1

OFFICE OF CHEMICAL 

SAFETY AND 

POLLUTION 

PREVENTION

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON D.C., 20460

 

PC Code: 121027

DP Barcode: 427543

Date: September 16, 2015

MEMORANDUM

SUBJECT: Registration Review: Preliminary Environmental Fate and Ecological Risk 

Assessment Endangered Species Effects Determination for Methoxyfenozide

TO: Bonnie Adler, Chemical Review Manager

Jill Bloom, Team Leader

Linda Arrington, Branch Chief

Risk Management and Implementation Branch V

Pesticide Re-evaluation Division (7508P)

FROM: Mary Clock-Rust, Biologist 

Karen Milians, Ph.D., Chemist

Environmental Risk Branch IV

Environmental Fate and Effects Division (7507P)

REVIEWED

BY: Thomas Steeger, Ph.D., Senior Science Advisor

Jim Carleton, Ph.D., Senior Scientist

Environmental Risk Branch IV

Environmental Fate and Effects Division (7507P)

APPROVED

BY: Jean Holmes, DVM, MPH, Branch Chief

Environmental Risk Branch IV

Environmental Fate and Effects Division (7507P)

The Environmental Fate and Effects Division (EFED) has completed a preliminary risk assessment 

for the insecticide methoxyfenozide. EFED’s analysis has determined that the use of 

methoxyfenozide has the potential for direct effects on Federally listed threatened/endangered 

(hereafter referred to as “listed”) and non-listed freshwater invertebrates following acute exposure, 

and on listed and non-listed freshwater and estuarine/marine invertebrates following chronic 

exposure. Acute risk to listed estuarine/marine invertebrates is also possible for the majority of 

methoxyfenozide uses evaluated. The likelihood of direct adverse effects on birds, terrestrial-phase 

amphibians, reptiles, mammals, fish, aquatic-phase amphibians, and terrestrial and aquatic plants 
2

from exposure to methoxyfenozide as a result of the registered uses is expected to be low. 

However, the extent to which other taxa that depend on aquatic invertebrate species may be 

indirectly affected is uncertain. Finally, data are incomplete but available lines of evidence suggest 

that methoxyfenozide risk to terrestrial and aquatic plants is likely to be low.

The potential for direct adverse effects to adult honey bees (Apis mellifera) is considered low. A 

review of submitted field studies on honey bee brood development and colony survival (including 

overwintering) does not indicate that honey bee brood (larvae/pupae) are adversely affected by 

exposure to the compound, although uncertainties were noted in the submitted toxicity data. A 

recently submitted laboratory-based acute toxicity study on larval honey bees raises new concerns. 

Using the new toxicity data combined with default exposure and larval food consumption rates 

from the Guidance for Assessing Pesticide Risks to Bees (US EPA, 2014) results in risk estimates 

that exceed EFED’s levels of concern (LOC) for honey bee larvae. 

Uncertainties

Although methoxyfenozide is intended to act specifically on immature stages of insects within the 

order Lepidoptera (moths/butterflies), there is uncertainty about the extent to which larval stages 

of other insects (excluding honey bees) may be affected, since the compound acts as an ecdysone 

agonist and is intended to induce premature molts thereby resulting in death of the target organism.

There are also concerns for beneficial lepidopterans that co-occur in areas where methoxyfenozide 

is used.

No data are available to assess the potential for adverse effects on terrestrial plants or to aquatic 

vascular plants from exposure to methoxyfenozide; however, toxicity data available for aquatic 

non-vascular plants did not indicate any adverse effects from exposure up to the solubility limit of 

the compound (3.3 mg/L). Also, terrestrial and vascular aquatic plant data on tebufenozide, 

another ecdysone agonist in the same chemical class as methoxyfenozide, suggest that 

methoxyfenozide toxicity to terrestrial and aquatic plants is likely to be low. Further, no reports of 

plant damage resulting from exposure to methoxyfenozide have been recorded in EFED’s incident 

databases. Given the mode of action of these compounds, it is uncertain whether any analogous 

pathways (i.e., ecdysone receptors) exist in plants.

For uses where the retreatment interval (RTI) was not specified, a three-day interval was assumed. 

The RTI was not specified on two labels, EPA Reg, # 62719-442 (corn) and EPA Reg. # 62719-

666 (peanuts).

Although whole colony studies are available for methoxyfenozide and did not demonstate any 

consistent long-term adverse effects on brood development, a laboratory-based chronic toxicity

study with larval honey bees, in which exposure conditions can be more readily controlled, would 

increase the confidence in risk conclusions and help to address uncertainties regarding repeated 

direct exposure of larvae to methoxyfenozide. Specifically, a 21-day larval honey bee toxicity 

study extending through adult emergence would be informative. 
3

OFFICE OF CHEMICAL 

SAFETY AND POLLUTION 

PREVENTION

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON D.C., 20460

Environmental Fate and Ecological Risk Assessment for 

Registration Review of Methoxyfenozide.

Methoxyfenozide

CAS Registry No: 161050-58-4 PC Code: 121027

Prepared by:

Mary Clock-Rust, Biologist

Karen Milians, Ph.D., Chemist

U.S. Environmental Protection Agency

Office of Pesticide Programs

Environmental Fate and Effects Division

Environmental Risk Branch IV

1200 Pennsylvania Ave., NW

Mail Code 7507P

Washington, DC 20460

Reviewed by:

Jean Holmes D.V.M, Branch Chief 

Thomas Steeger, Ph.D., Senior Science Advisor

Jim Carleton, Ph.D., Senior Scientist

September 16, 2015
4

Executive Summary

The preliminary risk assessment (PRA) in support of Registration Review for methoxyfenozide, 

examines the risks to wildlife associated with the compound’s labeled uses. The risk assessment 

is based on the best available scientific and commercial information on the use, environmental fate 

and transport, and ecological effects of methoxyfenozide on non-target organisms.

Methoxyfenozide is a dibenzoyl hydrazine insecticide which acts as an insect growth regulator

(IGR) and registered for use on a variety of agricultural as well as non-agricultural sites across the 

US. The chemical is an agonist for the invertebrate molting hormone, ecdysone, and induces a 

precocious incomplete molt in invertebrates, particularly lepidopterans (butterflies/moths). 

Methoxyfenozide may be applied using ground, aerial, conventional spray or chemigation 

application methods. Single application rates range from 0.16 lb a.i./A (for cotton and peanuts) to 

a maximum of 0.40 lb a.i./A (for cotton). Use sites include citrus, cotton, fruiting vegetables (Crop 

Group 1B), globe artichokes, bushberries (Crop Group 13-07B), corn, peanuts, grapes, stone fruits 

(Crop Group 12-12) and tree nuts (Crop Group 14-12; including almonds, walnuts, and other nuts). 

Annual maximum application rates across all methoxyfenozide use sites do not exceed 1.0 lb 

a.i./acre/year. The technical registrant for this pesticide is Dow AgroSciences (DAS). 

The compound is considered very persistent and moderately mobile based on a soil aerobic 

metabolism half-lives range from 336 to 1100 days; organic carbon partition coefficient (Koc)

range from 219 to 922 mL/goc; and, a log octanol-water partition coefficient (Kow) of 3.72. Once 

applied, methoxyfenozide has the potential to move off the site of application by leaching, erosion 

and runoff where it can accumulate in aquatic systems.

While methoxyfenozide is expected to persist in the environment and move to surface water via 

runoff and erosion based on laboratory studies, a monitoring study was recently completed which

showed no apparent accumulation of methoxyfenozide in sediment and water at any of the

monitoring sites under the conditions tested. Furthermore, bioconcentration data with both fish 

and invertebrates indicate that the compound does not bioconcentrate appreciably (BCF range: 1.1 

– 22.1X) and it depurates relatively quickly once organisms are no longer exposed. Available data 

indicate that for both freshwater and estuarine/marine fish, the toxicity of methoxyfenozide 

appears limited by its solubility in water (3.3 mg a.i./L) and at this concentration, no adverse effects 

(i.e., mortality or sublethal effects) were observed on fish following acute exposure.

EFED’s analysis has determined that all of the registered uses of methoxyfenozide have the 

potential to result in direct adverse effects to freshwater and estuarine/marine invertebrates. 

Specifically, federally listed threatened/endangered (hereafter referred to as “listed”) and nonlisted freshwater invertebrates are at risk following acute exposure to methoxyfenozide, and listed 

and non-listed aquatic freshwater and estuarine/marine invertebrates following chronic exposure.

Acute risk to listed estuarine/marine invertebrates is also possible for the majority of registered 

methoxyfenozide use sites that are in close proximity to these environments. A low likelihood of 

direct adverse effects to birds, terrestrial-phase amphibians, reptiles, mammals, fish, aquatic-phase 

amphibians, and terrestrial and aquatic plants is expected from exposure to methoxyfenozide as a 
5

result of the registered uses. However, there is the potential for indirect effects on taxa that depend 

on aquatic invertebrate species for prey and/or habitat, although the magnitude and likelihood of 

indirect effects are uncertain.

There are data to indicate that lepidopteran species of terrestrial invertebrates are sensitive to 

methoxyfenozide, consistent methoxyfenozide’s use in controlling lepidopteran pests (such as the 

corn root worm, cabbage moth, diamond back moth). While available acute toxicity data do not 

indicate potential risk to adult honey bees, a laboratory-based study indicates that larval honey 

bees may be sensitive to methoxyfenozide following a single (acute) exposure. Screening-level 

risk quotient (RQ) values exceed the acute risk level of concern (LOC) for honey bee larvae, 

although refined RQ values based on measured residue levels in pollen/nectar are below the acute 

risk LOC. Field-based studies of whole colonies fed methoxyfenozide-spiked diets did not exhibit 

any consistent, long-term adverse effect on brood development and/or colony overwintering 

capacity. Laboratory-based chronic toxicity data for larval honey bees would increase the 

confidence in risk conclusions and address uncertainties about methoxyfenozide risk to terrestrial 

invertebrates and lead to more robust risk conclusions. Specifically, a 21-day larval bee toxicity 

study extending through adult emergence would help to address uncertainties. 

1.0 Problem Formulation

The problem formulation sets the objectives for the risk assessment and provides a plan for 

analyzing the data and characterizing the risk (USEPA 1998a). EFED completed the preliminary 

problem formulation for the environmental fate, ecological risk, endangered species, and drinking 

water exposure assessments to be conducted as part of the Registration Review of 

methoxyfenozide (USEPA, 2013b). 

The following section summarizes the key points of that document and discusses any differences 

between the analysis outlined in the preliminary problem formulation and the analysis conducted 

in this risk assessment. 

1.1 Nature of Regulatory Action

The risk assessment is conducted as part of the Agency’s Registration Review process for pesticide 

active ingredients. The Registration Review process was established under the Food Quality 

Protection Act (FQPA 1996).

2. Nature of Chemical Stressor

Methoxyfenozide, 3-methoxy-2-methylbenzoic acid 2-(3,5-dimethylbenzoyl)-2-(1,1-

dimethylethyl)hydrazide (CAS No. 161050-58-4), belongs to the diacylhydrazine class of 

insecticides that interfere with the binding of the endogenous steroidal molting hormone 20-

hydroxyecdysone with its nuclear receptor protein complex. As such, methoxyfenozide is referred 

to as an ecdysteroid (ecdysone) agonist1

. Exposure of sensitive organisms (pests including fruit

worm, diamond back moth, corn root worm, leaf roller, armyworm, grapevine moth and other 

 1 Shimizu et al., 1997.
6

members of the Order Lepidoptera) to the compound induces a precocious incomplete molt and 

leads to the death of the organism. 

This assessment evaluates potential risks to non-target species resulting from the use of 

methoxyfenozide products containing 22.6%, 80.0%, 23.3%, and 20.6% methoxyfenozide and 

correspond to the EPA Registration Numbers 62719-442, 62719-438, 62719-666 and 62719-667, 

respectively.

2.2. Overview of Pesticide Usage

Data for usage was provided by OPP’s Biological and Economic Analysis Division (BEAD) and

is derived from USDA National Agricultural Statistics Service (NASS; 2003-2010), private 

pesticide market research (2003-2010), and the California Department of Pesticide Regulation 

(2003-2010)2

. The top use sites treated with methoxyfenozide are almonds (50,000 lbs per year), 

grapes (30,000 lbs per year), apples, lettuce, tomatoes (20,000 lbs per year), pistachios (10,000 lbs 

per year) and cotton (7,000 lbs per year). 

Based on the submitted labels, the maximum single application rate for methoxyfenozide is 0.40

lb a.i./acre (for cotton), and the maximum yearly rate is 1.0 lb a.i./A (EPA Reg. # 62719-438, see

Appendix A). Intrepid® can be applied by ground or aerial application equipment to most of the 

crops for which it is registered (except citrus). Two end-use products (EPA Reg. No. 62719-666

and 62719-667) contains methoxyfenozide (28.3% and 20.6 %) combined with spinetoram and 

spinosad (5.66% and 10.3%, respectively). A summary of use information for methoxyfenozide 

for all registered products can be found in Appendix A.

2.3 Receptors

2.3.1 Aquatic and Terrestrial Effects

In ecological risk assessment, a receptor is a biological entity that is exposed to a stressor, in this 

case a pesticide (USEPA, 1998). Consistent with the process described in the Overview Document 

(USEPA, 2004), this risk assessment uses a surrogate species approach in its evaluation of 

methoxyfenozide. Toxicity data generated using surrogate test species, which are intended to be 

representative of broad taxonomic groups, are used to infer potential effects on a variety of species 

(receptors) included under these broader taxonomic groupings. Table 1 provides the general 

taxonomic groups and surrogate species tested to evaluate potential ecological effects of 

methoxyfenozide to broad classes of non-target organisms. Within each of these taxonomic 

groups, a measure of effect is selected from among the available test data. 

Acute and chronic toxicity data from studies submitted by pesticide registrants along with the 

available open literature are used to evaluate potential direct effects of methoxyfenozide on aquatic 

and terrestrial receptors. The open literature studies are located through EPA’s database ECOTOX 

 2 US EPA, 2012a. 
7

(http://cfpub.epa.gov/ecotox/), which provides a source for locating single chemical toxicity data 

for aquatic life, terrestrial plants, and wildlife. 

Table 1: Taxonomic Groups and Test Species Evaluated for Assessing Potential Ecological 

Effects of Methoxyfenozide.

Organismal Group Typical Test Species

Birds1 Mallard duck (Anas platyrhynchos)

Bobwhite quail (Colinus virginianus)

Passerine (not available)

Mammals Norway rat (Rattus norvegicus)

Terrestrial invertebrates Honey bee (Apis mellifera L.)

Freshwater fish2 Bluegill sunfish (Lepomis macrochirus)

Rainbow trout (Oncorhynchus mykiss)

Fathead minnow (Pimephales promelas)

Freshwater invertebrates Water flea (Daphnia magna)

Midge (Chironomus riparius)

Estuarine/marine fish Sheepshead minnow (Cyprinodon variegatus)

Estuarine/marine invertebrates Mysid (Americamysis bahia)

Eastern oyster (Crassostrea virginica)

Terrestrial plants3 Monocots – Crop species, such as corn (Zea mays)

Dicots – Crop Species, such as soybean (Glycine max)

Aquatic plants and algae Duckweed (Lemna gibba) 

Freshwater Algae (Pseudokirchneriella subcapitata) 1 Birds are surrogates for terrestrial-phase amphibians and reptiles. 2 Freshwater fish are surrogates for aquatic-phase amphibians. 3 Four species of two families of monocots, one of which is corn; six species of at least four dicot families, one of which is soybeans.

2.3.2 Ecosystems Potentially at Risk

The ecosystems at risk are often extensive in scope; therefore, it may not be possible to identify 

specific ecosystems at the screening level. In general terms, terrestrial ecosystems potentially at 

risk could include treated sites and areas immediately adjacent to treated sites that may receive 

drift, runoff, erosion, or discharged groundwater. Such areas could include cultivated fields, 

fencerows, hedgerows, meadows, fallow fields or grasslands, woodlands, wetlands, riparian zones, 

and other uncultivated areas. 

Aquatic ecosystems potentially at risk include water bodies adjacent to or downstream from treated 

areas, and can include lentic systems, i.e., ponds, lakes and impoundments (reservoirs), and lotic 

systems (streams and rivers). Aquatic ecosystems supplied by groundwater, including cave 

ecosystems and areas supplied by seeps and springs, may be at risk from compounds that leach

into the subsurface. For uses in coastal areas, aquatic habitat at potential risk includes marine and 

estuarine ecosystems. In evaluating aquatic exposure within water bodies, EFED considers the 

water column, benthic sediment, and pore water to all be compartments of potential concern. 

2.4 Assessment Endpoints

Assessment endpoints represent the actual environmental values that are to be protected, defined 

by an ecological entity (species, community, or other entity) and its attribute or characteristics 

(USEPA 1998). For methoxyfenozide, the ecological entities include the following: birds, 
8

amphibians, reptiles, mammals, freshwater fish and invertebrates, estuarine/marine fish and 

invertebrates, terrestrial plants, insects, and aquatic plants and algae. The attributes assessed for 

each of these entities may include growth, survival, and reproduction. (See Section 2.6 Analysis 

Plan, for further discussion).

The assessment endpoints are intended to reflect individual and population sustainability and 

community structure within ecosystems and hence relate back to ecosystems at risk. If risks are 

expected for given species/taxa based on the screening-level assessment, then risks might be 

expected to translate to higher levels of biological organization.

2.5 Conceptual Model

The conceptual model used to depict the potential ecological risk associated with the proposed and 

existing uses of methoxyfenozide relies on previous assessments and the Agency’s current 

understanding of the environmental fate and ecological effects of the chemical. Consistent with 

the intended use of methoxyfenozide as an insect growth regulator, potential risk to non-target 

terrestrial and aquatic invertebrates is expected. Effects on invertebrates, which represent the 

primary consumers in an ecosystem, may result in secondary effects on other consumers. The 

conceptual model assumes that methoxyfenozide is capable of directly and/or indirectly affecting 

terrestrial vertebrates and invertebrates and aquatic vertebrates and invertebrates, provided that 

environmental concentrations are sufficiently elevated as a result of proposed and existing uses.

As described in the preliminary Problem Formulation3

, there is potential for adverse effects to 

listed and non-listed freshwater and estuarine/marine aquatic invertebrates following acute and/or 

chronic exposure to methoxyfenozide. Also, there is uncertainty regarding the potential effects of 

methoxyfenozide on larval development of terrestrial invertebrates. Direct adverse effects to birds, 

mammals, fish, and terrestrial and aquatic plants are not expected; however, given the potential 

for effects on aquatic invertebrate species, indirect effects to animals and plants are possible. 

2.5.1 Risk Hypothesis

For methoxyfenozide, the following ecological risk hypothesis is employed for the ecological risk 

assessment:

Given the existing uses of methoxyfenozide and its environmental fate properties, there is

possible acute and chronic exposure to non-target aquatic and terrestrial organisms. 

When used in accordance with the label, methoxyfenozide may result in adverse effects 

upon the survival, growth, and reproduction of non-target aquatic and terrestrial and 

animals. 

 

 3 US EPA, 2013.
9

2.6 Analysis Plan

2.6.1. Measures of Exposure 

2.6.1.1 Measures of Aquatic Exposure 

Measures of exposure to aquatic animals and plants are pesticide concentrations in surface water 

and benthic sediment pore water simulated by the Surface Water Concentration Calculator 

(SWCC) to generate estimated environmental concentrations (EECs) of methoxyfenozide that may 

occur from use on crops, typically at maximum label use rates. The EECs used in risk assessment 

are simulated 1-in-10 year return frequency “peaks” (acute) and mean concentrations over a 

specified duration (chronic) generated at the modeled site, which is selected to represent a location 

expected to be more contamination-vulnerable than most locations where the crop is grown. 

2.6.1.2 Measures of Terrestrial Exposure

Terrestrial wildlife are potentially exposed to methoxyfenozide via consumption of residues on 

food items from spray applications on agricultural uses. For spray applications, the T-REX model 

(Terrestrial Residue EXposure model; v. 1.5.2; June 6, 2013b) is used to predict dietary exposure 

to methoxyfenozide residues on foliar surfaces and insects using the Kenaga nomogram as 

modified by Fletcher (Hoerger and Kenaga, 1972; Fletcher et al., 1994). In this assessment, the 

default foliar dissipation half-life of 35 days was used for terrestrial modeling purposes. An 

example printout of the T-REX model output is provided in Appendix D. Exposure to terrestrial 

plants was assessed using the TERR-Plant model (version 1.2.2), a tier 1 model used to estimate 

upper-bound terrestrial plant exposure from a single pesticide application. The results of the 

TerrPlant analysis are provided in Appendix E.

Potential exposure pathways through drinking water (imbibition) and inhalation were screened 

using the SIP (Screening Imbibition Program) and STIR (Screening Tool for Inhalation Risk) 

programs, respectively, as noted in the Problem Formulation for methoxyfenozide (US EPA, 

2013b). Results 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). Screening using the STIR model found 

inhalation exposures to be of low concern in birds and mammals, i.e., no LOC exceedances are 

expected via this potential route of exposure. SIP and STIR are described in detail at: 

http://www.epa.gov/oppefed1/models/terrestrial/index.htm.

