

Citrus Aerial Low volume
spray (concentrate) 0.2386 NS NS NS 0.9543 14 62719-442 (1)

Citrus Ground Spray 0.1789 NS NS 4/YR 0.7157 7 CA070015 (1)

Citrus Aerial Spray 0.2386 NS 0.9543 NS NS 14 FL100001 (1)

Citrus Ground Spray 0.2386 NS NS NS 0.9543 14 62719-442 (1)

Cole Crops Aerial Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)

Cole Crops Ground Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)

Coriander Aerial Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)

Coriander Ground Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)

Corn, Field Aerial Broadcast 0.2386 NS NS NS 0.9543 5 62719-442 (1)

Corn, Field Aerial Spray 0.2386 NS NS NS 0.9543 5 62719-442 (1)

Corn, Field Ground Broadcast 0.2386 NS NS NS 0.9543 5 62719-442 (1)

Corn, Field Ground Directed spray 0.2386 NS NS NS 0.9543 5 62719-442 (1)

Corn, Field Ground Spray 0.2386 NS NS NS 0.9543 5 62719-442 (1)

Corn, Pop Aerial Broadcast 0.1193 NS NS NS 0.9543 5 62719-442 (1)

Corn, Pop Aerial Directed spray 0.1193 NS NS NS 0.9543 5 62719-442 (1)

Corn, Pop Aerial Spray 0.1193 NS NS NS 0.9543 5 62719-442 (1)

Corn, Pop Ground Broadcast 0.1193 NS NS NS 0.9543 5 62719-442 (1)

Corn, Pop Ground Directed spray 0.1193 NS NS NS 0.9543 5 62719-442 (1)

Corn, Pop Ground Spray 0.1193 NS NS NS 0.9543 5 62719-442 (1)

Corn, Sweet Aerial Broadcast 0.2386 NS NS NS 0.9543 5 62719-442 (1)

### Page 35 of 45 Use Site Aerial and/or Ground Application Identified by Equipment/Lab

el Restriction Application Method Type Desc Maximum Single Application Rate (lb/acre) Max # Apps /

CC A. I. Max App Rate/CC (lb/acre) Max # Apps / Year A. I. Max App Rate/Ye

ar (lb/acre) Minimum Retreatment

Interval

(days) Registration Numbers

Corn, Sweet Aerial Spray 0.2386 NS NS NS 0.9543 5 62719-442 (1)

Corn, Sweet Ground Broadcast 0.2386 NS NS NS 0.9543 5 62719-442 (1)

Corn, Sweet Ground Directed spray 0.2386 NS NS NS 0.9543 5 62719-442 (1)

Corn, Sweet Ground Spray 0.2386 NS NS NS 0.9543 5 62719-442 (1)

Corn (unspecifie d) Aerial Broadcast 0.2386 NS NS NS 0.9543 5 62719-442 (1)

Corn (unspecifie d) Aerial Spray 0.2386 NS NS NS 0.9543 5 62719-442 (1)

Corn (unspecifie d) Ground Broadcast 0.2386 NS NS NS 0.9543 5 62719-442 (1)

Corn (unspecifie d) Ground Directed spray 0.2386 NS NS NS 0.9543 5 62719-442 (1)

Corn (unspecifie d) Ground Spray 0.2386 NS NS NS 0.9543 5 62719-442 (1)

Cotton (unspecifie d) Aerial Spray 0.1491 NS NS NS 0.9543 10 62719-442 (1)

Cotton (unspecifie d) Aerial Spray 0.4 NS 1 NS NS NS 62719-438 (1)

Cotton (unspecifie d) Ground Spray 0.1491 NS NS NS 0.9543 10 62719-442 (1)

Cotton (unspecifie d) Ground Spray 0.4 NS 1 NS NS NS 62719-438 (1)

Cranberry Aerial Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)

Cranberry Ground Chemigation 0.2386 NS NS NS 0.9543 10 62719-442 (1)

Cranberry Ground Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)

Cucurbit Vegetables Aerial Spray 0.1491 4 NS NS 0.9543 7 62719-442 (1)

Cucurbit Vegetables Ground Spray 0.1491 4 NS NS 0.9543 7 62719-442 (1)

Feijoa (pineapple

guava) Aerial Spray 0.2386 NS NS NS 0.9543 6 62719-442 (1)

Feijoa (pineapple

guava) Ground Spray 0.2386 NS NS NS 0.9543 6 62719-442 (1)

Filbert (hazelnut) Aerial Spray 0.3579 NS NS NS 0.9543 10 62719-442 (1)

Filbert (hazelnut) Ground Spray 0.3579 NS NS NS 0.9543 10 62719-442 (1)

### Page 36 of 45 Use Site Aerial and/or Ground Application Identified by Equipment/Lab

el Restriction Application Method Type Desc Maximum Single Application Rate (lb/acre) Max # Apps /

CC A. I. Max App Rate/CC (lb/acre) Max # Apps / Year A. I. Max App Rate/Ye

ar (lb/acre) Minimum Retreatment

Interval

(days) Registration Numbers

Fruiting Vegetables Aerial Spray 0.2386 NS NS NS 0.9543 7 62719-442 (1)

Fruiting Vegetables Ground Spray 0.2386 NS NS NS 0.9543 7 62719-442 (1)

Grapes Aerial Spray 0.2386 NS NS NS 0.7157 10 62719-442 (1)

Grapes Ground Spray 0.2386 NS NS NS 0.7157 10 62719-442 (1)

Grass forage/fodd

er/hay Aerial Spray 0.1193 NS NS NS 0.4771 NS 62719-442 (1)

Grass forage/fodd

er/hay Ground Spray 0.1193 NS NS NS 0.4771 NS 62719-442 (1)

Guava Aerial Spray 0.2386 NS NS NS 0.9543 6 62719-442 (1)

Guava Ground Spray 0.2386 NS NS NS 0.9543 6 62719-442 (1)

Jaboticaba Aerial Spray 0.2386 NS NS NS 0.9543 6 62719-442 (1)

Jaboticaba Ground Spray 0.2386 NS NS NS 0.9543 6 62719-442 (1)

Java Apple Aerial Spray 0.2386 NS NS NS 0.9543 6 62719-442 (1)

Java Apple Ground Spray 0.2386 NS NS NS 0.9543 6 62719-442 (1)

Leafy Vegetables Aerial Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)

Leafy Vegetables Ground Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)

Legume Vegetables Aerial Spray 0.2386 NS NS 4/YR 0.9543 7 62719-442 (1)

Legume Vegetables Ground Spray 0.2386 NS NS 4/YR 0.9543 7 62719-442 (1)

Lime, Spanish Aerial Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)

Lime, Spanish Ground Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)

Litchi Nut Aerial Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)

Litchi Nut Ground Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)

Longan Aerial Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)

Longan Ground Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)

Mamey (Mammee

Apple) Aerial Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)

Mamey (Mammee

Apple) Ground Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)

### Page 37 of 45 Use Site Aerial and/or Ground Application Identified by Equipment/Lab

el Restriction Application Method Type Desc Maximum Single Application Rate (lb/acre) Max # Apps /

CC A. I. Max App Rate/CC (lb/acre) Max # Apps / Year A. I. Max App Rate/Ye

ar (lb/acre) Minimum Retreatment

Interval

(days) Registration Numbers

Mango Aerial Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)

Mango Ground Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)
Mint/Peppe

rmint/ Spearmint Aerial Spray 0.2386 NS NS NS 0.9543 14 62719-442 (1)

Mint/Peppe

rmint/ Spearmint Ground Spray 0.2386 NS NS NS 0.9543 14 62719-442 (1)

Non Grass Forage/Fod der/Straw/

Hay Aerial Spray 0.1193 NS NS NS 0.4771 NS 62719-442 (1)