2.6.2 Measures of Effect

Measures of effect are obtained from a suite of registrant-submitted guideline studies which were 

conducted with a limited number of surrogate test species (Table 1). The test species are not 

intended to be representative of the most sensitive taxa but rather were selected based on their 

ability to thrive under laboratory conditions. Toxicity testing reported in this risk assessment 

utilizes surrogate species to represent all freshwater fish (2000+) and bird (680+) species in the 

U.S. In addition, the ECOTOX database4 was searched in 2014 for more ecological effects data 

 4 US EPA, 2009.
10

for methoxyfenozide. No additional data were available that indicated greater sensitivity than those 

embodied in the registrant-submitted study endpoints.

The acute measures of effect used in this screening-level assessment are the LD50 (Lethal Dose), 

LC50 (Lethal Concentration), EC50 (Effects Concentration), and IC50 (Inhibition Concentration). 

These are measures of acute toxicity which result in 50% of the respective effect in tested 

organisms. The endpoints for chronic measures of exposure are the NOAEC (No Observed 

Adverse Effects Concentration) and the NOAEL (No Observed Adverse Effects Level). Toxicity 

studies were submitted for freshwater fish and invertebrates, estuarine/marine fish and 

invertebrates, aquatic and terrestrial plants, birds, mammals, and honey bees. The endpoints used 

for risk assessment were derived from studies which underwent review and were classified as 

“acceptable” (conducted under guideline conditions and considered to be scientifically valid) or 

“supplemental” (conditions deviated from guidelines but the results are considered to be 

scientifically valid). 

2.6.4 Integration of Exposure and Effects

The exposure and toxicity effects data are integrated in order to evaluate the risks of adverse 

ecological effects on non-target species. For the risk assessment of methoxyfenozide, the risk 

quotient (RQ) method is used to compare estimated exposure and measured toxicity values. The 

RQ method involves dividing the EEC by acute and chronic toxicity values. The resulting RQs 

are then compared to the Agency’s Levels of Concern (LOCs) (USEPA 2004) (Table 2). The

LOCs are used to indicate when applications of methoxyfenozide, as directed on the label, are 

assumed to have the potential to cause adverse effects to non-target organisms.
11

Table 2: Agency Risk Quotient (RQ) Metrics and Levels of Concern (LOC) Per Risk Class.

Risk Class Risk Description RQ LOC

Aquatic Animals (fish and invertebrates)

Acute Potential for effects to non-listed animals from acute 

exposures

Peak EEC/LC501 0.5

Acute 

Restricted Use

Potential for effects to animals from acute exposures

Risks may be mitigated through restricted use classification Peak EEC/LC501 0.1

Acute Listed 

Species

Listed species may be potentially affected by acute 

exposures

Peak EEC/LC501 0.05

Chronic Potential for effects to non-listed and listed animals from 

chronic exposures

60-day EEC/NOAEC 

(fish) 1

21-day EEC/NOAEC 

(invertebrates)

Aquatic Plants

Non-Listed Potential for effects to non-listed plants from exposures Peak EEC/LC501 1

Listed Potential for effects to listed plants from exposures Peak EEC/NOAEC 1

Terrestrial Animals (mammals, birds and invertebrates)

2

Acute Potential for effects to non-listed animals from acute 

exposures

EEC/LC50 (Dietary) 0.5

EEC/LD50 (Dose)

EEC/LD50

(invertebrate) 0.4

Acute 

Restricted Use

Potential for effects to animals from acute exposures

Risks may be mitigated through restricted use classification

EEC/LC50 (Dietary) 0.2

EEC/LD50 (Dose)

Acute Listed 

Species

Listed species may be potentially affected by acute 

exposures

EEC/LC50 (Dietary) 0.1

EEC/LD50 (Dose)

Chronic Potential for effects to non-listed and listed animals from 

chronic exposures EEC/NOAEC 1

Terrestrial and Semi-Aquatic Plants

Non-Listed Potential for effects to non-target, non-listed plants from 

exposures

EEC/EC25 1

Listed Plant Potential for effects to non-target, listed plants from 

exposures

EEC/NOAEC

1

EEC/EC05

1 LC50 or EC50. 2 EEC based on upper bound Kenaga nomogram values for foliar exposure.

3.0 Analysis

3.1 Use Characterization

Based on the submitted labels, the maximum single application rate for methoxyfenozide is 0.06 

lb a.i./acre for cotton, and the maximum yearly rate is 1.0 lb a.i./A (EPA Reg. # 62719-438, Refer 

to Table 3 below). Intrepid® 2F (EPA Reg. # 62719-442) contains 22.6% a.i. and can be applied 

by ground or aerial application equipment. However although cotton has the lowest single 

application rate at 0.06 lbs a.i./A, the maximum number of applications annually or seasonally for 
12

this use is not specified on the label (EPA Reg. # 62719-442). Summary use information for 

methoxyfenozide for all registered products can be found in Appendix A.

Because methoxyfenozide is registered for use on a large number of crops, a representative set of 

use sites was chosen for risk assessment purposes (Table 3). The scenarios modeled in this 

assessment include those that have the highest application rates, as well as those that result in the 

highest environmental exposure concentrations (through either aquatic or terrestrial 

environments). A summary of use information for methoxyfenozide in all registered products can 

be found in Appendix A.

Table 3: Representative Methoxyfenozide Use Sites for Ecological Risk Assessment

Use Site

Single 

Application 

Rate 

(lbs. a.i./A)1

Max. No. of 

Application

s per year

Max. Yearly 

Application 

Rate (lbs. 

a.i./A)

Min. 

Application 

Interval 

(days)

Application 

Method

EPA reg. 

number

Citrus 0.25 4 1 14 Ground 62719-442

Cotton

0.41 4 1 10 Aerial and 

ground 62719-438

0.06 6 1 10 Aerial and 

ground 62719-442

Fruiting 

Vegetable

(Crop Group 

1B)

0.25 4 1 7 Aerial and 

ground 62719-442

Globe 

Artichoke 0.25 4 1 7 Aerial and 

ground 62719-442

Bush Berries

0.06 3 0.75 7 Aerial and 

ground 62719-442

0.25 3 0.75 7 Aerial and 

ground 62719-442

Corn

0.06 17 1 NS2 Aerial and 

ground 62719-442

0.25 4 1 NS2 Aerial and 

ground 62719-442

Peanuts

0.078 3 1 NS2 Aerial and 

ground 62719-666

0.16 3 1

7 Aerial and 

ground 62719-666
13

Use Site

Single 

Application 

Rate 

(lbs. a.i./A)1

Max. No. of 

Application

s per year

Max. Yearly 

Application 

Rate (lbs. 

a.i./A)

Min. 

Application 

Interval 

(days)

Application 

Method

EPA reg. 

number

Grapes

0.12 5 0.75 NS 2 Aerial and 

ground 62719-442

0.234 5 0.75 4 Aerial and 

ground 62719-666

Tree Nuts

(Almonds, 

Pistachios, 

Pecans) 

0.252 4 1 3 Aerial and 

ground 62719-442

0.38 4 1 10 Aerial and 

ground 62719-442

0.12 8 1 8 Aerial and 

ground 62719-442

1

Cotton use presents the maximum and minimum single application rate of all the uses. Only 3 applications were 

assumed for the maximum single application rate of 0.40 lbs a.i./A (0.4 lbs a.i./A x 2 + 0.2 lbs a.i./A). 2 A three day application window was assumed as it was not specified on the labels. 

 

3.2 Exposure Characterization

3.2.1. Environmental Fate Characterization

Methoxyfenozide is non-volatile (based on its Henry’s constant of 1.6 x10-9 atm·m3

·mole-1), 

hydrophobic (based on its octanol-water partition coefficient: log Kow=3.72), and possesses 

moderate water solubility (3.3 mg/L at 25°C). Methoxyfenozide is stable to hydrolysis (at pHs 5, 

7, and 9) and photodegradation on soil. Based on the classification system of Goring et al.5

, 

methoxyfenozide is considered very persistent in soil with aerobic soil half-lives ranging from 336 

to 1,100 days. Aquatic fate studies demonstrate that methoxyfenozide is also persistent in water 

under both aerobic and anaerobic conditions. Two minor (i.e. equivalent to less than 10% of 

applied radioactivity) transformation products (in addition to CO2) formed in fate studies have 

been identified: RH-117236 (3,5-dimethylbenzoic acid N-tert-butyl-N’-(3-hydroxy-2-

methylbenzoyl)hydrazide) and RH-131154 (3-[N-tert-butyl-N’-(3-methoxy-2-methylbenzoyl)-

hydrazinocarbonyl]-5-methylbenzoic acid (see Appendix B for structures). 

Methoxyfenozide is characterized as mobile to moderately mobile according to the Food and 

Agriculture Organization United Nations scale6

, having soil organic carbon partition coefficients 

(Koc) that range from 219 to 922 mL/goc, and soil partition coefficients (Kd) that range from 1.1 to 

6.2 mL/g. Given its resistance to degradation and its mobility, methoxyfenozide has the potential 

to move off the site of application by leaching, runoff and/or movement with eroded sediment, and 

 5 Goring et al., 1975. 6 FAO, 2000.
14

to subsequently accumulate in aquatic systems. Table 4 provides a summary of chemical and

environmental fate properties of methoxyfenozide.

Because of the chemical’s persistence, mobility, and potential to accumulate in aquatic systems, 

the Agency required that a monitoring study 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 would result in accumulation of methoxyfenozide residues in water and/or sediment.

Methoxyfenozide was monitored for a two-year period in two lotic (flowing) water bodies and five 

lentic (standing or ponds) water bodies in each of the following states: California, Mississippi, and 

Michigan and showed no apparent accumulation of methoxyfenozide in sediment at any 

monitoring sites. 

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 DT50s (the amount of time

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 studies, at concentrations up to 0.039 mg/kg soil, 

providing evidence of leaching. Metabolites in these studies were not identified. Thus, results from 

the TFD studies are consistent with those from the laboratory fate studies, suggesting high 

persistence in the terrestrial environment and the potential for leaching to ground water. 

In a bioconcentration study on juvenile bluegill 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. To address lingering uncertainty about the 

chemical’s bioconcentration potential in other aquatic animals, the registrant submitted a 

bioconcentration study using the freshwater clam (Corbicula fluminea). The results of this study 

indicate that methoxyfenozide did not bioconcentrate extensively in invertebrates. When placed in 

untreated water, the clams depurated methoxyfenozide by 95% in roughly 16 days. Although the 

parent compound has a log octanol-water partition coefficient (Kow) of 3.72 and might be expected 

to bioconcentrate, the relatively low measured BCF coupled with the rapid depuration of the 

compound suggests that methoxyfenozide is metabolized in fish and clams to more polar 

compounds and readily excreted.

Table 4: Chemical Properties and Environmental Fate Parameters of Methoxyfenozide.

Parameter Value Description Reference

Chemical Classification Diacylhydrazine --

Molecular Formula C22H28N2O3 --

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

--
15

Parameter Value Description Reference

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 25oC Moderately soluble

Vapor pressure (25oC) 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, Kow

5248 (log Kow = 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

t1/2= 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 in water 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

t1/2 = 1100 days (loamy sand) Persistent

Studies exhibited poor 

extraction of the solid 

phase and/or loss of 14C 

over time.

MRID 446178-07

t1/2 = 336 and 722 days in loamy sand and 

sandy clay loam, respectively. MRID 446178-08

t1/2 = 573 days (loam soil) MRID 441444-32

Anaerobic aquatic 

metabolism t1/2= 654 days

Persistent

Poor extraction, and 

redox and pH 

information was not 

submitted

MRID 446178-10

Aerobic aquatic 

metabolism

t1/2 = 963 days and 387 days in aerobic 

flooded sandy loam and clay soils, 

respectively

Persistent MRID 446178-09

Field Dissipation

Terrestrial field 

dissipation

t1/2= 327 days (sand soil, WA) Persistent MRID 446178-11

t1/2= 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 36 

inches)

MRID 446178-12
16

Parameter Value Description Reference

Mobility

Leaching and 

absorption/desorption

Koc and Kd 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 moderately

mobile

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

AR=Applied Radioactivity

Classification of persistency was based on Goring scale, 1975. 

Mobility was described using Swann et al. scale, 1983.

t1/2=Half-life

3.2.1.1 Residues of Concern

The only residue of concern at this time is the parent chemical, methoxyfenozide. The predominant 

degradates of methoxyfenozide are RH-117236 and RH-131154 (See Appendix B for structures), 

however these were found only in low relative amounts (1 – 6.7% of applied radioactivity) in the 

environmental fate studies.

3.2.2 Measures of Aquatic Exposure

3.2.2.1 Model Inputs

The EECs for surface water were generated using the Surface Water Concentration Calculator 

(SWCC v. 1.106). Table 5 list the input parameters used in aquatic exposure modeling for 

methoxyfenozide. 

Chemical property model input values were chosen in accordance with EFED’s current input 

parameter guidance7

. The upper 90% confidence limit on the mean half-life (960 d) was selected 

to represent aerobic soil metabolism in SWCC and the mean Koc value was used. Methoxyfenozide 

was modeled as stable to both hydrolysis and photolysis. The upper 90% confidence limit on the 

mean half-life (1,559 d) was selected to represent aerobic aquatic metabolism.

Table 5: SWCC Input Parameter Values for Methoxyfenozide Uses1

Input Parameter Value Source Comment

Organic Carbon Partition 

Coefficient (Koc) (L/kgoc) 490 MRID 441444-33 Represents the average Koc.

Aerobic Soil Metabolism 

Half-life (days) 960

MRIDs 446178-08, 

446178-07, 441444-

32

Represents the 90 percent confidence 

bound on the mean half-life.

 7 US EPA, 2009.
17

Input Parameter Value Source Comment

Aerobic Aquatic 

Metabolism Half-life 

(days)

1559 MRID 446178-09 Represents the 90 percent confidence 

bound on the mean half-life.

Anaerobic Aquatic 

Metabolism Half-life 

(days)

1962 MRID 446178-10

Input value is 3X the measured half-life 

to account for uncertainty in using a 

single data point

Hydrolysis Half-lives 

(days) 0 MRID 441444-30 Stable

Aqueous Photolysis

Half-life (days) 0 MRID 446178-05 Stable

1 Parameters are selected as per Guidance for Selecting Input Parameters in Modeling the Environmental Fate and Transport of 

Pesticides; Version 2.1, October 22, 2009.

Although there is little evidence of potential bioaccumulation of methoxyfenozide in aquatic 

organisms8, because methoxyfenozide has a log Kow of 3.72, an additional exposure pathway that 

is considered in this assessment is the consumption of contaminated fish or aquatic invertebrates 

that have residues of methoxyfenozide from uptake from the water and diet. The potential risk 

from this pathway is evaluated and discussed further in the “Risk Description” section of the 

document. Multiple lines of evidence will be used to evaluate bioaccumulation potential, including 

measured bioconcentration factors (BCF), bioaccumulation factors (BAF) and a food web

bioaccumulation model (KABAM9

, the Kow-Based Aquatic Bioaccumulation Model). The 

bioaccumulation assessment relies on predicted water and sediment concentrations from SWCC 

to estimate concentrations of methoxyfenozide in the tissues of aquatic organisms. In order to 

evaluate potential risk, these estimated tissue concentrations will be compared to toxicity values 

for various taxonomic groups that may consume aquatic organisms. The current version of 

KABAM estimates risks only to terrestrial birds and mammals consuming aquatic prey. 

3.2.2.2 Selection of Crops and Scenarios

Fifteen standard scenarios were used in the modeling uses: Florida (FL) citrus, Mississippi (MS) 

cotton, North Carolina (NC) cotton, California (CA) almonds, FL tomato, FL pepper, CA lettuce, 

Georgia (GA) pecans, New York (NY) grapes, MS corn, NC peanut, Oregon (OR) berries OP, FL 

turf, and OR grass seed (Table 6). Aerial application was used for each of the modeling scenarios

because it results in more conservative estimates; however, for citrus, ground application was 

modeled since aerial applications are not permitted. Application rates and retreatment intervals

were obtained from the Intrepid® 2F label10 (Table 6). The retreatment interval represents the 

minimum amount of time allowed between pesticide reapplications. For uses where the retreatment 

interval was not specified, a three day interval was assumed. The application dates for these 

scenarios were chosen according to their crop profiles, crop lifecycle and/or time when heavy pest 

pressure is likely to occur11 (Table 6).

 8 In a bioaccumulation study with juvenile bluegill sunfish (Lepomis macrochirus), BCFs 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. 9 http://www.epa.gov/oppefed1/models/water/kabam/kabam_user_guide.html

10 Intrepid Master Label, 2013. 11 USDA Crop Profiles. Available online at: http://www.ipmcenters.org/cropprofiles/CP_form.cfm
18

The CA lettuce scenario was used as a proxy in modeling the globe artichoke use, because globe 

artichokes are grown almost exclusively in California, and specifically in the Monterey area where 

CA lettuce is grown. The application rate of 0.25 lbs a.i./acre as well as the retreatment interval of 

seven days were obtained from the label. There is no standard scenario for use on bushberries;

therefore, the OR berries OP (organophosphate) scenario was used because it provides the closest 

approximation to bushberries among the approved scenarios. The application dates for the 

scenarios were chosen according to their crop profiles, crop lifecycle and/or time when heavy pest

pressure was likely to appear. The highest application rates for methoxyfenozide were assessed, 

which represent both the Intrepid® 2F label and Intrepid® 80 WSP (water soluble pouch). 

Environmental fate-related input values were chosen for modeling, in accordance with current 

input parameter guidance12. The upper 90% confidence bound on the mean was selected for the 

aerobic soil metabolism half-life (960 days) input for surface water, as per current input parameter 

guidance for this model. Hydrolysis and photolysis were modeled as stable. The upper 90% 

confidence bound on the mean was selected for the aerobic aquatic metabolism half-life (1559 

days) input, and 3 times the single available anaerobic aquatic metabolism half-life was used to 

represent degradation occurring within the benthic sediments. 

Table 6: SWCC Application-Specific Input Parameters for Methoxyfenozide. 

Uses PRZM 

Scenario

Max App 

rate (lbs 

ai/A)

# Apps Interval

(days)

% Drift/ 

Efficiency

Date of 1st of 

application

Citrus FL citrus 0.25 4 14 0.062/0.99 April 1st

Cotton1

NC cotton 0.40 3 10 0.125/0.95 July 18th

NC cotton 0.40 3 10 0.125/0.95 July 18th

MS cotton 0.40 3 10 0.125/0.95 July 18th

Fruiting 

vegetables

FL tomato 0.25 4 7 0.125/0.95 April 1st

FL pepper 0.25 4 7 0.125/0.95 April 1st

Globe 

Artichoke

CA lettuce 0.25 4 7 0.125/0.95 April 16th

CA lettuce 0.25 4 7 0.125/0.95 April 16th

Bushberries

OR berries 0.06 3 7 0.125/0.95 March 24th

OR berries 0.25 3 7 0.125/0.95 March 24th

Grass, forage 

fodder hay

OR Grass seed 0.07 8 3 assumed 0.125/0.95 July 18th

FL turf 0.07 8 3 assumed 0.125/0.95 July 18th

Peanuts NC peanut 0.078 3 3 assumed 0.125/0.95 Aug 16th

NC peanut 0.16 3 7 0.125/0.95 Aug 16th

 12 US EPA, 2009.
19

Uses PRZM 

Scenario

Max App 

rate (lbs 

ai/A)

# Apps Interval

(days)

% Drift/ 

Efficiency

Date of 1st of 

application

Corn2 MS corn 0.06 17 Assumed 3 assumed 0.125/0.95 Jun 10

MS corn 0.25 4 Assumed 3 assumed 0.125/0.95 Jun 10

Grapes2 NY Grapes 0.12 5 3 assumed 0.125/0.95 May 22nd

NY Grapes 0.234 5 4 0.125/0.95 May 22nd

Tree nuts 

Crop group 

14 (Almond, 

pistachios)

CA almond 0.25 4 3 0.125/0.95 July 16th

CA almond 0.38 4 10 0.125/0.95 July 16th

GA Pecans 0.12 8 8 0.125/0.95 May 1st

1

Cotton use presents the maximum and minimum single application rate of all the uses. Only 3 applications were 

assumed for the maximum single application rate of 0.40 lbs a.i./A (0.4 lbs a.i./A x 2 + 0.2 lbs a.i./A). 2 Interval was not specified therefore, a 3 days interval was assumed. Although methoxyfenozide is not registered for 

use on grapes in NY, this scenario was used for modeling purposes.

3.2.2.3 Surface Water

The methoxyfenozide surface water EECs for representative use sites are listed below in Table 7.

The highest EECs were for cotton, with an acute (peak) value of 185 μg/L (parts per billion; ppb)

and chronic values slightly lower than this. (Note that because methoxyfenozide is persistent to 

degradation, concentrations increase year over year in the modeled farm pond. If use of 

methoxyfenozide is discontinuous over a 30 year period of simulation, EECs can be expected to 

be less than those reported).

Table 7: Estimated Surface Water Environmental Concentrations (EECs) for Current Uses 

of Methoxyfenozide.

USE SCENARIO 

(PRZM scenario used; rate 

modeled in kg/ha)

Estimated Environmental Concentrations (EECs, ppb)

Application 

Method Peak 96-hour 21-day 60-day

Citrus

FL citrus; 0.28 x 

4 applic. @ 14-d 

interval 

ground 22.7 22.6 22.4 22.1

Cotton1

NC cotton; 0.45 

x 2 (applic.)+ 

0.22 x 1 applic. 

@ 10-d interval

aerial 185 185 183 182

NC cotton; 0.07 

x 6 (applic.) @ 

10-d interval

aerial 48.4 48.3 47.8 47.4

MS cotton; 0.45 

x 2 (applic.)+ 

0.22 x 1 applic. 