Non Grass Forage/Fod der/Straw/

Hay Ground Spray 0.1193 NS NS NS 0.4771 NS 62719-442 (1)

Okra Aerial Spray 0.2386 NS NS NS 0.9543 7 62719-442 (1)

Okra Ground Spray 0.2386 NS NS NS 0.9543 7 62719-442 (1)

Onions (green) Aerial Spray 0.1789 NS NS NS 0.9543 10 62719-442 (1)

Onions (green) Ground Spray 0.1789 NS NS NS 0.9543 10 62719-442 (1)

Ornamental

and/or shade trees Aerial Spray 0.2386 NS NS NS 0.4771 10 62719-442 (1)

Ornamental

and/or shade trees Ground Chemigation 0.2386 NS NS NS 0.4771 10 62719-442 (1)

Ornamental

and/or shade trees Ground Spray 0.2386 NS NS NS 0.4771 10 62719-442 (1)

Ornamental Herbaceous

Plants Aerial Spray 0.2386 NS NS NS 0.4771 10 62719-442 (1)

Ornamental Herbaceous

Plants Ground Chemigation 0.2386 NS NS NS 0.4771 10 62719-442 (1)

Ornamental Herbaceous

Plants Ground Spray 0.2386 NS NS NS 0.4771 10 62719-442 (1)

Ornamental Nonfloweri ng Plants Aerial Spray 0.2386 NS NS NS 0.4771 10 62719-442 (1)

Ornamental Nonfloweri ng Plants Ground Chemigation 0.2386 NS NS NS 0.4771 10 62719-442 (1)

Ornamental Nonfloweri ng Plants Ground Spray 0.2386 NS NS NS 0.4771 10 62719-442 (1)

Ornamental

Woody Shrubs and

vines Aerial Spray 0.2386 NS NS NS 0.4771 10 62719-442 (1)

Ornamental

Woody Ground Chemigation 0.2386 NS NS NS 0.4771 10 62719-442 (1)

### Page 38 of 45 Use Site Aerial and/or Ground Application Identified by Equipment/Lab

el Restriction Application Method Type Desc Maximum Single Application Rate (lb/acre) Max # Apps /

CC A. I. Max App Rate/CC (lb/acre) Max # Apps / Year A. I. Max App Rate/Ye

ar (lb/acre) Minimum Retreatment

Interval

(days) Registration Numbers

Shrubs and

vines

Ornamental

Woody Shrubs and

vines Ground Spray 0.2386 NS NS NS 0.4771 10 62719-442 (1)

Papaya Aerial Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)

Papaya Ground Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)

Passion

Fruti (granadilla) Aerial Spray 0.2386 NS NS NS 0.9543 6 62719-442 (1)

Passion

Fruti (granadilla) Ground Spray 0.2386 NS NS NS 0.9543 6 62719-442 (1)

Peanuts (unspecifie d) Aerial Spray 0.1491 NS NS 3/YR 0.9543 7 62719-442 (1)

Peanuts (unspecifie d) Ground Spray 0.1491 NS NS 3/YR 0.9543 7 62719-442 (1)

Pecan Aerial Spray 0.2386 NS NS NS 0.9543 14 62719-442 (1)

Pecan Ground Spray 0.2386 NS NS NS 0.9543 14 62719-442 (1)

Pistachio Aerial Spray 0.3579 NS NS NS 0.9543 10 62719-442 (1)

Pistachio Ground Spray 0.3579 NS NS NS 0.9543 10 62719-442 (1)

Pome Fruits Aerial Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)

Pome Fruits Aerial Spray 0.3 00 NS 1 NS NS 10 62719-438 (1)

Pome Fruits Ground Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)

Pome Fruits Ground Spray 0.3 00 NS 1 NS NS 10 62719-438 (1)

Pomegranat

e Aerial Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)

Pomegranat

e Ground Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)

Pulasan Aerial Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)