@ 10-d interval

aerial 120 119 118 117

Fruiting 

Vegetables

FL tomato, 0.28 

x 4 applic @ 7-d 

interval

aerial 119 119 118 116

FL pepper, 0.28 

x 4 applic @ 7-d 

interval

aerial 135 134 133 130
20

USE SCENARIO 

(PRZM scenario used; rate 

modeled in kg/ha)

Estimated Environmental Concentrations (EECs, ppb)

Application 

Method Peak 96-hour 21-day 60-day

Globe 

Artichoke

CA lettuce, 0.28 

x 4 applic @ 7-d 

interval

aerial 144 144 143 142

Grass, 

forage 

fodder hay

OR Grass seed x 

8 applic @ 3-d 

interval

aerial 37.4 37.3 37.1 36.7

FL turf, 0.07 x 8 

applic @ 3-d 

interval

aerial 20.5 20.4 20.2 19.9

Bushberries

OR berries, 0.07 

x 3 applic @ 7-d 

interval

aerial 13.2 13.1 13.0 12.9

OR berries, 0.28 

x 3 applic @ 7-d 

interval

aerial 52.7 52.6 52.2 51.6

Peanuts

NC peanuts, 0.09 

x 3 applic @ 3-d 

interval

aerial 27.6 27.6 27.4 27.0

NC peanuts, 0.18 

x 3 applic @ 7-d 

interval

aerial 54.5 54.4 54.0 53.4

Corn 

MS corn, 0.07 x 

17 applic @ 3-d 

interval

aerial 144 144 143 141

MS corn, 0.28 x 

4 applic @ 3-d 

interval

aerial 130 130 127 127

Grapes2

NY grapes, 0.13 

x 5 applic @ 3-d 

interval

aerial 63.9 63.8 63.5 63.1

NY grapes, 0.26 

x 5 applic @ 4-d 

interval

aerial 141 141 140 139

Tree nuts

(almond, 

pistachio)

CA almond, 0.25 

x 4 applic @ 3-d 

interval

aerial 66.0 65.8 65.3 64.3

CA almond, 0.43 

x 4 applic @ 10-

d interval

aerial 101 101 100 99

GA pecans, 0.13 

x 8 applic @ 8-d 

interval

aerial 72.3 72.1 71.7 70.7

1Refer to the modeling results for NC cotton scenario in Appendix F 2 Although methoxyfenozide is not registered for use on grapes in NY, this scenario was used for modeling purposes.

Bolded value represents the highest EDWC for methoxyfenozide

3.2.2.4 Aquatic Exposure Monitoring 

Methoxyfenozide was not included in monitoring conducted by the U. S. Geological Survey 

(USGS) National Water Quality Assessment (NAWQA) program nor in the California Department 

of Pesticide Regulation (CDPR) Surface Water Database (CDPR 2003). 
21

Because methoxyfenozide is very persistent, moderately mobile and may accumulate in the aquatic

environment following repeated applications, the Agency recommended surface water and 

sediment studies using a representative sample of water bodies in high use areas (based on DAS 

record sales, growers and state and county government records). These studies were intended to 

determine whether multiple years of use would result in evidence of accumulation of 

methoxyfenozide residues in water and/or sediment in areas that represent vulnerable fields (prone 

to runoff). Samples for determining methoxyfenozide residues were collected over a two-year 

period (2012 and 2013) in two lotic (flowing) water bodies and five lentic (standing) water bodies 

in each of the following states: California, Mississippi, and Michigan.

The maximum concentration of methoxyfenozide detected in lotic surface water samples was 1.31 

μg/L, found in Mississippi. The maximum concentration detected in lentic waters was 0.845 μg/L,

in a pond in Michigan. The maximum concentration of methoxyfenozide in benthic sediments (31 

μg/kg) was detected in Michigan. No apparent accumulation of methoxyfenozide was observed in 

sediment at any monitoring sites after years of use. There are deficiencies of the monitoring study 

such as analytical methods slightly modified (ECMs reported in the study differed from the one 

submitted to the Agency) and one sampling site was changed with an alternate sampling point. 

It may not be appropriate to make a direct comparison from the results of the monitoring study

with the values obtained in modeling (using SWCC) because the frequency of sampling in the 

monitoring study may not have captured the peak concentration. Additionally, SWCC model 

simulates the impact of daily weather on the treated agricultural field, and resulting concentrations 

in an adjacent farm pond over a defined period (here, thirty years). During this time, pesticide is 

washed-off of the field into the water-body by twenty to forty rainfall/runoff events per year. Each 

new addition of pesticide mass from each runoff event adds to the existing pesticide mass in the 

pond from previous runoff and/or spray-drift events. Since methoxyfenozide is known to be 

persistent in aquatic environments, the mass of the pesticide accumulates in the pond from one 

year to the next. In the SWCC model, the yearly simulated peaks are not independent of each other 

but are temporally auto-correlated, meaning that the “1-in-10 year EECs” obtained from model 

post-processing are in part functions of the simulation duration. As a result, SWCC results likely 

overestimate concentrations in streams and various other kinds of water bodies, as over the course 

of thirty years, some loss of methoxyfenozide is expected due to washout, dispersion, burial of 

sediment and other dissipative processes that aren’t simulated. In particular, methoxyfenozide 

concentrations in lotic (flowing) water bodies are not expected to accumulate at such a high 

concentrations from year to year because of downstream advective removal. Table 8 below details 

the results of the monitoring study conducted by DAS. 

Table 8: Summary of the Methoxyfenozide Sediment and Surface Water Monitoring Study 

Site

Concentration of methoxyfenozide in 

surface water (μg/L), (Number of samples 

analyzed)

Concentration of methoxyfenozide in 

sediment (μg/kg), (Number of samples 

analyzed)

Lotic Lentic Lotic Lentic

California ND-1.01 (88)1 ND-0.0502 (20) ND (8) ND (20)

Mississippi ND-1.31 (55)2 ND-0.233 (20) ND (8) ND (20)
22

Michigan ND (36)3 ND-0.845 (23) ND (4) ND-31.0 (23)

LOQ=0.050 μg/L and LOD= 0.015μg/L in surface water and LOD= 3 μg/kg in sediment. 

ND =below detection limit

1

87, 7- day composite samples and 1, 28-day composite sample 2

47, 7- day composite samples and 8, 28-day composite samples 3

22, 7- day composite samples and 14, 28-day composite samples

OPP is not aware of any other monitoring programs in which methoxyfenozide is an analyte.

3.2.3 Measures of Terrestrial Exposure

Exposure to terrestrial organisms was assessed based on the registered uses of methoxyfenozide. 

Dietary exposure to birds and mammals was assessed using the T-REX model2. Terrestrial plant 

exposure was estimated using the TerrPlant model13.

3.2.3.1. Ingestion of Foliar Residues by Birds and Mammals

Terrestrial wildlife exposure estimates are typically calculated for the dietary exposure of birds 

and mammals. Avian exposures are considered surrogates for exposures to terrestrial-phase 

amphibians and reptiles. For exposure to terrestrial organisms, such as birds and mammals, 

pesticide residues on food items are estimated, based on the assumption that organisms are exposed 

to pesticide residues in a given exposure use pattern. For methoxyfenozide, application methods 

for the registered uses include aerial, broadcast, banded, and directed spray of liquid formulations 

for all crops. 

T-REX14 (Version 1.5.2) is used to calculate upper-bound dietary EECs for estimating exposure 

to birds and mammals resulting from the registered uses of methoxyfenozide. A one year time 

period is simulated, and the default foliar dissipation half-life of 35 days was used for modeling 

the registered uses. An example printout from the T-REX model is provided in Appendix D. 

Table 9: Input Parameters for Deriving Terrestrial EECs for Methoxyfenozide Labeled 

Uses (T-REX).

Use Site Application Rate 

(lbs a.i./A)

Minimum Reapplication 

Interval (days)1 Number of Applications

Citrus 0.25 14 4

Cotton3 0.4 10 4

Fruiting Vegetables 0.25 7 4

Globe Artichokes 0.25 7 4

Bushberries 0.25 7 3

Corn 0.25 NS2 4

Peanuts 0.16 7 3

 13 http://www.epa.gov/oppefed1/models/terrestrial/index.htm 14 USEPA. 2014. T-REX Version 1.5.2 (Terrestrial Residue Exposure). http://www.epa.gov/oppefed1/models/terrestrial/#trex

(last accessed 02.24/15)
23

Use Site Application Rate 

(lbs a.i./A)

Minimum Reapplication 

Interval (days)1 Number of Applications

Grapes 0.234 4 5

Tree Nuts 0.38 10 4

1 TREX v 1.5.2 allows for the input of applications with varying retreatment intervals. Where multiple values are entered, the 

second interval represents an application that occurs outside the growing season, but still presents the potential for exposure.

2 A three-day re-application interval was assumed as it was not specified on the label.

3 For the maximum single application rate of 0.40 lbs a.i./A, two applications of 0.4 lb a.i./acre plus one application of 0.2 lb 

a.i./acre were assumed (0.4 lbs a.i./A x 2 + 0.2 lbs a.i./A).

Differences in exposures between ground and aerial applications are not assessed with the current 

T-REX model. Therefore, terrestrial risk conclusions for the registered uses apply to both ground 

and aerial exposures resulting from application of methoxyfenozide. Dose-based EECs for birds 

and mammals range from a low of 115 mg/kg-bw for exposure to small birds from 

methoxyfenozide use on peanuts to a high of 333 mg/kg-bw for exposure to small birds from use 

on tree nuts. Dietary EECs for birds and mammals range from a low of 6.31 mg/kg diet for 

fruits/pods/seeds from methoxyfenozide use on peanuts to a high of 292 mg/kg diet for short grass 

from use on cotton (Table 10). Uncertainties in the terrestrial EECs are primarily associated with 

a lack of data on pesticide spray interception and subsequent dissipation from foliar surfaces. An 

example of output from the T-REX model is provided in Appendix C.

Table 10: T-REX Calculated EECs as Food Residues for Terrestrial Animals from 

Methoxyfenozide Labeled Uses.

Food Type

Dietary 

Based

(ppm)

(mammals 

and birds)

Dose Based

(mg/kg-bw)

(birds)

Dose Based

(mg/kg-bw)

(mammals)

All Size 

Classes

Small

(20 g)

Medium

(100 g)

Large

(1000 g)

Small

(15 g)

Medium

(35 g)

Large

(1000 g)

Citrus

(4 appl.@ 0.25 lb a.i./acre, 14-day RTI, 1 lb a.i./acre/year)

Herbivores/Insectivores

Short grass 166 189 108 48.3 158 109 25.4

Tall grass 76.1 86.7 49.4 22.1 72.6 50.1 11.6

Broadleaf plants 93.4 106 60.6 27.2 89.1 61.6 14.3

Fruits/pods/seeds 10.4 11.8 6.7 3.0 10.0 6.8 1.59

Arthropods 65.0 74.0 42.2 18.9 62.0 42.9 9.94

Granivores

Seeds N/A 2.63 1.50 0.67 2.20 1.52 0.35

Cotton

(3 appl. (2@0.4 lb a.i./acre+1@0.2 lb a.i./acre), 10-day RTI, 1 lb a.i./acre/year)

Herbivores/Insectivores

Short grass 292 333 190 85.0 279 193 44.7

Tall grass 134 153 87.0 39.0 128 88.3 20.5

Broadleaf plants 164 187 107 47.8 157 108 25.1

Fruits/pods/seeds 18.3 20.8 11.9 5.31 17.4 12.0 2.79

Arthropods 115 130 74.4 33.3 109 75.5 17.5

Granivores

Seeds N/A 4.62 2.64 1.18 3.87 2.68 0.62

Fruiting Vegetables, Globe Artichokes

(4 appl. @0.25 lb a.i./acre, 7-day RTI, 1 lb a.i./acre/year)
24

Food Type

Dietary 

Based

(ppm)

(mammals 

and birds)

Dose Based

(mg/kg-bw)

(birds)

Dose Based

(mg/kg-bw)

(mammals)

All Size 

Classes

Small

(20 g)

Medium

(100 g)

Large

(1000 g)

Small

(15 g)

Medium

(35 g)

Large

(1000 g)

Herbivores/Insectivores

Short grass 197 225 128 57.4 188 130 30.1

Tall grass 90 103 58.7 26.3 86.2 596 13.8

Broadleaf plants 111 126 72.1 32.3 106 73.1 17.0

Fruits/pods/seeds 12.3 14.0 8.01 3.59 11.8 8.13 1.88

Arthropods 77.3 88.0 50.2 22.5 73.7 50.9 11.8

Granivores

Seeds N/A 3.12 1.78 0.80 2.61 1.81 0.42

Bushberries

(3 appl. @0.25 lb a.i./acre, 7-day RTI, 0.75 lb a.i./acre/year)

Herbivores/Insectivores

Short grass 158 180 102 45.9 150 104 24.1

Tall grass 72.3 82.3 46.9 21.0 68.9 47.6 11.0

Broadleaf plants 88.7 101 57.6 25.8 84.6 58.5 13.6

Fruits/pods/seeds 9.86 11.2 6.40 2.87 9.40 6.49 1.51

Arthropods 61.8 70.4 40.1 18.0 58.9 40.7 9.44

Granivores

Seeds N/A 2.49 1.42 0.64 2.09 1.44 0.33

Peanuts

(3 appl. @0.16 lb a.i./acre, 7-day RTI, 1 lb a.i./acre/year)

Herbivores/Insectivores

Short grass 101 115 65.6 29.4 96.2 66.5 15.4

Tall grass 46.3 52.7 30.0 13.5 44.1 30.5 7.07

Broadleaf plants 56.8 64.7 36.9 16.5 54.1 37.4 8.67

Fruits/pods/seeds 6.31 7.18 4.10 1.83 6.01 4.16 0.96

Arthropods 39.5 45.0 25.7 11.5 37.7 26.1 6.04

Granivores

Seeds N/A 1.60 0.91 0.41 1.34 0.92 0.21

Corn

(4 appl. @0.25 lb a.i./acre, 3-day RTI1, 1 lb a.i./acre/year)

Herbivores/Insectivores

Short grass 220 251 143 64.0 210 145 33.6

Tall grass 101 115 65.5 29.3 96.1 66.5 15.4

Broadleaf plants 124 141 80.4 36.0 118 81.6 18.9

Fruits/pods/seeds 13.8 15.7 8.93 4.00 13.1 9.06 2.10

Arthropods 86.2 98.1 56.0 25.1 82.2 56.8 13.2

Granivores

Seeds N/A 3.48 1.98 0.89 2.91 2.01 0.47

Grapes

(4 appl: 3@0.234 lb a.i./acre+1@0.05 lb a.i./acre, 4-day RTI, 0.75 lb a.i./acre/year)

Herbivores/Insectivores

Short grass 156.10 177.78 101.38 45.39 148.82 102.86 23.85

Tall grass 71.54 81.48 46.46 20.80 68.21 47.14 10.93

Broadleaf plants 87.80 100.00 57.02 25.53 83.71 57.86 13.41

Fruits/pods/seeds 9.76 11.11 6.34 2.84 9.30 6.43 1.49

Arthropods 61.14 69.63 39.71 17.78 58.29 40.29 9.34

Granivores

Seeds N/A 2.47 1.41 0.63 2.07 1.43 0.33
25

Food Type

Dietary 

Based

(ppm)

(mammals 

and birds)

Dose Based

(mg/kg-bw)

(birds)

Dose Based

(mg/kg-bw)

(mammals)

All Size 

Classes

Small

(20 g)

Medium

(100 g)

Large

(1000 g)

Small

(15 g)

Medium

(35 g)

Large

(1000 g)

Tree Nuts

(3 appl: 2@0.38 lb a.i./acre+1@0.24 lb a.i./acre, 10-day RTI, 1 lb a.i./acre/year)

Herbivores/Insectivores

Short grass 193.79 220.70 125.86 56.35 184.76 127.70 29.61

Tall grass 88.82 101.16 57.68 25.83 84.68 58.53 13.57

Broadleaf plants 109.01 124.15 70.79 31.70 103.93 71.83 16.65

Fruits/pods/seeds 12.11 13.79 7.87 3.52 11.55 7.98 1.85

Arthropods 75.90 86.44 49.29 22.07 72.36 50.01 11.60

Granivores

Seeds N/A 3.07 1.75 0.78 2.57 1.77 0.41

1. RTI=Retreatment interval (days)

2. RTI not stated on label, therefore, a 3-day RTI was assumed.

3.2.3.2. Exposure to Terrestrial Invertebrates

A study of methoxyfenozide residues in honey bee colonies following treatment of almond trees 

with methoxyfenozide was submitted by the registrant and has been reviewed. In this study

consisting of two trials, almond trees in full bloom were treated with the methoxyfenozide 

formulated product Intrepid® 240 SC (24% a.i., no longer registered) in order to quantify residue

levels of methoxyfenozide in pollen, nectar, and larval honey bees (MRID 48962202).

Specifically, the study measured methoxyfenozide levels in pollen and nectar collected by bees, 

present inside larvae, and in pollen and nectar from almond flowers following an application of 

Intrepid® 240 SC while bees were actively foraging. Residue levels in royal jelly, wax and honey 

were not measured. The results indicate that when applied at a rate of 0.19 lb a.i./acre (roughly 

half the maximum application rate of 0.38 lb a.i./acre for tree nuts), residues of methoxyfenozide 

were measured in bee-collected pollen (corbicular pollen) at up to 9.42 mg a.i./kg (ppm); residues 

in nectar (collected from the honey stomachs of forager bees) were roughly an order of magnitude 

lower (i.e., maximum detected was 0.794 mg a.i./kg) than what was detected in pollen. Residues 

were also detected in developing brood and ranged from <0.005 to 0.021 mg a.i./kg. Compared to 

peak residues measured in corbicular pollen on the day of application, residues at 12 days after 

application had declined by 19-fold in Trial 1 and 636-fold in Trial 2. In both trials, residues in 

comb pollen peaked on Day 1 after treatment; by 19 days after treatment, residues in comb pollen 

had declined by a factor of 101-fold in Trial 1 and by a factor of 1.2 in Trial 2. The difference in 

the extent of decline measured in the two studies may be associated with the differences in pollen 

tree strains used combined with the differences in weather at the two sites.

3.2.3.3. Residues in Aquatic Food Items for Mammals and Birds 

The KABAM model (KOW (based) Aquatic BioAccumulation Model) version 1.0 was used to 

evaluate the potential exposure and risk of direct effects to birds and mammals via 

bioaccumulation and biomagnification in aquatic food webs. KABAM is used to estimate 
26

potential bioaccumulation of hydrophobic organic pesticides in freshwater aquatic ecosystems and 

risks to mammals and birds consuming aquatic organisms which have bioaccumulated these 

pesticides. The bioaccumulation portion of KABAM is based upon work by Arnot and Gobas 

(2004) who parameterized a bioaccumulation model based on PCBs and some pesticides (e.g., 

lindane, DDT) in freshwater aquatic ecosystems (Arnot and Gobas, 2004). KABAM relies on a 

chemical's octanol-water partition coefficient (KOW) to estimate uptake and elimination constants 

through respiration and diet of organisms in different trophic levels. Pesticide tissue residues are 

calculated for organisms at different levels of an aquatic food web. The model then uses pesticide 

tissue concentrations in aquatic animals to estimate dose- and dietary-based exposures and 

associated risks to mammals and birds (surrogate for amphibians and reptiles) consuming aquatic 

organisms. Seven different trophic levels including phytoplankton, zooplankton, benthic 

invertebrates, filter feeders, small-sized (juvenile) forage fish, medium-sized forage fish, and 

larger piscivorus fish, are used to represent an aquatic food web. Importantly, chemical 

metabolism by biota is assumed to be zero in KABAM unless evidence indicates such metabolism 

is likely to affect the model predictions substantially. Measured BCF values are lower than what 

would be expected based on methoxyfenozide’s log KOW of 3.72. Input scenarios and parameters 

were chosen to represent the range of exposures from high to low and are presented in Table 11. 

An example output from the bioaccumulation model is provided in Appendix G.

Table 11. Bioaccumulation Model Input Values for Methoxyfenozide.

Parameter Input Value Source

Pesticide Name Methoxyfenozide --

Log KOW 3.72 USEPA, 2000

KOC 490 Mean KOC value from MRID 44144433. 

Pore water EEC 

(μg/L) 181 Maximum 1-in-10 year 21-day average value from surface water 

modeling. The estimated time to reach steady state was 93 days.

Water column 

EEC (μg/L) 178

Maximum 1-in-10 year 60-day average value surface water modeling. 

The estimated time to reach steady state was 93 days. Based on the NC 

cotton use scenario (0.45 lb a.i. x 2 (applications)+ 0.22 lb a.i. x 1 

application @ 10-d interval)

Based on KABAM results, estimated concentrations of methoxyfenozide residues in the tissues of 

organisms in the different trophic levels following application on cotton (NC) range from 23,180

to 46,798 mg/kg-tissue (Table 12). The measured bioconcentration potential of methoxyfenozide

in bluegill sunfish viscera was 22.1 L/kg (4.42 mg/kg), and is lower than BCF values estimated in 

KABAM modeling. The maximum BCF from KABAM was 263 L/Kg in the whole fish, 

suggesting that the model yields high-end estimates of residues in fish and that fish may be able to 

metabolize methoxyfenozide.
27

Table 12. Predicted concentrations of methoxyfenozide in aquatic organism tissues at 

different trophic levels (μg/kg).

Use Scenario Phytoplankton Zooplankton Benthic 

Invertebrates

Filter 

Feeders1

Small 

Fish

Medium 

Fish

Large 

Fish

NC Cotton2 43,774 32,147 35,172 23,180 45,566 46,030 46,798

1 Filter feeders include clams, krill, sponges, whales, and many fish and may be vertebrates or invertebrates.

2 NC Application rate: 0.45 lb a.i. x 2 (applications)+ 0.22 lb a.i. x 1 application @ 10-d interval

Because a reliable metabolism rate constant cannot be generated to parameterize KABAM, the 

empirical BCF values for fish were used to estimate methoxyfenozide concentrations in aquatic 

organisms. The empirical bioconcentration factor (BCF) for methoxyfenozide is 263 L/kg for 

whole fish. Maximum 1-in-10-year 60-day average EECs for the scenarios explored for aquatic 

modeling ranged from 12.9-182 μg a.i./L. The estimated concentrations in aquatic organisms 

resulting from this range of EECs are used in combination the measured BCF to bracket the 

potential concentrations of methoxyfenozide in aquatic vertebrate tissues (at steady state). It 

should be noted that tissue concentrations in aquatic vertebrates will likely be limited by toxicity 

of methoxyfenozide to these organisms. For instance, the NOAEC for aquatic vertebrates exposed 

to tribufos is 3.1 μg a.i./L. At the LOAEC (6.3 μg a.i./L), delayed emergence and development 

were observed. Given that we expect a range of sensitivities in different aquatic invertebrates, 

some sensitive aquatic vertebrates would be expected to experience effects at the estimated 

concentrations while less sensitive species could carry residues in tissue without showing effects. 

Assuming EECs of 12.9-182 μg a.i./L and BCF value of 263 L/kg , methoxyfenozide 

concentrations in aquatic vertebrate tissues may range from 3.3 to 48 mg a.i./kg (diet) (BCF x 

EEC = Concentration in fish). 

3.2.3.4 Exposure to Terrestrial Plants

Risk to terrestrial and semi-aquatic plants was estimated using the TerrPlant model (version 1.2.2). 

The model generates EECs for plants residing near a use area that may be exposed via runoff 

and/or spray drift. The EECs are generated from one application at the maximum rate for a 

particular use, and using compound-specific solubility information. Only a single application is 

considered, based upon the assumptions that for plants, toxic effects are likely to manifest shortly 

after an initial exposure, and that subsequent exposures do not contribute to the response. Hence, 

the model estimates EECs based on application rate, solubility, and default assumptions regarding 

drift. For an example model output of TerrPlant, see Appendix E.

3.3 Ecological Effects Characterization

The ecological effects characterization for methoxyfenozide is based upon registrant-submitted 

toxicity data for the technical grade active ingredient (TGAI) and registered methoxyfenozide 

formulations. The ecotoxicity data available for methoxyfenozide at the time the docket opened 

were discussed in a Preliminary Problem Formulation for Registration Review15. Many aquatic 

and terrestrial organism toxicity studies have been submitted since the Preliminary Problem 

 15 US EPA, 2013.
28

Formulation was completed and are included in this assessment. The most sensitive endpoints used 

for risk assessment are summarized briefly in Sections 3.3.1 and 3.3.2. 

A search of the ECOTOX database in 2014 yielded no new data from suitable studies with more 

sensitive toxicity endpoints than those obtained from registrant-submitted guideline studies 

described below. Appendix C provides a full listing of the ecological effect data that have been 

submitted for methoxyfenozide.

3.3.1 Aquatic Effects Characterization

Based on the most sensitive toxicity endpoints, methoxyfenozide is classified as moderately toxic 

to estuarine/marine invertebrates and as very highly toxic to freshwater invertebrates on an acute 

exposure basis (Table 13). With freshwater and estuarine/marine fish (and aquatic-phase 

amphibians, for which freshwater fish serve as surrogates), the acute toxicity endpoint is nondefinitive (i.e., “>” value) and is close to the limit of solubility. This suggests that the potential 

acute toxicity of methoxyfenozide to these taxa is limited by the chemical’s solubility (3.3 mg/L 

at 25o

C). 

The midge (Chironomus riparius), a freshwater benthic invertebrate, was the most sensitive 

species tested on a chronic exposure basis, and manifested delayed emergence and development 

of the species (at the LOAEC of 0.0063 mg a.i./L (mean measured pore water concentration). Only 

45% of the midges emerged, and these developed more slowly than controls. 

Toxicity data show adverse effects on survival in freshwater fish exposed to methoxyfenozide on 

a chronic exposure basis. Chronic toxicity data in fish indicate that freshwater fathead minnow,

Pimephales promelas, (NOAEC=0.53 mg a.i./L based on survival) are more sensitive to 

methoxyfenozide than the estuarine/marine sheepshead minnow, Cyprinodon variegatus, 

(NOAEC=1.5 mg a.i./L based on growth). Since no acute toxicity data are available for midge 

larvae, an acute-to-chronic ratio (ACR) was used to calculate an acute freshwater invertebrate 

endpoint using acute and chronic toxicity data from another aquatic invertebrate, i.e., the

freshwater waterflea (Daphnia magnia)

16. This results in an estimated EC50 of 0.06 mg a.i./L for 

the midge17.

It is noteworthy however, that measured concentrations (5% of nominal concentrations) in the 

sediment on Day 28 ranged from 90 to 381% of the nominal concentration with an average of 

276% of nominal. Thus, exposure is difficult to quantify and larvae may not have been exposed to 

the full nominal value over the course of the study.

The registrant-submitted data examining the effects of chronic exposure to methoxyfenozide on 

the development of African clawed frogs (Xenopus laevis) in response to uncertainties regarding 

 16 The most sensitive acute and chronic endpoints available for Daphnia are an EC50 of 3.7 mg a.i./L (MRID 

441444-11) and a NOAEC of 0.20 mg a.i./L (MRID 446177-14), respectively. 17 Acute-to-Chronic Ratio (ACR) was used to estimate the acute toxicity for the midge using the ratio of acute to 

chronic data points 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) = (0.06 mg a.i./L)/(0.0031 mg a.i./L)] 
29

potential impacts of the chemical on the hypothalamic-pituitary-thyroid axis (HPT). Based on the 

lack of effects on developmental biomarkers or thyroid histology, methoxyfenozide did not appear 

to affect the development of Xenopus laevis up to 0.0747 mg a.i./L (the highest concentration used 

in the amphibian metamorphosis assay).

The freshwater green algae (Pseudokirchneriella subcapitata) was the most sensitive aquatic nonvascular plant tested, but the endpoint was non-definitive, i.e., the effect concentration for 50% 

mortality of the algae exceeded the highest concentration tested (EC50>3.4 mg a.i./L), suggesting 

that the chemical’s solubility limits its impacts on aquatic non-vascular plants. Data on the effects 

of methoxyfenozide on aquatic vascular plants are not available. In comparison, aquatic plant data 

for tebufenozide, a compound in the same chemical family as methoxyfenozide, are available. Like 

methoxyfenozide, tebufenozide is also a dibenzoyl hydrazine which acts as invertebrate hormone 

analog (ecdysone agonists); both compounds are intended to induce precocious molting and 

subsequent death in target pests (specifically in Lepidoptera). Tebufenozide had no significant 

effect on vascular aquatic plant survival or growth in a seven-day static-renewal test with 

duckweed (Lemna gibba) or in a 96-hour nonvascular aquatic plant toxicity test with green algae 

(P. subcapitata).

For estuarine/marine invertebrates, acute data on Eastern oysters (Crassostrea virginica) indicate 

a 96-hour EC50 of 1.2 mg a.i./L (shell deposition study) which classifies methoxyfenozide as 

moderately toxic on an acute exposure basis. Chronic toxicity data for methoxyfenozide are 

available for an estuarine/marine crustacean, i.e., the mysid shrimp (Americamysis bahia). In this 

study, reduced growth (length) occurred, with a NOAEC of 0.025 mg a.i./L. 

The registrant also submitted data on red swamp crayfish (Procambarus clarkia) to address an

uncertainty regarding whether other economically important aquatic organisms that molt (such as 

other crustaceans) may be sensitive to methoxyfenozide. Exposure of juvenile crayfish to 

methoxyfenozide for 32 days did not affect survival, growth (length or weight), total number of 

molts or number of molts per females in crayfish at any of the test concentrations (EC50: >0.190 

mg a.i./L; NOAEC: 0.190 mg a.i./L;). The study is scientifically sound; however, it is classified 

as supplemental because it is a non-guideline study. Table 13 contains a summary of ecological 

toxicity data for aquatic organisms with the greatest sensitivity to methoxyfenozide. Appendix C

includes all of the reviewed ecological effects data relevant to this action.

Table 13: Summary of the Most Sensitive Endpoints from Aquatic Toxicity Studies for 

Methoxyfenozide

Taxonomic 

Group Study Type Test 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

LC50>4.2 mg a.i./L

(No mortality at the 

highest treatment 

level tested)

Moderately to 

PracticallyNon-Toxic2

441444-10 Acceptable
30

Taxonomic 

Group Study Type Test Species

Toxicity Value

(all units in terms 

of measured active 

ingredient)

Acute 

Toxicity 

Classification

Source 

(MRID) Study Classification

Full Life Cycle 

Toxicity

Fathead minnow

Pimephales 

promelas

NOAEC=0.53 mg 

a.i./L

LOAEC=1.0 mg 

a.i./L (survival)

N/A 446177-16 Acceptable

Freshwater 

Invertebrates

Estimate based on 

Acute-to-Chronic 

Ratio1

Midge

Chironomus 

riparius

EC50 = 0.061 mg 

a.i./L

(mortality)

Very highly 

toxic N/A1 N/A

Chronic Effects on 

Midge Larvae

(28-d)

NOAEC=0.0031 mg 

a.i./L

LOAEC=0.0063 mg 

a.i./L

(Delayed emergence 

and development)

N/A 450328-01 Supplemental

(non-guideline)

Estuarine/ 

Marine Fish

96-Hour Acute 

Toxicity

Sheepshead 

minnow

Cyprinodon 

variegatus

96-hr LC50 >2.8 mg 

a.i./L

Moderately to 

Practically 

Non-Toxic

441444-12 Acceptable

Early Life Stage 

Toxicity

(28-d)

NOAEC = 1.5 mg 

a.i./L

LOAEC = 2.6 mg 

a.i./L

(growth)

N/A 446177-12 Acceptable

Estuarine/ 

Marine 

Invertebrates

96-Hour Shell 

Deposition

Eastern oyster

Crassostrea 

virginica

96-hr EC50 = 1.2 mg 

a.i./L

Moderately 

Toxic 441444-13 Acceptable

Invertebrate Life 

Cycle Toxicity

(28-d)

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

NonVascular 

Aquatic 

Plants

5-Day Toxicity 

Test

Freshwater alga

Pseudokirchnerie

lla subcapitata 

(formerly

Selenastrum 

capricornutum)

EC50 >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 toxicity for the midge using the ratio of acute to chronic data points from studies with 

Daphnia magna and the chronic NOAEC from the midge lifecycle test. [(3.7 mg a.i./L)/(0.20 mg a.i./L) = (0.06 mg a.i./L)/(0.0031 mg a.i./L)] 2 A definitive endpoint was not achieved at or near the solubility limit of methoxyfenozide.
31

3.3.2 Terrestrial Effects Characterization

Methoxyfenozide is classified as practically non-toxic to birds (as well as to reptiles and terrestrialphase amphibians, for which birds serve as surrogates) on both an acute oral and subacute dietary 

exposure basis; the compound is practically non-toxic to mammals on an acute oral exposure basis. 

In a reproductive toxicity study in bobwhite quail (Colinus virginianus), methoxyfenozide was 

associated with a statistically significant decrease in eggshell thickness compared to untreated 

controls (6 % decrease at 780 mg/kg diet). Across the dietary treatment levels of methoxyfenozide 

tested, declines in eggshell thickness were accompanied with increases in the number of eggs 

cracked, although the increase in the number of eggs cracked was not statistically significant. The 

measurement endpoint of eggshell thinning is used to calculate chronic risk to birds (NOAEC=520 

mg/kg-diet; LOAEC =780 mg/kg-diet)). No other effects were observed in chronic toxicity studies

with birds. 

In a 2-generation (1 litter/generation) reproduction study in rats, treatment-related organ and 

histological effects were observed only at 20,000 ppm, the highest dose tested for the parental 

generation. At this dose, increased liver weights were observed in males and females of both 

generations and midzonal to periportal hepatocellular hypertrophy was observed in the livers of 

all males and females of both generations. There were no treatment-related effects on reproductive 

parameters for adult (parent) animals, nor were effects on growth or survival noted. For ecological 

risk assessment purposes, the chronic NOAEL from this study is 20,000 ppm. 

Methoxyfenozide is classified as “practically non-toxic” to adult honey bees (Apis mellifera) on 

both an acute oral and contact exposure basis. The European corn borer (Ostrinia nubilalis), a

lepidopteran target pest, is more sensitive (LC50=0.009 mg/kg-diet18). Although methoxyfenozide 

is intended to target lepidopterans (such as armyworm, cutworms, etc.), there is uncertainty 

regarding the extent to which other orders of insects and taxa dependent on ecdysone may be 

affected. Because of methoxyfenozide’s mode of action, immature insects may be more sensitive 

to methoxyfenozide than are adult insects. 

Based on EPA risk assessment guidance on bees19, two higher-tiered semi-field studies on honey 

bees are available for methoxyfenozide. The semi-field honey bee brood study (MRID 45065501) 

involved feeding adult bees a sucrose syrup containing 101 mg methoxyfenozide/L for 3 weeks. 

In the longer-term colony overwintering study (MRID 48962201) adult bees were fed sucrose

syrup containing methoxyfenozide at concentrations ranging from 6.25-100 mg 

methoxyfenozide/L for 4 days (observation of the bees continued for 300 days). Overall, the 

submitted toxicity data for honey bee colonies suggest that the compound does not adversely affect 

colony brood development and/or overwintering survival, although confounding issues were noted

in the field-based studies with whole colonies. Further, there is uncertainty regarding the extent 

to which the treatment concentrations in the two semi-field studies are representative of those 

resulting from the use of methoxyfenozide at the maximum application rate. 

 18 Trisyono and Chippendale, 1997.

19 USEPA et al. 2014. Guidance for Assessing Pesticide Risks to Bees. Available at: 

http://www2.epa.gov/pollinator-protection/pollinator-risk-assessment-guidance Last accessed 09/16/15.
32

New data on the acute toxicity of methoxyfenozide for larval honey bees were recently submitted 

to the agency under FIFRA Section 6(a)(2)20. The 7-day laboratory-based acute (single dose)

toxicity study with larval honey bees was conducted according to OECD 23721. The design 

consisted of a negative control, five concentrations of methoxyfenozide (ranging from 0.119 μg 

a.i./bee to 40 μg a.i./bee) and a reference substance (dimethoate, PC code 035001). The 7-day 

study resulted in a 72-hour LD50 of 3.69 μg/larvae, although the dose-response curve was initially 

erratic and there were concerns regarding contaminants (chloramphenicol and sulfonamide 

antibiotics) in the royal jelly used to feed developing larvae. In general, mean control (negative 

and solvent) met the OECD study validation criterion of <15% mortality and the study is classified 

as supplemental.

It is unclear why effects were manifested in the laboratory study but not in semi-field, colony-level 

studies. In a real-world setting, as colony-level studies are designed to reflect, the larval diet during 

early stages of development consists largely of royal jelly, a secretion produced by the 

hypopharyngeal glands of the nurse bees. It is possible that the concentration of methoxyfenozide 

in the royal jelly produced in the hive, where adult bees were feed sucrose syrup containing 

methoxyfenozide, was lower in concentration than what was fed directly to the larvae in the 

laboratory-based study. Also, the laboratory-based study involved a single exposure to 

methoxyfenozide while the duration of exposure in the colony-level studies was longer. There 

were confounding issues in both types of studies. Additional laboratory-based toxicity data would 

be useful to resolve whether the toxicity expressed after a single dose is reflected in a longer-term 

repeat-dose study. The 21-day larval toxicity test developed by the Organization for Economic 

Cooperation and Development would provide a means of addressing this uncertainty as it is a 

repeat dose study that extends through adult emergence.

No data are available to assess the effects of methoxyfenozide on terrestrial plants. However,

terrestrial plant toxicity data are available for tebufenozide, another dibenzoyl hydrazine ecdysone 

agonist which acts as an ecdysone agonist. The tebufenozide tier 1 vegetative vigor and seedling 

emergence studies can inform our understanding of the potential toxicity of methoxyfenozide to 

terrestrial plants. 

Tebufenozide resulted in reduced growth (dry weight) in a terrestrial dicotyledonous (dicot) 

species (radish) exposed at 0.97 lb a.i./acre (dry weight reduced by14%) and 1.97 lbs a.i./A (7%) 

in a vegetative vigor study; the effect was statistically significant (p<0.05) at the lowest rate tested 

and a NOAEL was not established (MRID 48533002). Similarly, a NOAEL was not established 

for dicot plants in the seedling emergence test where cabbage emergence was significantly reduced

(p<0.05) by 14% compared to the negative control at the lowest treatment rate of 0.98 lbs a.i./acre

(measured) (MRID 48533001). No other statistically significant effects were observed either 

study. An effect greater than 25% was not observed in either test; therefore the EC25 is greater than 

the highest rate tested.

 20 http://www.epa.gov/pesticides/fifra6a2/ 21 http://www.oecd-ilibrary.org/environment/test-no-237-honey-bee-apis-mellifera-larval-toxicity-test-singleexposure_9789264203723-en
33

Given 1) the mode of action of the compound (insect growth regulator), 2) the available 

information on a similar compound (tebufenozide), and 3) the lack of reported plant incidents for 

methoxyfenozide (see Section 3.3.3 below), the likelihood of adverse effects on terrestrial plants 

from methoxyfenozide is expected to be low.

Table 14 contains a summary of ecological toxicity data for terrestrial organisms with the greatest 

sensitivity to methoxyfenozide.

Table 14: Summary of the Most Sensitive Endpoints from Terrestrial Toxicity Studies for 

Methoxyfenozide

Taxonomic 

Group Study Type Test Species Toxicity Value

Acute 

Toxicity 

Classification

Source 

(MRID) Study Classification

Birds

Acute Oral 

Toxicity

Northern 

bobwhite quail

Colinus 

virginianus

LD50 >2,250 mg 

a.i./kg-bw

No effects at highest 

treatment level tested

Practically 

Non-Toxic 44144406 Acceptable

Subacute Dietary 

Toxicity

Northern 

bobwhite quail

Colinus 

virginianus

LC50 >5,870

mg a.i./kg-diet

No effects at highest 

treatment level tested

Practically 

Non-Toxic 44144407 Acceptable

Avian 

Reproductive 

Toxicity

Northern 

bobwhite quail

Colinus 

virginianus

NOAEC=520 mg 

a.i./kg-diet

(Reduction in 

eggshell thickness)

N/A 44617711 Acceptable

Mammals

Acute oral 

Toxicity

Rat

Rattus 

norvegicus

LD50 >5,000 mg 

a.i./kg-bw

Practically 

Non-Toxic, 

Acute 

Toxicity 

Category 4

44144415 Acceptable

Two-Generation 

Toxicity

Rat

Rattus 

norvegicus

NOAEC =20,000 

ppm diet

LOAEC >20,000 

ppm diet

N/A 44617727 Acceptable

Terrestrial 

Invertebrates

Acute Contact 

Toxicity (adults)

Honey bee

Apis mellifera

LD50 >100 μg

a.i./bee

Practically 

Non-Toxic 44144429 Acceptable

Acute Oral 

Toxicity (adults)

72-hour LC50 >100 

μg a.i./bee

Practically 

Non-Toxic 44617717 Supplemental

(non-guideline)

Acute Larval 

Toxicity (7-day) 

72-hour LD50=3.69

μg a.i./bee 

Moderately 

Toxic 49672801 Supplemental 

(non-guideline)
34

Taxonomic 

Group Study Type Test Species Toxicity Value

Acute 

Toxicity 

Classification

Source 

(MRID) Study Classification

Chronic Larval 

Toxicity (21-day)

NOAEL=101 mg 

a.i./L N/A 45065501 Supplemental

1 Birds represent surrogates for terrestrial-phase amphibians and reptiles.

3.3.3 Ecological Incidents

The ecological incident information system (EIIS) is a database maintained by the Office of 

Pesticide Programs; the database contains 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 pesticides known or suspected of contributing to the 

incident, and results of any chemical residue analysis or other analyses conducted during incident 

investigation. EIIS incidents are categorized according to the certainty that the incident resulted 

from pesticide exposure. The Avian Incident Monitoring System (AIMS)22 is a database 

administered by the American Bird Conservancy that contains publicly available data on reported 

avian incidents involving pesticides. Many of the incidents listed in this database are also in the 

EIIS. 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.

EIIS contains six incident reports for methoxyfenozide. All six are reported bee kills in which 

methoxyfenozide was mentioned. Five reported incidents took place in California, and one in New 

York State. The legality of the uses that led to these reports is not known, nor is it known whether 

misuse of methoxyfenozide was a factor in these reported incidents. Importantly, for all of these 

incidents, more than one pesticide was named along with methoxyfenozide, meaning that the 

applicators likely tank-mixed methoxyfenozide with other chemicals and applied the mix as a 

spray. Since methoxyfenozide alone does not appear to be toxic to adult honey bees on an acute 

contact or oral exposure basis and since these bee kill incidents involved the loss of adult bees, it 

is uncertain whether methoxyfenozide was the cause of these losses. EPA does not have toxicity 

data nor does it conduct risk assessments for tank mixes of different chemicals or combinations of 

active ingredients. It is unknown whether methoxyfenozide’s potential toxicity to bees is enhanced 

or otherwise affected by other chemicals that may be tank mixed with it or sprayed concurrently. 