Pulasan Ground Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)

Radish Aerial Spray 0.2386 NS NS NS 0.4771 14 62719-442 (1)

Radish Ground Spray 0.2386 NS NS NS 0.4771 14 62719-442 (1)

Rambutan Aerial Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)

### Page 39 of 45 Use Site Aerial and/or Ground Application Identified by Equipment/Lab

el Restriction Application Method Type Desc Maximum Single Application Rate (lb/acre) Max # Apps /

CC A. I. Max App Rate/CC (lb/acre) Max # Apps / Year A. I. Max App Rate/Ye

ar (lb/acre) Minimum Retreatment

Interval

(days) Registration Numbers

Rambutan Ground Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)

Root and

Tuber Vegetables Aerial Spray 0.1491 NS NS 3/YR 0.9543 14 62719-442 (1)

Root and

Tuber Vegetables Aerial Spray 0.2386 NS NS NS 0.9543 14 62719-442 (1)

Root and

Tuber Vegetables Ground Spray 0.1491 NS NS 3/YR 0.9543 14 62719-442 (1)

Root and

Tuber Vegetables Ground Spray 0.2386 NS NS NS 0.9543 14 62719-442 (1)

Sapodilla Aerial Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)

Sapodilla Ground Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)
Soybeand (unspecifie d) Aerial Spray 0.1193 NS NS 4/YR 0.9543 NS 62719-442 (1)

Soybeand (unspecifie d) Ground Spray 0.1193 NS NS 4/YR 0.9543 NS 62719-442 (1)

Star Apple Aerial Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)

Star Apple Ground Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)

Stone Fruits Aerial Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)

Stone Fruits Ground Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)

Strawberry Aerial Spray 0.1789 NS NS NS 0.9543 10 62719-442 (1)

Strawberry Ground Spray 0.1789 NS NS NS 0.9543 10 62719-442 (1)

Sugar Beet Aerial Low volume
spray (concentrate) 0.2386 NS NS NS 0.9543 14 WY120005 (1)

Sugar Beet Aerial Spray 0.2386 NS NS NS 0.9543 14 62719-442 (1)

Sugar Beet Ground Spray 0.2386 NS NS NS 0.9543 14 62719-442 (1)

Sweet Potato Aerial Spray 0.1491 1 0.1491 NS NS NS CA060026 (1)

Sweet Potato Aerial Spray 0.1491 3 0.4473 NS NS NS MS060014,N C060003 (2)

Sweet Potato Ground Spray 0.1491 1 0.1491 NS NS NS CA060026 (1)

Sweet Potato Ground Spray 0.1491 3 0.4473 NS NS NS MS060014,N C060003 (2)

Tree Nuts Aerial Spray 0.3579 NS NS NS 0.9543 10 62719-442 (1)

### Page 40 of 45 Use Site Aerial and/or Ground Application Identified by Equipment/Lab

el Restriction Application Method Type Desc Maximum Single Application Rate (lb/acre) Max # Apps /

CC A. I. Max App Rate/CC (lb/acre) Max # Apps / Year A. I. Max App Rate/Ye

ar (lb/acre) Minimum Retreatment

Interval

(days) Registration Numbers

Tree Nuts Ground Spray 0.3579 NS NS NS 0.9543 10 62719-442 (1)

Turnip Greens Ground Spray 0.2386 NS NS NS 0.9543 10 62719-442 (1)

Walnut (english/bla ck) Aerial Spray 0.3579 NS NS NS 0.9543 10 62719-442 (1)

Walnut (english/bla ck) Ground Spray 0.3579 NS NS NS 0.9543 10 62719-442 (1)

### Page 41 of 45 

## APPENDIX C. Output from OPP EIIS In cident Database for Methoxyfenozide

### Page 42 of 45 

## APPENDIX D. STIR Results for Evaluate Pote ntial for Inhalation Risk to Birds and Mammals

Screening Tool for Inhalation Risk This tool is designed to provide the risk assesso r with a rapid method for determining the potential significance of the inhalation exposure route to birds and mammals in a risk assessment.