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

to methoxyfenozide. AIMS was also searched on February 20, 2015 and revealed no incidents to 

birds associated with methoxyfenozide. 

Table 15: Summary of Methoxyfenozide Incidents (March, 2015)

Chemical Name 

(Product Name) Crop

Incident 

Data System 

Number

Date Certainty Location

Affected Taxa

(Magnitude of 

Incident)

Application 

Method

 22 American Bird Conservancy. 2015. Avian Incident Monitoring System. 

http://www.abcbirds.org/abcprograms/policy/toxins/aims/aims/login.cfm
35

Methoxyfenozide 

(Intrepid® 2F)

Pistachios

I023107-019

July 2011 Unlikely Kings Co, 

California

Honey bees 

(92 colonies) Ground

Almonds

I024029-001 February 

2012 Possible Seneca Co, California

Honey bees 

(464 colonies) Unknown

Unknown

I024270-001

May 2012 Unlikely Seneca Co, 

New York

Honey bees 

(48 colonies)

Drift from seed 

planting

Almonds

I025162-001

May 2013 Unlikely Madera Co, 

California

Honey bees 

(12,000 colonies) Unknown

Almonds I026240-001 February 

2014 Possible Merced Co, 

California

Honey bees

(7,800 colonies) Airblast/Ground

Almonds I026517-001 March 2014 Possible Merced Co, 

California

Honey bees 

(2000 colonies) Unknown

4.0 Risk Characterization

4.1 Risk Estimation

This screening-level assessment of the labeled uses of methoxyfenozide relies on the deterministic 

RQ method to provide a metric of potential risks. The RQ provides a comparison of exposure 

estimates to toxicity endpoints (i.e., the estimated exposure concentrations are divided by acute 

and chronic toxicity values, respectively). The resulting unitless RQ values are compared to the 

Agency’s LOCs. The LOCs, when exceeded, are used by the Agency to indicate when the use of 

a pesticide, as directed by the label, has the potential to cause adverse effects to non-target

organisms. For endangered species, LOC exceedances require an additional in-depth evaluation 

of the potential co-occurrence of listed species and areas in which new use crops are grown to 

characterize risks. In all cases, RQs that exceed the risk to non-listed species LOCs also exceed 

the listed species LOCs (See Table 2 above).

4.1.1 Aquatic Organisms 

In the acute freshwater fish, acute estuarine/marine fish, and non-vascular aquatic plant toxicity 

studies submitted, there were no mortality or sub-lethal effects at the highest treatment levels tested 

(i.e., LC50, endpoints are ‘greater than’ values); therefore, these endpoints are not used to calculate 

risk quotient (RQ) values. However, the information in these studies was used to help characterize 

potential risk in the Risk Description section (4.2) of this assessment.

4.1.1.1 Aquatic Invertebrates

Acute and chronic risk to aquatic invertebrates were assessed by comparing exposure in surface 

water following methoxyfenozide use to the most sensitive toxicity endpoints identified in aquatic 

invertebrate studies. Acute RQs for freshwater invertebrates were calculated using the ACRestimated EC50 of 0.06 mg a.i./L (57 μg a.i./L) for the C. riparius, and chronic RQs were calculated 

using the empirical NOAEC of 0.0031 mg a.i./L (3.1 μg a.i./L) (pore water concentration) for the 

midge. Acute RQs for estuarine/marine invertebrates were calculated using the EC50 of 1.2 mg 
36

a.i./L (1200 μg a.i./L) for the Eastern oyster. Chronic RQs were calculated using the NOAEC of 

0.025 mg a.i./L (25 μg a.i./L) for the mysid.

For all of the registered uses of methoxyfenozide, RQs for freshwater invertebrates exceed the 

Agency’s acute risk levels of concern (LOCs) for listed (LOC=0.05) and non-listed (LOC=0.5) 

species. Chronic RQs also exceeded the LOC for freshwater invertebrates (LOC=1) for all of the 

registered uses. For estuarine/marine invertebrates, RQs for most of the registered use sites exceed 

the Agency’s acute risk LOCs for listed and non-listed species except for uses on grass forage and 

bushberries. However, for all registered uses, RQs exceed the chronic risk LOC for 

estuarine/marine invertebrates. Acute and chronic RQs for aquatic invertebrates are presented 

below in Table 16.

Table 16: Acute and Chronic RQ Values for Freshwater and Estuarine/Marine 

Invertebrates for the Registered Uses of Methoxyfenozide

Use Site 

(Scenario)

Exposure 

Type

EEC

(μg a.i./L)

Freshwater Invertebrate 

RQ1

Estuarine/Marine 

Invertebrate RQ2

Acute Chronic Acute Chronic

Citrus (FL Citrus) Acute 104 (peak) 1.82a,b 0.09a

Chronic 103 (21-day) 33.2c 4.12c

Cotton 

(NC Cotton)

Acute 185 (peak) 3.25 a,b 0.15a

Chronic 183 (21-day) 59.0 c 7.32c

Fruiting Vegetables

(FL Pepper)

Acute 135 (peak) 2.37 a,b 0.11a

Chronic 133 (21-day) 42.9 c 5.32c

Globe Artichokes (CA Lettuce) Acute 144 (peak) 2.53 a,b 0.12a

Chronic 143 (21-day) 46.1 c 5.72c

Grass Forage, Fodder Hay

(OR Grass Seed)

Acute 37.4 (peak) 0.66 a,b 0.03

Chronic 37.1 (21-day) 12.0 c 1.48c

Bushberries

(OR Berries)

Acute 52.7 (peak) 0.92 a,b 0.04

Chronic 52.2 (21-day) 16.8 c 2.09c

Peanuts

(NC Peanuts)

Acute 54.5 (peak) 0.96 a,b 0.05a

Chronic 54.0 (21-day) 17.4 c 2.16c

Corn

(MS Corn)

Acute 144 (peak) 2.52 a,b 0.12a

Chronic 143 (21-day) 46.1 c 5.72c

Grapes

(NY Grapes)

Acute 141 (peak) 2.47 a,b 0.12a

Chronic 140 (21-day) 45.2 c 5.6c

Tree Nuts

(CA Almonds)

Acute 101 (peak) 1.77 a,b 0.08a

Chronic 100 (21-day) 32.3 c 4.00c

1 Based on an ACR-calculated EC50 of 0.06 mg a.i./L (57 μg a.i./L) (midge, Chironomus riparus) and a NOAEC of 0.0031 mg a.i./L (3.1μg a.i./L) (midge, 

Chironomus riparus). 2 Based on an EC50 of 1.2 mg a.i./L (1200 μg a.i./L) (Eastern oyster, Crassostrea virginica) and a NOAEC of 0.025 mg a.i./L (25 μg a.i./L) (mysid, Americamysis 

bahia). a exceeds acute risk to listed species LOC (i.e., RQ≥0.05); b exceeds acute risk to non-listed species LOC (i.e, RQ≥0.5); c exceeds chronic risk LOC (RQ≥1).

4.1.1.2 Freshwater and Estuarine/Marine Fish

Acute risk to either freshwater fish (or aquatic-phase amphibians) or estuarine/marine fish from 

methoxyfenozide was not assessed since the 96-hr LC50 value exceeded the highest concentration 

tested and no mortality was observed at the highest concentration. Chronic RQs for freshwater 
37

fish were calculated using the most sensitive NOAEC of 530 μg a.i./L based on reduced survival 

for the fathead minnow, and chronic RQs for marine/estuarine fish were calculated using the most 

sensitive NOAEC of 1500 μg a.i./L based on reduced growth for the sheepshead minnow. Chronic

RQ values for freshwater and marine/estuarine fish do not exceed the chronic risk LOC (RQ≥1.0) 

for any of the assessed uses (Table 17). 

Table 17. Chronic RQ Values for Marine/Estuarine and Freshwater Fish from 

the Registered Use of Methoxyfenozide

Use Site 

(Scenario)

Exposure 

Type

EEC 

(μg a.i./L)

Freshwater 

Fish Chronic 

RQ1

Marine/Estuarine 

Fish Chronic 

RQ2

Citrus (FL Citrus) Chronic 103 (21-day) 0.19 0.69

Cotton 

(NC Cotton) Chronic 183 (21-day) 0.35 0.12

Fruiting Vegetables

(FL Pepper) Chronic 133 (21-day) 0.25 0.09

Globe Artichokes (CA Lettuce) Chronic 143 (21-day) 0.27 0.10

Grass Forage, Fodder Hay

(OR Grass Seed) Chronic 37.1 (21-day) 0.07 0.02

Bushberries

(OR Berries) Chronic 52.2 (21-day) 0.10 0.03

Peanuts

(NC Peanuts) Chronic 54.0 (21-day) 0.10 0.04

Corn

(MS Corn) Chronic 143 (21-day) 0.27 0.10

Grapes

(NY Grapes) Chronic 140 (21-day) 0.26 0.09

Tree Nuts

(CA Almonds) Chronic 100 (21-day) 0.19 0.07

1

Based on a NOAEC of 530 μg a.i./L (fathead minnow, Pimephalas promelus). 2

Based on a NOAEC of 1500 μg a.i./L (sheepshead minnow, Cyprinodon variegatus).

4.1.1.3 Aquatic Plants

As stated earlier, the freshwater green algae (P. subcapitata) was the most sensitive aquatic nonvascular plant tested, but the endpoint in the toxicity study was non-definitive, i.e., the effect 

concentration for 50% mortality of the algae exceeded the highest concentration tested (EC50>3.4 

mg a.i./L), suggesting that the chemical’s solubility (3.3 mg/L) may limit its impacts on aquatic 

non-vascular plants. As noted earlier, data on the effects of methoxyfenozide on aquatic vascular 

plants are not available. However, aquatic plant data for tebufenozide, an IGR in the same 

chemical class and mode of action, demonstrated no significant effect on vascular aquatic plant 

survival or growth in a seven-day static-renewal test with duckweed (Lemna gibba) or in a 96-

hour nonvascular aquatic plant toxicity test with green algae (P. subcapitata). Also, tebufenozide 

degradates had no effect on the green algae at concentrations up to the limits of water solubility of 

tebufenozide (0.83 mg/L). Therefore, aquatic plant RQs for methoxyfenozide were not calculated. 
38

Based on aquatic plant toxicity data for methoxyfenozide and tebufenozide, the likelihood of 

adverse effects on aquatic plants from exposure to methoxyfenozide is considered low.

4.1.2 Terrestrial Organisms

4.1.2.1 Risk to Birds 

In the avian acute toxicity studies submitted, there were no mortality or sub-lethal effects at the 

highest treatment levels tested (i.e., the acute oral LD50 and sub-acute dietary LC50 values are 

‘greater than (>)’ values); therefore, acute RQs for birds (and for terrestrial-phase amphibians and 

reptiles for which birds serve as surrogates) were not calculated. However, the information in these 

studies was used to help characterize risk in the ‘Risk Description’ section of this assessment. 

Exposure estimates for birds were calculated using upper-bound Kenaga values calculated using 

T-Rex version 1.5.2. For chronic risk to birds, the highest (most conservative) exposure estimates 

(EECs) generated by T-REX were dietary-based EECs (See Section 3.2.3.1). Ingestion of 

contaminated prey was estimated using KABAM based on BCF values, and 1-in-10 year 60-day 

water-column concentrations were estimated using the SWCC. Dietary-based EECs were 

compared to the most sensitive chronic toxicity endpoints to calculate chronic RQs. The highest 

dietary-based EECs for the registered uses resulted from uses on corn, tree nuts and cotton (see 

Table 10). These three uses were chosen to represent the most conservative estimates of chronic 

risk to birds from all of the registered uses of methoxyfenozide. Chronic RQs for use on corn, tree 

nuts and cotton are presented below in Table 18. Based on the example of these most conservative 

estimates, we conclude that chronic avian risks for all use patterns are below the Agency’s level 

of concern.

Table 18. Dietary-based Upper-Bound Avian Chronic EEC and RQ Values for 

Methoxyfenozide 

Application 

Method

Dietary-Based EECs and RQs1

Short Grass Tall Grass Broadleaf Plants/

Small Insects

Fruits/Pods/

Seeds/

Large Insects

EEC2 RQ EEC RQ EEC RQ EEC RQ

Use Site/Crop Group (Max. Single Application Rate)

Corn (0.25 lb a.i./A)

Ground/Aerial 220 0.42 101 0.19 124 0.24 13.8 0.03

Tree Nuts (0.38 lb a.i./A)

Ground/Aerial 278 0.53 127 0.24 156 0.30 17.4 0.03

Cotton (0.4 lb a.i./acre)

Ground/Aerial 292 0.56 134 0.26 164 0.32 18.3 0.04 1 Based on a NOAEC of 520 mg a.i./kg-diet (Northern bobwhite quail, Colinus virginianus). 2 From T-REX, Version 1.5.2. See Appendix D for an example T-REX printout.
39

4.1.2.2 Risk to Mammals

In the available mammalian acute toxicity studies, there were no mortality or sublethal effects 

observed at the highest treatment levels tested (i.e., the acute oral LD50 is a ‘greater than (>)’ value); 

therefore, acute RQs were not calculated for mammals. However, information from these studies 

was used to characterize risk in the Risk Description section of this assessment.

In mammals, chronic exposure to rats resulted in no treatment-related effects on reproductive 

parameters for adult (parent) animals, nor were effects on growth or survival noted. For ecological 

risk assessment purposes, the chronic NOAEL from this study is 20,000 ppm. 

Exposure estimates for mammals were calculated using upper-bound Kenaga values calculated 

using T-Rex version 1.5.2. For chronic risk to mammals, the highest (most conservative) exposure 

estimates (EECs) generated by T-REX were dietary-based EECs (See Section 3.2.3.1). Ingestion 

of contaminated prey was estimated using KABAM based on BCF values, and 1-in-10 year 60-

day water-column concentrations were estimated using the SWCC. As a conservative measure, 

dietary-based EECs were compared to the most sensitive chronic toxicity endpoints to calculate 

chronic RQs. The highest dietary-based EECs resulted from uses on corn, tree nuts and cotton (see 

Table 10). These three uses were chosen to represent the most conservative estimates of chronic 

risk to mammals from all of the registered uses of methoxyfenozide. Chronic mammalian RQs 

are presented below in Table 19. Based on the example of these most conservative estimates, we 

conclude that chronic mammalian risks for all use patterns are below the Agency’s level of 

concern.

Table 19. Dietary-based Upper-Bound Mammalian Chronic EEC and RQ Values for 

Methoxyfenozide

Application 

Method

Dietary-Based EECs and RQs1

Short Grass Tall Grass Broadleaf Plants/

Small Insects

Fruits/Pods/

Seeds/

Large Insects

EEC2 RQ EEC RQ EEC RQ EEC RQ

Use Site/Crop Group (Max. Single Application Rate)

Corn (0.25 lb a.i./A)

Ground/Aerial 220.02 <0.01 100.84 <0.01 123.76 <0.01 13.75 <0.01

Tree Nuts (0.38 lb a.i./A)

Ground/Aerial 277.73 <0.01 127.29 <0.01 156.23 <0.01 17.36 <0.01

Cotton (0.4 lb a.i./acre)

Ground/Aerial 292.35 <0.01 133.99 <0.01 164.45 <0.01 18.27 <0.01 1 Based on a NOAEL of 20,000 mg a.i./kg-diet (rat). 2 From T-REX, Version 1.5.2. See Appendix D for an example T-REX printout.

Insufficient data are available to calculate a reliable metabolism rate constant to parameterize 

KABAM; therefore, the empirical BCF values for fish were used to estimate methoxyfenozide 

concentrations in aquatic organisms. The empirical BCF value for methoxyfenozide is 263 L/kg 
40

in whole fish and was measured for the bluegill sunfish. Maximum 1-in-10-year 60-day average 

EECs for the scenarios explored for aquatic modeling ranged from 12.9 to 182 μg a.i./L. The 

estimated concentrations in aquatic organisms resulting from this range of EECs are used with the 

BCFs to bracket the potential concentrations of methoxyfenozide in aquatic vertebrate tissues (at 

steady state) in areas vulnerable to runoff. It should be noted that tissue concentrations in aquatic 

vertebrates will likely be limited by the toxicity of methoxyfenozide on these organisms. For 

instance, the NOAEC for aquatic vertebrates exposed to methoxyfenozide is 3.1 μg a.i./L. At this 

concentration, delayed emergence and development were observed. Given that we expect a range 

of sensitivity in different aquatic invertebrates, some sensitive aquatic vertebrates would be 

expected to have effects at the estimated concentrations while less sensitive species could carry 

residues in tissue without showing effects. Assuming EECs of 12.9 to 182 μg a.i./L and a BCF 

value of 263 L/kg for whole fish, methoxyfenozide concentrations in aquatic vertebrate tissues 

may range from 3.3 to 48 mg a.i./kg (diet; BCF x EEC = concentration in fish). The highest of 

these concentrations is lower than the chronic dietary endpoints for mammals and birds. The 

chronic RQ for birds is 0.09 and for mammals is <0.01 indicating that exposure for birds and 

mammals consuming fish contaminated with methoxyfenozide is not likely to result in a risk 

concern (Table 20).

Table 20. RQ Values for Birds and Mammals Consuming Fish

Use 

Scenario

Water-Column 

60-day average EEC 

(μg/L)

BCF 

(L/kg)

Methoxyfenozide 

concentration in 

fish (mg/kg)

Chronic RQ

Birds

NOAEC=

520 mg/kg-diet

Mammals

NOAEC=

20,000 mg/kg-diet

Cotton1 178 236 46.8 0.09 <0.01

1NC cotton; 0.45 x 2 (applications) + 0.22 x 1 application. @ 10-d interval

4.1.2.2 Terrestrial Plants

As noted earlier, no data are available to assess the effects of methoxyfenozide on terrestrial plants. 

However, terrestrial plant toxicity data (tier 1 vegetative vigor and seedling emergence studies) 

are available for tebufenozide, an insect growth regulator in the same class as methoxyfenozide. 

By making the conservative assumption that the non-definitive values (i.e., EC25>1.94 lbs a.i./A

and NOAEC<0.98 lbs a.i./A) from the seedling emergence and vegetative vigor studies for 

tebufenozide are definitive (i.e., assuming EC25=1.94 lb a.i./acre) and assuming a single 

application at the maximum label rate for the cotton use site (the highest single application rate) 

resulted in RQs that are below the LOC for risk to terrestrial plants (LOC=1.0). 

4.1.2.3. Terrestrial Invertebrates

As noted previously, methoxyfenozide is classified as ‘practically non-toxic’ to adult honey bees

both on an acute oral and contact exposure basis but has been shown to be toxic to target 

lepidopteran pest species such as the European corn borer (a common pest of corn) on an acute 

dietary exposure basis (Trisyono and Chippendale, 1997). Lepidopterans include more than 

11,200 species in North America including the monarch butterfly (Danaus plexippus) for which 
41

certain subpopulations are in decline,

23 and the listed Karner blue butterfly (Lycaeides melissa 

samuelis)24. There is uncertainty surrounding the extent of exposure of non-target, beneficial 

lepidopterans to methoxyfenozide (e.g., timing of applications relative to presence of the 

lepidopterans, and location of applications relative to habitat or areas where lepidopterans feed.

In 2006, EFED completed an interim endangered species risk assessment for the Karner Blue 

Butterfly (Lycaeides melissa samuelis) for the use of methoxyfenozide on cranberries in 

Wisconsin25. An endangered species protection bulletin has been developed for the use of 

methoxyfenozide in areas where use of methoxyfenozide may overlap with habitat of the Karner 

Blue Butterfly (See: http://www.epa.gov/oppfead1/endanger/bulletins.htm).

As stated earlier in this assessment, adult honey bees do not appear to be sensitive to 

methoxyfenozide on an acute oral or contact exposure basis. Therefore, RQs for adult honey bees 

were not calculated. 

Screening-level RQ values were estimated for larval honey bees using the results of the recently 

submitted acute toxicity data (MRID 49672801) and EECs for pollen and nectar based on 

conservative models discussed in the Guidance for Assessing Pesticide Risks to Bees (US EPA, 

2014). The food consumption rate of 0.124 g/day for 5-day old larval honey bees was taken from 

the Guidance; 5-day old larvae consume the more food than larvae of any other age. Based on the 

7-day larval toxicity data (LD50=3.69 μg/bee), the screening-level RQs for larval honey bees range 

from 0.03 to 1.4 (Table 21) for the maximum application rate for almonds as well as typical

application rate. At the maximum application rate, the RQ (1.4) exceeds the acute risk LOC of 

0.04. RQ values were further refined using measured residue values discussed in Section 3.2.3.2,

and the resulting RQ is 0.32, which is below the acute risk LOC.

Table 21. Larval Honey Bee Exposure (EECs) and RQ Values for Almonds Treated with 

Methoxyfenozide

Application 

Method (Rate)

(lb a.i./Acre)

Pollen EEC

(mg a.i./kg 

pollen)

Nectar 

EEC

(mg a.i./kg 

nectar)

Larvae 

Consumption 

Rate (g/day)5

LD50

(μg a.i./bee)3 Pollen RQ4 Nectar RQ4

RQs using Default Exposure Estimates1

Ground 

(0.19 lb 

a.i./Acre)

20.91 N/A 0.124 3.69 0.70 N/A

Ground 

(0.38 lb 

a.i./Acre)

41.81 N/A 0.124 3.69 1.40 N/A

RQs using Refined Exposure Estimates

 23 From US FWS (http://www.fws.gov/savethemonarch/): North American monarch butterflies are in trouble. Threats, including loss of 

milkweed habitat needed to lay their eggs and for their caterpillars to eat, are having a devastating impact on their populations and the 

migration phenomenon.

24 North Carolina State University Entomology Resource Library website. Accessed 7/9/15. Available at: 

http://www.cals.ncsu.edu/course/ent425/library/compendium/lepidoptera.html 25 US EPA, 2006.
42

Ground 

(0.19 lb 

a.i./Acre)

9.422 0.7946 0.124 3.69 0.32 0.03

1. Default EECs calculated using Guidance for Assessing Pesticide Risk to Bees (US EPA, 2014) (=AR lb a.i./A*110 μg a.i./day).

2. Peak corbicular pollen residue value measured in the almond residue study with methoxyfenozide (MRID 48962202)

3. LD50 from the acute (7-day) larval honey bee toxicity study (MRID 49672801).

4. RQ = [EEC (ppm)*Consumption rate (g/day)/LD50 (μg a.i./bee)].

5. Consumption rates from Guidance for Assessing Pesticide Risk to Bees (US EPA, 2014).

6. Peak nectar residue value collected from honey bees’ stomachs measured in the almond residue study with methoxyfenozide (MRID 

48962202).

4.2. Risk Description

Methoxyfenozide is characterized as persistent and moderately mobile and is expected to move 

into surface water through runoff and spray drift following application. The widespread and 

prevalent use of methoxyfenozide; its physio-chemical characteristics and eco-toxicity profile; and 

evidence of residues of the chemical in various environmental matrices (e.g., soil, pollen) suggest

that non-target lepidopterans and aquatic invertebrates can be exposed to the insecticide. The 

results of this screening-level risk assessment indicate that the registered uses of methoxyfenozide 

have the potential for direct adverse effects on listed and non-listed freshwater invertebrates. The 

RQs for freshwater invertebrates exceed the Agency’s LOCs for acute risk to listed and non-listed 

species and LOCs for chronic risks to listed and non-listed species for all of the registered uses of 

methoxyfenozide. RQ values for estuarine/marine invertebrates exceed the acute risk to listed 

species LOC for all but two of the uses evaluated and exceed the chronic risk LOC for all of the 

uses evaluated. The RQs for terrestrial invertebrates also exceed the Agency’s LOCs for acute 

risk (0.4) for the registered use on almonds. These results are based on EECs derived for maximum 

labeled rates for spray applications of methoxyfenozide. 

The likelihood of direct adverse effects to birds (terrestrial-phase amphibians and reptiles), 

mammals, fish (aquatic-phase amphibians), terrestrial and aquatic plants, and estuarine/marine 

invertebrates from exposure to methoxyfenozide as a result of the registered uses is expected to be 

low. However, the extent to which other taxa that may depend on freshwater aquatic invertebrate 

species may be indirectly affected is uncertain.

4.2.1 Risk to Aquatic Organisms

Methoxyfenozide is characterized as moderately toxic to freshwater fish, estuarine/marine 

invertebrates, and estuarine/marine fish, and highly toxic to freshwater invertebrates on an acute 

exposure basis. Acute toxicity risk estimates were non-definitive (i.e., the EC50 or LC50 values 

exceeded the highest concentration tested) for freshwater and estuarine/marine fish and aquatic 

nonvascular plants, suggesting that the toxicity of the compound to these taxa may be limited by 

its solubility (3.3 mg/L).

Aquatic exposure estimates are based on EECs obtained using the SWCC. These EECs are 

typically regarded as representing conservative estimates of exposure because the input value for 

the application rate is the labeled maximum, the entire watershed is assumed to be cropped and 

treated, the weather pattern producing the highest concentrations with a 10-year return frequency
43

is used, and the geographic location of use is regarded as representative of high-end potential for 

pesticide runoff. Methoxyfenozide has been registered for use in the U.S. for 15 years on a broad 

range of use sites. Given that methoxyfenozide is persistent and mobile and that the use pattern 

involves frequent, repeated applications throughout the growing season, the assumptions built into 

the SWCC may not be considered conservative for all use sites.

In TFD studies performed on sand (WA and GA), loamy sand (CA), and loam (TX) soils, 

methoxyfenozide applied to fields dissipated with DT50s (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 studies, at concentrations up to 0.039 mg/kg soil (39 μg/kg soil), providing evidence of 

leaching. In the surface water monitoring study in lotic and lentic water bodies (MRID 49340301), 

peak levels of methoxyfenozide ranged from 0.845 μg/L (lentic) to 1.31 μg/L (lotic). Compared 

to the EECs for methoxyfenozide in surface water, these values are more than 100X lower than 

peak EECs estimated with EFED’s models (see Table 7). 

For all of the registered uses of methoxyfenozide, RQs for freshwater invertebrates exceed the 

Agency’s levels of concern (LOCs) for acute risk to listed (LOC=0.05) and non-listed (LOC=0.5) 

species. RQs also exceed the chronic risk LOC for freshwater invertebrates (LOC=1) for all of the 

registered uses (Table 3). Except for the use of methoxyfenozide on grass forage and bushberries, 

RQs exceed the Agency’s acute risk LOCs for listed and non-listed species of estuarine/marine 

invertebrates. Finally, for all registered uses, chronic risk RQs for estuarine/marine invertebrates 

exceed the Agency’s LOCs.

Uncertainties

Acute RQs for freshwater invertebrates (Table 13) may underestimate risks since the EC50 for the 

more sensitive midge was approximated using an ACR for the freshwater invertebrate D. magna 

rather than an experimentally derived EC50. Additionally, it is important to note that if RQs for 

freshwater invertebrates are calculated using the D. magna EC50 of 3.7 mg a.i./L and the NOAEC 

of 0.20 mg a.i./L instead of using the ACR representing the midge, LOCs are not exceeded (acute 

RQ=0.05/cotton, chronic RQ=0.9), indicating that the likelihood of adverse effect to similarly 

sensitive aquatic invertebrates from the registered uses of methoxyfenozide is low. For acute and 

chronic exposures of marine/estuarine and freshwater aquatic invertebrates, risks would be lower 

than levels of concern if monitoring data were used in place of EECs. Alternatively, risks could 

be underestimated since monitoring data may not represent peak concentrations. 

Because there were no mortalities or sub-lethal effects at the highest treatment levels tested in the 

freshwater fish and estuarine/marine fish acute toxicity studies, RQ values for acute exposures are 

not included in the Risk Estimation section of this assessment. However, estimates of acute risk 

for fish can have value in characterizing risk overall. RQs shown here are based on the conservative 

assumption that the highest concentrations tested in the acute toxicity studies represent endpoints 

(i.e., LC50 = 4.2 mg a.i./L for freshwater fish and LC50 = 2.8 mg a.i./L for estuarine/marine fish). 

A similar assumption can be made for aquatic plants (EC50 = 3.4 mg a.i./L for freshwater algae).

As stated earlier, in some cases the non-definitive acute toxicity endpoint suggests that the 

potential acute toxicity of methoxyfenozide may be limited by the chemical’s solubility (3.3 mg/L 

at 25oC). Using the peak aquatic EEC for aerial application to cotton (0.185 mg a.i./L), all of these
44

acute RQs (freshwater fish RQ = 0.04; estuarine/marine fish RQ = 0.06; freshwater algae RQ = 

0.05) would be below the Agency's acute risk LOCs. The actual risks would be lower because no 

effects were observed at the highest treatment levels tested. This analysis is consistent with the 

absence of aquatic incidents for methoxyfenozide in EPA’s incident reporting databases and our 

findings for chronic risks to freshwater and estuarine/marine fish, i.e., the RQs do not exceed the 

Agency’s LOCs for listed or non-listed species. 

No data are available to assess the potential risks of methoxyfenozide exposure to aquatic vascular 

plants; however, as discussed earlier in Section 4.1.1.3, given that aquatic vascular plant data for 

tebufenozide did not result in definitive toxicity, the mode of action of methoxyfenozide as an 

insect growth regulator and that toxicity data for nonvascular aquatic plants did not demonstrate 

adverse effects up to the solubility limit (3.3 mg/L) of the compound, the current information does 

not suggest that there would be adverse effects on plants from exposure to methoxyfenozide. 

Finally, there are no reported plant incidents in EFED’s incident databases.

Therefore, the likelihood of direct adverse effects to fish and aquatic-phase amphibians as well as 

aquatic plants from exposure to methoxyfenozide as a result of the registered uses is expected to 

be low. However, the extent to which fish and aquatic-phase amphibians are indirectly affected by 

direct effects on aquatic invertebrates is uncertain.

4.2.2 Risks to Terrestrial Vertebrates and Plants

On an acute exposure basis, methoxyfenozide is classified as practically non-toxic to birds, 

mammals and adult honey bees. 

Because no mortality or sub-lethal effects were observed at the highest treatment levels tested in 

the avian acute oral and sub-acute dietary studies, standard RQ values are not included in the Risk 

Estimation section of this assessment. In order to gain a better understanding of how the EECs for 

the maximum methoxyfenozide application rates relate to the toxicity data currently available for 

birds, the T-REX model was used to calculate RQs, shown here, using the conservative assumption 

that the highest values tested in the avian acute toxicity studies represent endpoints (i.e., acute oral 

LD50 = 2,250 mg/kg-bw and sub-acute dietary LC50 = 5,870 mg/kg diet for bobwhite quail). In this 

analysis, none of the RQs exceeds the Agency’s acute risk LOC for listed (LOC=0.1) or non-listed 

species (LOC = 0.5). The actual risks would be lower because no effects were observed at the 

highest treatment levels tested. As discussed previously in the Risk Estimation section, for chronic 

risk, RQs for birds in several forage categories are all below the Agency’s chronic risk LOC.

Therefore, the potential for adverse effects to birds (terrestrial-phase amphibians and reptiles) from 

acute, sub-acute, or chronic exposure to methoxyfenozide from the registered uses is considered 

low. The extent to which birds, terrestrial-phase amphibians and reptiles that depend on freshwater 

aquatic invertebrate species may be indirectly affected is uncertain.

Similarly for mammals, because there was no mortality or sub-lethal effects at the highest 

treatment levels tested in the acute oral toxicity study with rats, the standard acute RQ values are 

not included in the Risk Estimation section of this assessment. Using the conservative assumption 

that the highest value tested in the acute toxicity study represents the endpoint (i.e., acute oral LD50
45

=5,000 mg/kg-bw), acute RQs <0.01 for all of the assessed registered uses and do not exceed the 

Agency’s acute risk LOCs for mammals. The actual risks would be lower since no acute mortality 

effects were observed at the highest treatment levels tested. This analysis is consistent with our 

findings on chronic risks to mammals, i.e., exposure to rats did not result in adverse effects up to 

the 20,000 ppm dose level (LOAEC>20,000 ppm, highest dose tested) in a 2-generation 

reproductive toxicity study. The NOAEC from this study is 20,000 ppm (or mg a.i./kg-diet).

In the Risk Estimation section of this assessment, chronic risk to mammals was estimated by 

comparing the NOAEC (20,000 mg a.i./kg-diet) to upper-bound exposure values from T-REX. As

shown in Table 19, RQs for all of the uses are below than 0.01, and thus, do not exceed the chronic 

risk LOC (1.0). See Appendix C for details.

Therefore, the likelihood of direct adverse effects to mammals from acute and chronic exposures

to methoxyfenozide from registered uses is considered low. 

No data are available to assess the potential risks of methoxyfenozide exposure to terrestrial plants; 

however, as discussed in Section 3.3.2, terrestrial plant data for the IGR tebufenozide can be used 

to inform the potential toxicity of methoxyfenozide to terrestrial plants and indicate that the 

likelihood of adverse effects to plants from exposure to methoxyfenozide is considered low (see 

Section 2.0). Also, there are no reports in EFED’s incident data bases of plant damage resulting 

from exposure to methoxyfenozide.

4.2.3 Risks to Terrestrial Invertebrates

Methoxyfenozide is registered on a number of bee-attractive crops26 including almonds (tree nuts), 

cotton, berries, citrus, fruiting vegetables, and can be applied to these crops during bloom, when 

bees are actively foraging. Based on the current use patterns for this chemical, it is likely that nontarget terrestrial invertebrates are exposed to methoxyfenozide. The residue study in honey bee 

colonies discussed in Section 3.2.3.2 provides evidence of methoxyfenozide exposure to honey

bees in matrices relevant to honey bees (i.e., pollen and nectar), even at an application rate that is 

half the maximum rate listed on labels (0.19 lb a.i./Acre). 

Risks for larval honey bees were initially calculated using the more conservative model-generated

values for exposure and were further refined based on empirical exposure data from the residue 

study in almonds. Using the maximum application rate and the model-generated EEC, the RQ (1.4) 

exceeds the acute risk LOC; however, refined exposure estimates from the residue study in 

almonds and using a lower application rate results in RQs that do not exceed the acute risk LOC

for bee larvae.

As discussed earlier, methoxyfenozide does not appear to be acutely toxic to adult honey bees, and 

the submitted toxicity data for honey bee colonies indicate that the compound does not adversely 

affect colony brood development and/or overwintering survival, although some confounding 

effects were noted in the field-based studies with whole colonies. The semi-field honey bee brood 

 26 Attractiveness of Agricultural Crops to Pollinating Bees for the Collection of Nectar and/or Pollen. Available at: 

http://www.ree.usda.gov/ree/news/Attractiveness_of_Agriculture_crops_to_pollinating_bees_Report-FINAL.pdf
46

study involved feeding bees sucrose containing 101 mg methoxyfenozide/L sucrose syrup while 

the longer-term colony overwintering study fed bees different concentrations of methoxyfenozide, 

ranging from 6.25-100 mg methoxyfenozide/L sucrose syrup. These test concentrations were fed 

to adult bees and do not ensure that larval honey bees were exposed to the test substance; however, 

this uncertainty would apply to methoxyfenozide residues resulting from actual use as well. 

The treatment levels used in the two field studies are substantially higher than those used in the

laboratory-based acute larval toxicity study in which the LD50 was determined to be 3.69 μg 

a.i./larva. Although the screening-level assessment, based on maximum label application rate, 

shows risks that exceed the acute risk LOC for honey bee larvae, the field based studies do not 

indicate an adverse effect to brood development and/or colony overwintering success. 

Refinements using measured residues in pollen/nectar reduced RQ values below the acute risk 

LOC; however, these refinements were based on residue levels when methoxyfenozide was 

applied at half the maximum application rate. There is uncertainty regarding the extent to which 

the treatment concentrations in sucrose solutions used to treat the test colonies are representative 

of those resulting from the use of methoxyfenozide at the maximum application rate. 

It is unclear why effects were manifested in the laboratory study but not in semi-field, colony-level 

studies. In a real-world setting, as colony-level studies are designed to reflect, the larval diet during 

early stages of development consists largely of royal jelly, a secretion produced by the 

hypopharyngeal glands of nurse bees. It is possible that the concentration of methoxyfenozide in 

the royal jelly produced in the hive, where adult bees were feed sucrose syrup containing 

methoxyfenozide, was lower in concentration than what was fed directly to the larvae in the 

laboratory-based study. Also, the laboratory-based study involved a single exposure to 

methoxyfenozide while the duration of exposure in the colony-level studies was longer. There 

were confounding issues in both types of studies. Additional laboratory-based toxicity data would 

be useful to resolve whether the toxicity expressed after a single dose is reflected in a longer-term 

study. The 21-day larval toxicity test developed by the Organization for Economic Cooperation 

and Development would provide a means of addressing this uncertainty as it is a repeat dose study 

that extends through adult emergence.

Methoxyfenozide has been associated with six bee kill incident reports to EPA since 2011. 

Although methoxyfenozide was identified in these reports, other pesticides were also in use at the 

time of these incidents. While there is uncertainty regarding the potential effects of complex tank 

mixtures involving methoxyfenozide in use by growers, the available laboratory and field data do 

not indicate a linkage between the losses reported in bee kill incidents and methoxyfenozide as 

effects were typically associated with adult bee mortality and the laboratory/field studies indicate 

that methoxyfenozide is practically non-toxic to adult bees.

While lepidopteran pests are the target for methoxyfenozide use, lepidopterans also include nontarget valued and beneficial moths and butterflies, including unlisted species (e.g., the monarch 

butterfly) and listed species (e.g., Karner blue butterfly). There is uncertainty surrounding the 

extent of exposure of non-target lepidopterans to methoxyfenozide. Applications in areas that 

overlap with habitat or feeding areas for these lepidopterans are potential threats, depending on the 

time of year and other factors. 
47

4.3. Conclusions

 

While methoxyfenozide is expected to persist in the environment and move to surface water via 

runoff/erosion, data on both fish and invertebrates indicate that the compound does not 

bioconcentrate and it depurates relatively quickly once organisms are no longer exposed. A 

monitoring study conducted using lentic (static) and lotic (flowing) water bodies in California, 

Mississippi, and Michigan showed no apparent accumulation of methoxyfenozide in benthic 

sediments and the water columns of surface water at any monitoring sites. The frequency of 

sampling in the study was less than the use intensity and duration reflected in modeling, therefore 

the EECs values may be conservative. Available data indicate that for both freshwater and 

estuarine/marine fish, the toxicity of methoxyfenozide appears limited by its solubility in water 

where no adverse effects (i.e., mortality or sublethal effects) were observed on fish following acute 

exposure to the compound up to its solubility limit. 

For aquatic organisms, the screening-level assessment concludes that most of the registered uses 

of methoxyfenozide result in potential acute risks of concern for listed and non-listed freshwater 

invertebrates and listed estuarine/marine invertebrates. Additionally, most registered uses result 

in potential chronic risks to freshwater and marine/estuarine invertebrates.

For terrestrial organisms, no acute or chronic risks of concern are identified for birds, terrestrialphase amphibians, reptiles or mammals. There are data to indicate that lepidopteran species of 

terrestrial invertebrates are sensitive to methoxyfenozide. Although available acute toxicity data 

do not indicate potential risk to adult honey bees, it now appears that larval honey bees may be 

sensitive to methoxyfenozide under the laboratory conditions tested. Acute toxicity data for larval 

honey bees combined with exposure calculated using default (conservative) assumptions, Tier 1 

risk estimates exceed the acute risk LOCs for larval honey bees; however, when risk estimates 

were refined using measured concentration, the RQ no longer exceeds the acute risk LOC. 

Laboratory-based chronic toxicity data for larval honey bees would increase the confidence in risk 

conclusions and address uncertainties about the potential risk to terrestrial invertebrates and lead 

to more robust risk conclusions. Specifically, a 21-day larval toxicity study of methoxyfenozide

which extends through adult emergence would help to address uncertainties. 

Finally, the likelihood of adverse effects to plants from exposure to methoxyfenozide is considered 

to be low.

4.4. Endocrine Disruptor Screening Program

As required by FIFRA and the Federal Food, Drug, and Cosmetic Act (FFDCA), EPA reviews 

numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, 

these studies include acute, subchronic and chronic toxicity, including assessments of 

carcinogenicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity. 

These studies include endpoints which may be susceptible to endocrine influence, including effects 

on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, 

fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard 

assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and 
48

reproductive effects in different taxonomic groups. As part of this preliminary risk assessment, 

EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment 

scenarios from the existing hazard database. However, as required by FFDCA section 408(p), 

methoxyfenozide is subject to the endocrine screening part of the Endocrine Disruptor Screening 

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 substance 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 interact 

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 available 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 FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 

2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals, 

which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of chemicals 

identified for EDSP screening was published on June 14, 2013[1] and includes some pesticides 

scheduled for registration review and chemicals found in water. Neither of these lists should be 

construed as a list of known or likely endocrine disruptors. Methoxyfenozide is not on List 1. For 

further information on the status of the EDSP, the policies and procedures, the lists of chemicals, 

future lists, the test guidelines and Tier 1 screening battery, please visit EPA’s EDSP website[2].

4.5. Federally Threatened and Endangered (Listed) Species of Concern

Consistent with the Agency’s responsibility under the Endangered Species Act (ESA), the Agency 

will evaluate risks to listed species from registered uses of pesticides during Registration Review. 

The process for evaluating potential risks to listed species is further described at 

http://www.epa.gov/oppfead1/endanger/litstatus/riskasses.htm.

In 2006, EFED completed an interim endangered species risk assessment for the Karner Blue 

Butterfly (Lycaeides melissa samuelis) for the use of methoxyfenozide on cranberries in 

Wisconsin27. Endangered species protection bulletins for the use of methoxyfenozide in areas 

where use of methoxyfenozide may overlap with habitat of the Karner Blue Butterfly are posted 

to the Agency’s website (See: http://www.epa.gov/oppfead1/endanger/bulletins.htm and

http://54.84.207.203/BLT_Public/.)

 [1] See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of 

chemicals.

[2] Available: http://www.epa.gov/endo/

27 US EPA, 2006.
49

5. References

FAO, 2000. Food and Agriculture Organization of the United Nations. Pesticide Disposal Series 

8. Assessing Soil Contamination: A Reference Manual. Appendix 2. Parameters of pesticides 

that influence processes in the soil. Editorial Group, FAO Information Division: Rome, 2000. 

http://www.fao.org/docrep/003/X2570E/X2570E00.htm. 

Fletcher, J.S., J.E. Nellesson and T. G. Pfleeger. 1994. Literature review and evaluation of the 

EPA food-chain (Kenaga) nomogram, an instrument for estimating pesticide residues on plants. 

Environ. Tox. And Chem. 13(9):1383-1391. 