Input

Application and Chemical Information

Enter Chemical Name Methoxyfenozide
Enter Chemical Use Is the Application a Sp ray? (enter y or n) y If Spray What Type (enter ground or air) ground Enter Chemical Molecular Weight (g/mole) 368 Enter Chemical Vapor Pressure (mmHg) 2.00E-08 Enter Application Rate (lb a.i./acre) 0.25

Toxicity Properties

Bird
Enter Lowest Bird Oral LD 50 (mg/kg bw) 2250 Enter Mineau Scaling Factor 1.15 Enter Tested Bird Weight (kg) 0.178
Mammal
Enter Lowest Rat Oral LD 50 (mg/kg bw) 2000
Enter Lowest Rat Inhalation LC 50 (mg/L) 4.5 Duration of Rat Inhalation Study (hrs) 4 Enter Rat Weight (kg) 0.35

Output
Results Avian (0.020 kg ) Maximum Vapor Concentration in Air at Saturation (mg/m 3 ) 3.96E-04 Maximum 1-hour Vapor Inhalation Dose (mg/kg) 4.98E-05 Adjusted Inhalation LD 50 2.82E+01 Ratio of Vapor Dose to Adjusted Inhalation LD 50 1.76E-06 Exposure not Likely Significant Maximum Post-treatment Spra y Inhalation Dose (mg/kg) 2.64E-02 Ratio of Droplet Inhalation Dose to Adjusted Inhalation LD 50 9.36E-04 Exposure not Likely Significant

Results Mammalian (0.015 kg ) Maximum Vapor Concentration in Air at Saturation (mg/m 3 ) 3.96E-04 Maximum 1-hour Vapor Inhalation Dose (mg/kg) 6.26E-05 Adjusted Inhalation LD 50 2.68E+02 Ratio of Vapor Dose to Adjusted Inhalation LD 50 2.34E-07 Exposure not Likely Significant Maximum Post-treatment Spra y Inhalation Dose (mg/kg) 3.32E-02

### Page 43 of 45 Ratio of Droplet Inhalation Dose to Adjusted Inhalation LD 50 1.24E-04 Exposure not Likely Significant

### Page 44 of 45 

## APPENDIX E. SIP Results for Evaluate Potential Risk to Birds and Mammals from Drinking Water Exposure.

Table 1. Inputs Parameter Value Chemical name Methoxyfenozide Solubility (in water at 25 o 

### C; mg/L) 3.3

Mammalian LD 50 

### (mg/kg-bw) 2000 Mammalian test species laboratory rat Body weight (g) of "other" mammalian species

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

Avian LD 50 

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

Mallard NOAEC (mg/kg-diet) 1000 Bobwhite quail NOAEC (mg/kg-diet) 1000 NOAEC (mg/kg-diet) for other bird species Body weight (g) of other avian species NOAEC (mg/kg-diet) for 2nd other bird species Body weight (g) of 2nd other avian species

Table 2. Mammalian Results Parameter Acute Chronic Upper bound exposure (mg/kg-bw) 0.5676 0.5676 Adjusted toxicity value (mg/kg-bw) 1538.3211 153.8321 Ratio of exposure to toxicity 0.0004 0.0037

Conclusion* Drinking water exposure alone is NOT a potential

concern for mammals Drinking water exposure alone is NOT a potential

concern for mammals

Table 3. Avian Results Parameter Acute Chronic Upper bound exposure (mg/kg-bw) 2.6730 2.6730 Adjusted toxicity value (mg/kg-bw) 1620.9664 49.6126 Ratio of exposure to acute toxicity 0.0016 0.0539

### Page 45 of 45 Conclusion* Drinking water exposure alone is NOT a potential concern for birds Drinking water exposure alone is NOT a potential concern for birds

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