Goring, C.A. I.; Laskowki; D.A., Hamaker, J.H.; and Meikle, R.W. 1975. Principles of pesticide 

degradation in soil. pp. 135-172 in (Haque, R. and Freed, V.H. eds.) Environmental dynamics of 

pesticides. Plenum Press, NY.

Hoerger, F. and E.E. Kenaga. 1972. Pesticide residues on plants: correlation of representative 

data as a basis for estimation of their magnitude in the environment. IN: F. Coulston and F. 

Corte, eds., Environmental Quality and Safety: Chemistry, Toxicology and Technology. Vol 1. 

Georg Theime Publishers, Stuttgart, Germany. Pp. 9-28.

Intrepid® 2F Master Label, 2013. Registration Number 62719-442. Amended 04-19-13. Provided 

by Registration Division, Office of Pesticide Programs, US EPA. F3B / Intrepid 2F / MSTR 

Amend / 04-19-13. file: Intrepid 2F-442 MSTR 12Jul12f.doc

LaLone, C. A., Villeneuve, D. L., Garber, K., Tollefsen, K.E., Ankley, G. T. 2014. Conservation 

of Lepidopteran Ecdysteroid Receptor Provides Evidence for Butterfly Susceptibility to 

Diacylhydrazine and Bisacylhydrazine Chemicals. Society of Environmental Toxicology and 

Chemistry 35th Annual Meeting, 11/11/2014. Vancouver, Canada. 

Mommaerts, V. et. al. 2006. Bumblebees can be used in combination with juvenile hormone

analogues and ecdysone agonists; Ecotoxicology (2006) 15:513–521.

Shimizu, B., Y. Nakagawa, K. Hattori, K. Nishimura, N. Kurihara, and T. Ueno, 1997. Molting 

hormonal and larvicidal activities of aliphatic 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).

US EPA, 2004. Overview of the Ecological Risk Assessment Process in the Office of Pesticide 

Programs. U.S. Environmental Protection Agency, Endangered and Threatened Species Effects 

Determinations, Office of Prevention, Pesticides and Toxic Substances Office of Pesticide

Programs, Washington, D.C. 100 pgs. January 23.
50

US EPA, 2006. Interim Risk Assessment for the Karner Blue Butterfly for the Use of 

Methoxyfenozide on Cranberries in Wisconsin. U.S. Environmental Protection Agency, Office 

Fate and Effects Division, October 19, 2006. 

US EPA. 2009. Guidance for Selecting Input Parameters in Modeling the Environmental Fate 

and Transport of Pesticides. U.S. Environmental Protection Agency, Office Fate 

and Effects Division, Oct. 22, 2009. Online at: 

http://www.epa.gov/oppefed1/models/water/input_parameter_guidance.htm

US EPA, 2011. Review of Addendum to Site Selection Report with Recommended Alternate 

Sampling Sites for Lentic Water Bodies in California (MRID 47809904) (MRID: 478099-04). 

From C. Peck (EFED) and M. Echeverria (EFED) to C. Myers (RD) and R. Gebken (PRD). DP 

barcode 394308. October 12, 2011.

US EPA, 2012a. Screening Level Usage Analysis for Methoxyfenozide. Biological and 

Economic Analysis Division, Office of Pesticide Programs, US EPA; Date: June 19, 2012.

US EPA. 2012. Guidance for Selecting Input Parameters for Modeling Pesticide Concentrations 

in Groundwater Using the Pesticide Root Zone Model. Office of Chemical Safety and Pollution 

Prevention, Office of Pesticide Programs, Environmental Fate and Effects Division, and Health 

Canada Pesticide Management Regulatory Agency, Oct.15, 2012.

US EPA, 2013. Environmental Fate and Ecological Risk Assessment for Proposed Use of 

Methoxyfenozide on Herb Subgroup 19A (except chives), Dates, Sorghum, Fruiting Vegetable 

Group 8-10, Pome Fruit Group 11-10, Berry Subgroups 13-07 A, F & G, Tropical Tree Fruits 

AND Section 18 Emergency Exemption Petition for Use of Methoxyfenozide to Control Carob 

Moth on Dates. Environmental Fate and Effects Division, Office of Pesticide Programs, US 

EPA. DP Barcodes: 407284, 407808, 410683. June 13, 2013.

US EPA. 2013a. Methoxyfenozide: Review of Interim Report on Surface Water and Sediment 

Monitoring (MRID 49050001). Office of Chemical Safety and Pollution Prevention, Office of 

Pesticide Programs, From Environmental Fate and Effects Division (EFED) to Registration 

Division (RD); from C. Peck to M. Suarez. March 26, 2013.

US EPA. 2013b. Registration Review: Preliminary Problem Formulation for Environmental 

Fate, Ecological Risk, Endangered Species, and Human Health Drinking Water Exposure 

Assessments for Methoxyfenoxide. DP Barcode: D404482. Date: April 25, 2013.

US EPA, 2014. Guidance for Assessing Pesticide Risks to Bees. US EPA, Office of Pesticide 

Programs, Health Canada Pest Management Regulatory Agency, and California Department of 

Pesticide Regulation. June 19, 2014.

USDA Crop Profiles. Available online at: http://www.ipmcenters.org/cropprofiles/CP_form.cfm
51

Appendix A: Summary of Registered Uses of Methoxyfenozide (May, 2015)

Use

Method of 

Applicatio

n

Min 

Single 

App rate 

(lb a.i./A)

Max Single 

App Rate 

(lb a.i./A)

Max 

#Apps/ 

Year

Max App

rate/Year 

(lb a.i./ 

A/Yr)

MRI 

(days)

Reg 

Numbers

Brassica (Cole) Leafy 

Vegetables (Crop Group 5)2

Ground, 

aerial 0.078 0.234 6 1 4 62719-666

Bushberries (Subgroup (13-

07B1), Aronia Berry, 

Buffalo Currant, Chilena 

Giava, European Barberry, 

Highbush Cranberry, 

Honeysuckle, Jostaberry, 

Junerberry, Lingonberry, 

Native Currant, Salal, Sea 

Buck thorn, and Cultivars 

and/or Hybrids of Each

Ground, 

aerial 0.06 0.25 3 0.75 7 62719-442

Bushberries (Subrgroup 13B) Ground, 

aerial 0.078 0.234 3 0.75 7 62719-666

Cilantro Leaves, Brassica 

(Cole) Leafy Vegetables 

(Crop Group 5)2

, Leafy 

Vegetables (Crop Group 4)3

, 

Leaves of Root and Tuber 

Vegetables (Crop Group 2)4

, 

and Turnip Greens

Ground, 

aerial 0.06 0.25 NS 1 NS 62719-442

Cilantro Leaves Ground, 

aerial 0.078 0.234 5 1 4 62719-666

Citrus Fruits (Crop Group 

10-10)5 Ground 0.12 0.25 NS 1 14 62719-442

Citrus Fruits (Crop Group 

10-10)5 Ground 0.117 0.234 3 0.94 7 62719-442

Corn (Field, Sweet, Seed) Ground, 

aerial 0.06 0.25 NS 1 5 62719-442

Corn (Field, Sweet, Seed) Ground, 

aerial 0.078 0.234

3 - Field 

Corn

6 -

Sweet, 

Seed 

Corn

2, 4 62719-666

Cotton Ground, 

aerial 0.06 0.16 NS 1 10 62719-442

Cotton Ground, 

aerial 0.05 0.4 2 1 10, 14 62719-438

Cotton Ground, 

aerial 0.078 0.156 6 1 4 62719-666

Cranberry

Ground, 

aerial, 

chemigatio

n

0.16 0.25 NS 1 10 62719-442
52

Cranberry

Ground, 

aerial, 

chemigatio

n

0.137 0.234 6 1 7 62719-666

Cucurbit Vegetables (Crop 

Group 9)7

Ground, 

aerial 0.078 0.156 4 per season

1 7 62719-666

Cucurbit Vegetables (Crop 

Group 9)7

Ground, 

aerial 0.06 0.16 4 1 7 62719-442

Foliage of Legume 

Vegetables (Except Soybean)

Ground, 

aerial 0.078 0.234 4 1 7 62719-666

Fruiting Vegetables (Crop 

Group 8)8 and Okra

Ground, 

aerial 0.06 0.25 NS 1 7, 14 62719-442

Fruiting Vegetables (Crop 

Group 8)8 and Okra

Ground, 

aerial 0.078 0.234 6 1 4 62719-666

Globe Artichoke Ground, 

aerial 0.06 0.25 4 1 7 62719-442

Globe Artichoke Ground, 

aerial 0.078 0.234 4 1 7 62719-666

Grape Ground, 

aerial 0.117 0.234 5 0.75 4 62719-666

Grape Ground, 

aerial 0.12 0.25 NS 0.75 10, 18 62719-442

Grass Forage, Fodder, and 

Hay (Crop Group 17)

Ground, 

aerial 0.06 0.12 NS 0.5 NS 62719-442

Green Onion (Subgroup 3-

07B)9

Ground, 

aerial 0.06 0.12 6 1 10 62719-442

Green Onion, Leek, and 

Shallot

Ground, 

aerial 0.078 0.176 5 1 4 62719-666

Leafy Vegetables (Except 

Brassica) (Crop Group 4)

Ground, 

aerial 0.078 0.234 6 1 4 62719-666

Leaves of Root and Tuber 

Vegetables (Crop Group 2) 

and Turnip Greens

Ground, 

aerial 0.078 0.234 6 1 7 62719-666

Legume Vegetables 

(Succulent or Dried) (Crop 

Group 6)

Ground, 

aerial 0.078 0.234 1 , 0.47 7 62719-666

Legume Vegetables 

(Succulent or Dried) (Crop 

Group 6)10 and Foliage of 

Legume Vegetables (Except 

Soybean) (Subgroup 7A)11

Ground, 

aerial 0.06 0.25 4 1 7 62719-442
53

Nongrass Forage, Fodder, 

Straw and Hay (Crop Group 

18)12

Ground, 

aerial 0.06 0.12 NS 0.5 NS 62719-442

Ornamentals

Ground, 

aerial, 

convention

al spray, 

chemigatio

n

0.06 0.25 4 0.5 14 62719-442

Peanut Ground, 

aerial 0.09 0.16 3 1 7 62719-442

Peanut Ground, 

aerial 0.078 0.156 3 1 7 62719-666

Peppermint and Spearmint Ground, 

aerial 0.156 0.234 4 1 4 62719-666

Pineapple Ground 0.06 0.1 4 0.44 7 62719-442

Pome Fruits (Crop Group 

11)13

Ground, 

aerial 0.09 0.25 NS 1 10, 18 62719-442

Pome Fruits Ground, 

aerial 0.15 0.3 3 1 10, 14, 15, 18 62719-438

Pome fruits (Crop Group 11) Ground, 

aerial 0.088 0.25 4 1 10 62719-666

Pomegranate Ground, 

aerial 0.12 0.25 NS 1 14, 18 62719-442

Pomegranate Ground, 

aerial 0.117 0.234 3 0.547 10 62719-666

Popcorn Ground, 

aerial 0.06 0.12 NS 1 10 62719-442

Popcorn Ground, 

aerial 0.078 0.125 6 1 2, 4 62719-666

Root Vegetables14 Ground, 

aerial 0.12 0.25 NS 1, 0.5

(radishes) 14 62719-442

Root Vegetables (Subgroups 

1A, 1B) and Tuberous and 

Corm Vegetables (Except 

Potato) (Subgroup 1D)

Ground, 

aerial 0.088 0.234 3* 1, 0.94, 

0.1 14 62719-666

Soybean Ground, 

aerial 0.06 0.12 4 1 7 62719-442

Soybean Ground, 

aerial 0.078 0.125 4 0.545 4 62719-666

Spearmint and Peppermint Ground, 

aerial 0.16 0.25 NS 1 14, 21 62719-442
54

Stone Fruits -- Apricots, 

Nextarines, Peaches, Plums, 

Prunes, and Their Hybrids

Ground, 

aerial 0.12 0.25 NS

1 10, 14, 

18 62719

-442

Stone Fruits -- Cherries 

(Sweet and Sour)

Ground, 

aerial 0.12 0.25 NS 0.9 10, 14, 

18 62719

-442

Stone Fruits (Crop Group 12) Ground, 

aerial 0.117 0.234

417 62719-666

Strawberry Ground, 

aerial 0.09 0.19

11 10, 14 62719-442

Strawberry Ground, 

aerial 0.088 0.176

514 62719-666

Tree Nuts (Crop Group 14)16

and Pistachios -- Almonds

Ground, 

aerial 0.12 0.38 NS

1 10, 14, 

18 62719

-442

Tree Nuts (Crop Group 14)16

and Pistachios -- Almonds

Ground, 

aerial 0.117 0.352

417 62719-666

Tree Nuts (Crop Group 14)16

and Pistachios -- Hazelnuts

Ground, 

aerial 0.12 0.25 NS

1 10, 14, 

18, 21 62719

-442

Tree Nuts (Crop Group 14)16

and Pistachios -- Hazelnuts

Ground, 

aerial 0.117 0.234

417 62719-666

Tree Nuts (Crop Group 14)16

and Pistachios -- Pecans

Ground, 

aerial 0.06 0.12 NS

1 14 62719-442

Tree Nuts (Crop Group 14)16

and Pistachios -- Pecans

Ground, 

aerial 0.078 0.125

417 62719-666

Tree Nuts (Crop Group 14)16

and Pistachios -- Walnuts

Ground, 

aerial 0.12 0.38 NS

1 14, 21 62719-442

Tree Nuts (Crop Group 14)16

and Pistachios -- Walnuts

Ground, 

aerial 0.117 0.352

417 62719-666

Tree Nuts (Crop Group 14)16

and Pistachios -- Not Listed

Ground, 

aerial NS NS NS

1 10, 20 62719-442

Tree Nuts (Crop Group 14)16

and Pistachios -- Not Listed

Ground, 

aerial NS NS

417 62719-666

Tropical Tree Fruits17 Ground, 

aerial 0.16 0.25

51X18 62719-442

Tropical Tree Fruits -

Acerola, feijoa, guava, 

jaboticaba, passionfruit, 

starfruit, wax jambu

Ground, 

aerial 0.137 0.234

316 62719-666

Tropical Tree Fruits -

Avocado

Ground, 

aerial 0.137 0.234

316 62719-666

Tropical Tree Fruits - Black 

sapote, canistal, mamey 

sapote, mango, papaya, 

sapodilla, star apple

Ground, 

aerial 0.137 0.234

31 10 62719-666
55

Tropical Tree Fruits -

Longan, lychee, pulasan, 

rambutan, Spanish lime

Ground, 

aerial 0.137 0.234 3 1 10 62719-666

Tuberous and Corm 

Vegetables (except Potato) 

(Subgroup 1D)19

Ground, 

aerial 0.09 0.16 3 1 14 62719-442

Sweet Potato Ground, 

aerial 0.09 0.16 1 0.16 7 62719-442

Sweet Potato Ground, 

aerial 0.09 0.16 3 0.48 7 62719-442

Sweet Potato Ground, 

aerial 0.09 0.16 3 0.48 7 62719-442

Non-Bearing Citrus 

(Including Nurseries)

Ground, 

aerial 0.09 0.18 4 0.72 7, 14 62719-442

Citrus Fruits Ground, 

aerial 0.12 0.25 NS 1 14 62719-442

Dry Beans (Colorado) Aerial 0.12 0.25 NS 1 14 62719-442

Sugarbeet (Colorado) Aerial 0.12 0.25 NS 1 14 62719-442

Dry Beans (Wyoming) Aerial 0.12 0.25 4 1 7 62719-442

Sugarbeet (Wyoming) Aerial NS 1 14 62719-442

Dates Ground 0.16 0.31 NS 1 10 62719-442

Herbs (Fresh and Dried) 

(Except Chive)

Ground, 

Aerial 0.06 0.25 NS 1 10 62719-442

Caneberries Ground, 

Aerial 0.06 0.25 3 0.75 7 62719-442

Sorghum Ground, 

Aerial 0.12 0.16 NS 0.75 NS 62719-442

1Bushberries (subgroup 1307B) including black currant, elderberry, gooseberry high bush blueberry, huckleberry, lowbush 

blueberry, red currant

2 Brassica (cole) leafy vegetables (crop group 5) including broccoli, broccoli raab, Brussels sprouts, cabbage, cauliflower, cavalo 

broccolo, Chinese broccoli, Chinese cabbage (bok choy, napa), Chinese mustard cabbage (gai choy), collards, kale, kohlrabi, 

mizuna, mustard greens, mustard spinach, rape greens.

3Leafy vegetables (except Brassica) (crop group 4) including amaranth, arugula, cardoon, celery, celtuce, chervil, Chinese celery, 

corn salad, dandelion, dock, edible-leaved chrysanthemum, endive (escarole), florence fennel, garden cress, garden purslane, 

garland chrysanthemum, lettuce (head, leaf), New Zealand spinach, orach, parsley, radicchio, rhubarb, spinach, Swiss chard, 

upland cress, vine spinach, winter purslane.

4Leaves of root and tuber vegetables (crop group 2) including bitter cassava, black salsify, carrot, celeriac, chicory, dasheen, 

edible burdock, garden beet, parsnip, oriental radish, radish, rutabaga, sugarbeet, sweet cassava, sweet potato, tanier, true yam, 

turnip, and turnip-rooted chervil 5Citrus fruits (crop group 10-10) including Australian desert lime, Australian finger lime, Australian round lime, brown river 

finger lime, calamondin, citron, citrus hybrids, grapefruit, Japanese summer grapefruit, kumquat, lemon, lime, Mediterranean 

mandarin, mount white lime, New Guinea wild lime, pummelo, russell river lime, satsuma mandarin, sour orange, sweet lime, 

sweet orange, tachibana orange, Tahiti lime, tangelo, tangerine (Mandarin), tangor, trifoliate orange, uniq fruit, cultivars, varieties 

and/or hybrids of these

6Suppression only. Use a higher rate in the rate range and ensure thorough coverage. Tank mixing Intrepid® 2F with other 

products registered for fall armyworm control in cotton (e.g., pyrethroids, spinosad, or others) has been shown to improve 

control. Consult your Dow AgroSciences’ representative, extension service specialist, certified crop advisor or state agricultural 

experiment station for any additional local use recommendations for your area.

7Cucurbit vegetables (crop group 9) including balsam apple, balsam pear, bitter melon, chayote (fruit), Chinese cucumber, 

Chinese waxgourd (Chinese preserving melon), citron melon, cucumber, edible gourd (including Chinese okra, cucuzza, 

hechima, hyotan), gherkin, muskmelon (including cantaloupe, casaba, crenshaw melon, golden pershaw melon, honey balls, 

honeydew melon, mango melon, persian melon, pineapple melon, santa claus melon, snake melon, true cantaloupe), pumpkin, 

summer squash (including crookneck squash, scallop squash, straightneck squash, vegetable marrow, zucchini), winter squash 

(including acorn squash, butternut squash, calabaza, hubbard squash, spaghetti squash), watermelon
56

8 Fruiting vegetables (crop group 8) including eggplant, groundcherry, pepino, pepper (bell, chili, cooking, sweet), pimento, 

tomatillo, tomato

9Green onion (subgroup 3-07B) including beltsville bunching onion, Chinese chive (fresh leaves), chive (fresh leaves), elegans 

hosta, fresh onion, fritillaria leaves, green onion, kurrat, lady’s leek, leek, macrostem onion, shallot (fresh leaves), tree onion 

(tops), wild leek

10Legume vegetables (succulent or dried) (crop group 6) including asparagus bean, blackeyed pea, Cajanus spp. (pigeon pea), 

Chinese longbean, Cicer arietinum (chick peas, garbanzo beans), cowpea, green lima bean, jackbean, Lens spp. (lentils), Lupinus 

spp. (grain lupine, sweet lupine, white lupine, white sweet lupine), moth bean, Phaseolus spp. (kidney beans, lima beans, mung 

beans, navy beans, pinto beans, snap beans, waxbeans), Pisum spp. (dwarf pea, edible-pod pea, English pea, field pea, garden 

pea, green pea), runner bean, snap bean, snow pea, soybean (immature seed), southern pea, succulent broad bean, sugar snap pea, 

sword bean, Vicia faba (broad beans, fava beans); Vigna spp. (asparagus beans, blackeyed pea, cowpeas), wax bean, yardlong 

bean

11Foliage of legume vegetables (except soybean) (subgroup 7A) including any cultivar of bean and field pea (except soybean)

12Nongrass forage, fodder, straw and hay (crop group 18) including alfalfa, clover, crown vetch, kudzu, lespedeza, lupin, milk 

vetch, sainfoin, trefoil, velvet bean, vetch

13Pome fruits (crop group 11) including apple, crabapple, loquat, mayhaw, pear, pear (oriental), quince

14Root vegetables (subgroups 1A, 1B) including black salsify, carrot, celeriac, chicory, edible burdock, garden beet, ginseng, 

horseradish, parsnip, oriental radish, radish, rutabaga, salsify, skirret, Spanish salsify, sugarbeet, turnip, turnip-rooted chervil, and 

turnip-rooted parsley 15Stone fruits (crop group 12) including apricot, cherries (sweet, sour), chickasaw plum, damson plum, Japanese plum, nectarine, 

peach, plum, plumcot, prune (fresh)

16Tree nuts (crop group 14) including almond, beech nut, Brazil nut, butternut, cashew, chestnut, chinquapin, filbert (hazelnut), 

hickory nut, macadamia (bush) nut, pecan, pistachio, walnut (black and English)

17Acerola, avocado, black sapote, canistal, feijoa, guava, jaboticaba, longan, lychee, mamey sapote, mango, papaya, passionfruit, 

pulasan, rambutan, sapodilla, Spanish lime, star apple, starfruit, wax jambu 18Acerola, Feijoa, Guava, Jaboticaba, Passionfruit, Starfruit, Wax Jambu: Preharvest Interval: Do not apply within 3 days of 

harvest. Minimum Re-treatment Interval: 6 days Avocado: Preharvest Interval: Do not apply within 2 days of harvest. Minimum 

Re-treatment Interval: 6 days Black Sapote, Canistal, Mamey Sapote, Mango, Papaya, Sapodilla, Star Apple: Preharvest Interval: 

Do not apply within 3 days of harvest. Minimum Re-treatment Interval: 10 days Longan, Lychee, Pulasan, Rambutan, Spanish 

Lime: Preharvest Interval: Do not apply within 14 days of harvest. Minimum Re-treatment Interval: 10 days 19Tuberous and corm vegetables (except potato) (subgroup 1D) including arracacha, arrowroot, bitter cassava, chayote (root), 

Chinese artichoke, chufa, dasheen, edible canna, ginger, Jerusalem artichoke, leren, sweet cassava, sweet potato, tanier, true yam, 

turmeric, yam bean

*Arracacha, arrowroot, bitter cassava, chayote root, Chinese artichoke, chufa, dasheen, edible canna, ginger, 

Jerusalem artichoke, leren, sweet cassava, sweet potato, tanier, true yam, turmeric, yam bean, celeriac, edible 

burdock, Oriental radish, rutabaga, turnip)

4 (Garden beet, sugar beet, black salsify, carrot, chicory, ginseng, horseradish, parsnip, salsify, skirret, Spanish 

salsify, turnip-rooted chervil, turnip-rooted parsley, radish
57

APPENDIX B: Methoxyfenozide and Its Environmental Degradates

Code Name/ 

Synonym Chemical Name Chemical Structure Study Type

Ref.

(MRID)

Max%AR 

(day)

Final %AR 

(study length)

PARENT

Methoxyfenozide

CAS No.: 161050-

58-4

Formula: 

C22H28N2O3

MW: 368 g/mol

Smile string: 

Cc1c(OC)cccc1C(=

O)NN(C(C)(C)C)C

(=O)c2cc(C)cc(C)c

2

MINOR TRANSFORMATION PRODUCTS

RH-117236

CAS No.:

Formula:

C21H26N2O3

MW: 354.45

Smile string: 

CC1=C(C=CC=C1

O[H])C(=O)NN(C(

C)(C)C)C(=O)C2=

CC(=CC(=C2)C)C

Aerobic 

aquatic 

study

446178-09

In CA, 

15.8% (91 

d)

In TX, 6.7% 

(60 d)

In Ca, 3% (365 d)

In TX, 1% (365 d)

RH-131154

CAS No: 

Formula:

C22H26N2O5

MW: 398.46

Smile string: 

CC1=C(C=CC=C1

OC)C(=O)NN(C(C

)(C)C)C(=O)C2=C

C(=CC(=C2)C(O[H

])=O)C

Aerobic 

aquatic 

study

446178-09 <1% (365 

d) <1% (365 d)

Anaerobic 

aquatic 

study

446178-10 1.1% (119 

d) 0.61% (364 d)

Aerobic soil 

metabolism

446178-08

446178-07

441444-32

-- 1-3% (365 d)

CO2

CAS No: 124-38-9

Formula: CO2

MW: 44.01 g/mol

Smile string: 

C(=O)=O

Aerobic 

aquatic 

study

446178-09 -- <6% (365)

Anaerobic 

aquatic 

study

446178-10 -- 3.2% (364)

Aerobic soil 

metabolism

446178-08

446178-07

441444-32

-- 2-5% (365 d)
58

APPENDIX C: Summary of the Available Eco-Toxicity Data for Methoxyfenozide.

TABLE C.1. Summary of Submitted Toxicity Data for Methoxyfenozide and Aquatic 

Animals.

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

LC50 >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

48-hour 

Acute 

Toxicity

Waterflea

Daphnia magna

EC50 = 3.7 mg 

a.i./L

Moderately 

Toxic 441444-11 Acceptable

Estimate 

based on 

Acute-toChronic 

Ratio1

Midge 

Chironomus 

riparius

EC50 = 0.061 mg 

a.i./L

(mortality)

Very highly 

toxic N/A1 N/A1

Chronic 

Toxicity

Waterflea

Daphnia magna

NOAEC = 0.20

mg a.i./L

LOAEC = 0.39

mg a.i./L

(survival)

N/A 446177-14 Acceptable

Chronic 

Effects on 

Midge 

Larvae

Midge 

Chironomus 

riparius

NOAEC=0.0031

mg a.i./L (pore 

water)

LOAEC=0.0063 

mg a.i./L (pore 

water)

(Delayed 

emergence and 

development)

N/A 450328-01 Supplemental

Estuarine/ 

Marine Fish

96-Hour 

Acute 

Toxicity

Sheepshead 

minnow

Cyprinodon 

variegatus

96-hr LC50 >2.8 

mg a.i./L

Moderately 

Toxic 441444-12 Acceptable

Early Life 

Stage 

Toxicity

NOAEC = 1.5 mg 

a.i./L

LOAEC = 2.6 mg 

a.i./L

(growth)

N/A 446177-12 Currently under 

review in EFED
59

Taxonomic 

Group

Study 

Type

Surrogate 

Species

Toxicity Value

(all units in 

terms of 

measured active 

ingredient)

Acute Toxicity 

Classification Source 

(MRID)

Study 

Classification

Estuarine/ 

Marine 

Invertebrates

96-Hour 

Shell 

Depositio

n

Eastern oyster

Crassostrea 

virginica

96-hr EC50 = 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)

EC50 >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 This endpoint is based on an acute to chronic ratio (ACR) using acute and chronic data from daphnids and chronic 

data from midges.
60

TABLE C.2. Summary of Available Toxicity Data for Methoxyfenozide and Terrestrial 

Animals.

Taxonomi

c 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

LD50 >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

LC50 >5,870

mg a.i./kg-diet

No effects at 

highest treatment 

level tested

Practically 

Non-Toxic 441444-07 Acceptable

Avian 

Reproducti

ve Toxicity

Northern 

bobwhite quail

Colinus 

virginianus

NOAEC=520 mg 

a.i./kg-diet

N/A 446177-11 Acceptable

Mammals

Acute oral 

Toxicity

Rat

Rattus norvegicus

LD50 >5,000 mg 

a.i./kg-bw

Acute Toxicity 

Category 4 441444-15 Acceptable

2-

Generation 

Reproducti

on Toxicity

Rat

Rattus norvegicus

NOAEC = 20,000 

ppm diet

(1552 mg/kg)

(Survival)

N/A 446177-27 Acceptable

Terrestrial 

Invertebrat

es

Acute 

Contact 

Toxicity

Honey bee

Apis mellifera

LD50 >100 μg

a.i./bee

Practically 

Non-Toxic 441444-29 Acceptable

Dietary 

Toxicity

LC50 > 100 μg

a.i./bee

Practically 

Non-Toxic 446177-17 Supplemental

Brood 

Study

NOAEL = 101 

mg a.i./L N/A 450655-01 Supplemental
61

Appendix D: Example Summary Output of T-REX (Tree Nuts Use)

TREX MODEL 

INPUTS

You must enable macros for this spreadsheet to 

work correctly

Chemical Identity and Application Information

Application 

No. Rate Day of Application

Chemical Name:

Methoxyfenozide

Application 

Rate (lb 

ai/acre) 1 0.38 0

Seed Treatment? 

(Check if yes)

FALSE Seeding Rate 

(lbs/acre) 2 0.38 10

 Use: Tree nuts 3 0.24 20

Product name 

and form: 4

% A.I. (leading 

zero must be 

entered for 

formulations <1% 

a.i.): 100.00% 5

Application Rate 

(lb ai/acre) 0.38 6

Half-life (days): 35 7

Application 

Interval (days): 10 8

Number of 

Applications: 3 9

Are you assessing 

applications with 

variable rates or 

intervals? yes 10

You MUST specify application day in Columns F and G - you may enter up to 30 

applications 11

Assessed Species Inputs (optional, use defaults for RQs for national level 

assessments) 12

What body 

weight range is 

assessed (grams)? Birds

Mammal

s 13

Small 20 15 14

Medium 100 35 15

Large

1000 1000

16

Note: Sources of wildlife diet are assumed to be available for less than 

one year for this model.

Endpoints
62

Avian

Endpoint

Toxicity 

value

Indicate test 

species 

below

Optional 

Test 

Organism 

Body 

weight (g)

Optional Test 

Species Name

LD50 (mg/kg-bw)

2250.00 1

LC50 (mg/kg-diet)

5870.00 1

NOAEL (mg/kg-bw)

1

NOAEC (mg/kg-diet)

520.00 1

Enter the Mineau et al. Scaling Factor 1.15

Mammalian

Acute Study Chronic Study

Size (g) of mammal used in toxicity study

Default rat body weight is 350 grams 350 350

Endpoint

Toxicity 

value

Reference 

(MRID)

LD50 (mg/kg-bw) 5000.00 441444-15

LC50 (mg/kg-diet)

Reported Chronic Endpoint 20000.0

0

44617727 2

Is estimated daily dose (mg/kg-bw) 

reported from the available chronic 

mammal study? (yes or no)

no

Enter daily dose (mg/kg-bw)

Estimated Chronic Daily Dose 

Equivalent to reported Chronic 

Dietary Endpoint

1000

mg/kg-bw 

based on 

standard 

FDA lab rat 

conversion
63

Summary of Risk Quotient Calculations Based on Upper Bound Kenaga EECs

Table X. Upper Bound Kenaga, Acute Avian Dose-Based Risk Quotients

Size Class

(grams)

Adjusted

LD50

EECs and RQs

Short Grass Tall Grass Broadleaf 

Plants

Fruits/Pods/

Seeds Arthropods Granivore

EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ

20 1620.97 258.97

0.1

6 118.70 0.07

145.

67

0.

09

16.1

9 0.01 101.43 0.06 3.60 0.00

100 2063.57 147.68

0.0

7 67.69 0.03

83.0

7

0.

04 9.23 0.00 57.84 0.03 2.05 0.00

1000 2914.87 66.12

0.0

2 30.30 0.01

37.1

9

0.

01 4.13 0.00 25.90 0.01 0.92 0.00

Table X. Upper Bound Kenaga, Subacute Avian Dietary Based Risk Quotients

LC50

EECs and RQs

Short Grass Tall Grass Broadleaf Plants Fruits/Pods/Seeds Arthropods

EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ

5870

227.3

9 0.04

104.2

2

0.0

2 127.91 0.02 14.21 0.00 89.06 0.02

Size class not used for dietary risk quotients 

Table X. Upper Bound Kenaga, Chronic Avian Dietary Based Risk Quotients

NOAEC 

(ppm)

EECs and RQs

Short Grass Tall Grass Broadleaf 

Plants Fruits/Pods/Seeds Arthropods

EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ

520

227

.39 0.44 104.22 0.20 127.91

0.2

5 14.21 0.03 89.06 0.17

Size class not used for dietary risk quotients

Table X. Upper Bound Kenaga, Acute Mammalian Dose-Based Risk Quotients 

Size Class

(grams)

Adjus

ted

LD50 EECs and RQs
64

Short Grass Tall Grass Broadleaf 

Plants Fruits/Pods/Seeds Arthropods

EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ EEC

15

10989.

15 216.80 0.02 99.37 0.01

121.9

5 0.01 13.55 0.00 84.912 0.0077 3.011

35

8891.4

0 149.84 0.02 68.67 0.01 84.28 0.01 9.36 0.00 58.6856 0.0066 2.08

1000

3845.8

0 34.74 0.01 15.92 0.00 19.54 0.01 2.17 0.00 13.6065 0.0035 0.482

Table X. Upper Bound Kenaga, Chronic Mammalian Dietary Based Risk Quotients

NOAEC 

(ppm) EECs and RQs

Short Grass Tall Grass Broadleaf Plants Fruits/Pods/Seeds/Large 

Insects Arthropods

EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ

20000

227.

39 0.01

104.

22 0.01 127.91 0.01 14.21 0.00 89.06 0.00

Size class not used for dietary risk quotients 

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

Size Class

(grams)

Adjusted 

NOAEL

EECs and RQs

Short Grass Tall Grass Broadleaf Plants Fruits/Pods/Seeds Arthropods

EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ EEC

15 2197.83 216.80 0.10 99.37 0.05 121.95 0.06 13.55 0.01 84.91 0.04 3.01

35 1778.28 149.84 0.08 68.67 0.04 84.28 0.05 9.36 0.01 58.69 0.03 2.08

1000 769.16 34.74 0.05 15.92 0.02 19.54 0.03 2.17 0.00 13.61 0.02 0.48
65

Upper Bound Kenaga, Acute Mammalian Dose-Based Risk Quotients 

Size 

Class

(gra

ms)

Adjus

ted

LD50

EECs and RQs

Short Grass Tall Grass Broadleaf Plants Fruits/Pods/Seeds Granivore

EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ

15

1098

9.15 82.76

0.0

1 37.93 0.00 46.55 0.00 5.17 0.00 1.1495 0.0001

35

8891.

40 57.20

0.0

1 26.22 0.00 32.18 0.00 3.58 0.00 0.7945 9E-05

1000

3845.

80 13.26

0.0

0 6.08 0.00 7.46 0.00 0.83 0.00 0.1842 5E-05

Upper Bound Kenaga, Chronic Mammalian Dietary Based Risk Quotients

NOAEC 

(ppm)

EECs and RQs

Short Grass Tall Grass Broadleaf 

Plants Fruits/Pods/Seeds/Large Insects

EEC RQ EEC RQ EEC RQ EEC RQ

8000 86.81 0.01

39.7

9 0.00 48.83 0.01 5.43 0.00

Size class not used for dietary risk quotients 

Upper Bound Kenaga, Chronic Mammalian Dose-Based Risk Quotients

Size 

Class

(grams)

Adjusted 

NOAEL

EECs and RQs

Short Grass Tall Grass Broadleaf Plants Fruits/Pods/

Seeds Granivore

EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ

15 879.13 82.76 0.09 37.93 0.04 46.55 0.05 5.17 0.01 1.15 0.00

35 711.31 57.20 0.08 26.22 0.04 32.18 0.05 3.58 0.01 0.79 0.00

1000 307.66 13.26 0.04 6.08 0.02 7.46 0.02 0.83 0.00 0.18 0.00
66

Appendix E: Output of TerrPlant Model Results

TerrPlant v. 1.2.2

Green values signify user inputs (Tables 1, 2 and 4). 

Input and output guidance is in popups indicated by red arrows.

Table 1. Chemical Identity.

Chemical Name Methoxyfenozide

PC code 121027

Use Cotton

Application Method Aerial

Application Form Spray 

Solubility in Water 

(ppm) 3.3

Table 2. Input parameters used to derive EECs.

Input Parameter Symbol Value Units

Application Rate A 0.4 lb ai/A

Incorporation I 1 none

Runoff Fraction R 0.01 none

Drift Fraction D 0.05 none

Table 3. EECs for Methoxyfenozide. Units in lb ai/A.

Description Equation EEC

Runoff to dry areas (A/I)*R 0.004

Runoff to semi-aquatic areas (A/I)*R*10 0.04

Spray drift A*D 0.02

Total for dry areas ((A/I)*R)+(A*D) 0.024

Total for semi-aquatic areas ((A/I)*R*10)+(A*D) 0.06

Table 4. Plant survival and growth data used for RQ derivation. Units are in lb ai/A.

Seedling Emergence Vegetative Vigor

Plant type EC25 NOAEC EC25 NOAEC 

Monocot 1.94 1.94 1.97 1.97

Dicot 1.94 0.98 1.97 0.97

Table 5. RQ values for plants in dry and semi-aquatic areas exposed to Methoxyfenozide through 

runoff and/or spray drift.*

Plant Type Listed Status Dry Semi-Aquatic Spray Drift

Monocot non-listed <0.1 <0.1 <0.1

Monocot listed <0.1 <0.1 <0.1

Dicot non-listed <0.1 <0.1 <0.1

Dicot listed <0.1 <0.1 <0.1

*If RQ > 1.0, the LOC is exceeded, resulting in potential for risk to that plant group.
67

Appendix F: Output Value of NC cotton scenario in the pond

Summary of Water Modeling of Methoxyfenozide and the USEPA Standard Pond

Estimated Environmental Concentrations for Methoxyfenozide are presented in Table 1 for the USEPA standard pond 

with the NCcottonSTD field scenario. A graphical presentation of the year-to-year peaks is presented in Figure 1. 

These values were generated with the Surface Water Concentration Calculator (SWCC Version 1.106). Critical input 

values for the model are summarized in Tables 2 and 3.

This model estimates that about 4.9% of Methoxyfenozide applied to the field eventually reaches the water body. The 

main mechanism of transport from the field to the water body is by runoff (64.2% of the total transport), followed by 

spray drift (25.5%) and erosion (10.4%).

In the water body, pesticide dissipates with an effective water column half-life of 2684.7 days. (This value does not 

include dissipation by transport to the benthic region; it includes only processes that result in removal of pesticide 

from the complete system.) The main source of dissipation in the water column is metabolism (effective average halflife = 2765.8 days) followed by volatilization (91570.1 days).

In the benthic region, pesticide dissipation is negligible (3480.8 days). The main source of dissipation in the benthic 

region is metabolism (effective average half-life = 3480.8 days). The vast majority of the pesticide in the benthic 

region (98.15%) is sorbed to sediment rather than in the pore water.

Table 1. Estimated Environmental Concentrations (ppb) for Methoxyfenozide.

Peak (1-in-10 yr) 185.

4-day Avg (1-in-10 yr) 185.

21-day Avg (1-in-10 yr) 183.

60-day Avg (1-in-10 yr) 182.

365-day Avg (1-in-10 yr) 176.

Entire Simulation Mean 123.

Table 2. Summary of Model Inputs for Methoxyfenozide.

Scenario NCcottonSTD

Cropped Area Fraction 1

Koc (ml/g) 490

Water Half-Life (days) @ 25 °C 1559

Benthic Half-Life (days) @ 25 °C 1962

Photolysis Half-Life (days) @ 40 °Lat 0

Hydrolysis Half-Life (days) 0

Soil Half-Life (days) @ 25 °C 960

Foliar Half-Life (days) 0

Molecular Wt 368

Vapor Pressure (torr) 2e-8

Solubility (mg/l) 3.3

Table 3. Application Schedule for Methoxyfenozide.
68

Date (Mon/Day) Type Amount (kg/ha) Eff. Drift

7/18 Foliar 0.45 0.95 0.125

7/28 Foliar 0.45 0.95 0.125

8/7 Foliar 0.22 0.95 0.125

Figure 1. Yearly Peak Concentrations
69

Appendix G. Output of KABAM Model for Methoxyfenozide

Table G1. Estimated concentrations of Methoxyfenozide in ecosystem components.

Ecosystem Component

Total 

concentration 

(μg/kg-ww)

Lipid 

normalized 

concentration 

(μg/kg-lipid)

Contribution 

due to diet 

(μg/kg-ww)

Contribution 

due to 

respiration 

(μg/kg-ww)

Water (total)* 178 N/A N/A N/A

Water (freely dissolved)* 178 N/A N/A N/A

Sediment (pore water)* 181 N/A N/A N/A

Sediment (in solid)** 3,548 N/A N/A N/A

Phytoplankton 43,774 2188680 N/A 43,773.60

Zooplankton 32,147 1071561 57.01 32,089.82

Benthic Invertebrates 35,172 1172402 148.48 35,023.59

Filter Feeders 23,180 1158985 95.86 23,083.85

Small Fish 45,566 1139159 613.60 44,952.77

Medium Fish 46,030 1150747 1,164.09 44,865.78

Large Fish 46,798 1169955 2,097.69 44,700.50

* Units: μg/L; **Units: μg/kg-dw

0

5000

10000

15000

20000

25000

30000

35000

40000

45000

50000

Zooplankton Benthic

Invertebrates

Filter Feeders Small Fish Medium Fish Large Fish

Concentration (μg/kg)

Trophic Level

Figure 1. Total pesticide concentration 

per trophic level

Contribution due to respiration (μg/kg-ww)

Contribution due to diet (μg/kg-ww)
70

Table G2. Total BCFand BAF values of Methoxyfenozide in 

aquatic trophic levels.

Trophic Level

Total BCF 

(μg/kgww)/(μg/L)

Total BAF 

(μg/kgww)/(μg/L)

Phytoplankton 253 246

Zooplankton 180 181

Benthic Invertebrates 197 198

Filter Feeders 130 130

Small Fish 253 256

Medium Fish 253 259

Large Fish 253 263

Table G3. Lipid-normalized BCF, BAF, BMF and BSAF values of Methoxyfenozide in aquatic 

trophic levels.

Trophic Level

BCF 

(μg/kglipid)/(μg/L)

BAF 

(μg/kglipid)/(μg/L)

BMF 

(μg/kglipid)/(μg/kglipid)

BSAF 

(μg/kglipid)/(μg/kgOC)

Phytoplankton 12640 12296 N/A 25

Zooplankton 6011 6020 0.49 12

Benthic Invertebrates 6565 6587 1.09 13

Filter Feeders 6490 6511 1.08 13

Small Fish 6328 6400 1.02 13

Medium Fish 6328 6465 1.00 13

Large Fish 6322 6573 1.02 13

Table G4. Calculation of EECs for mammals and birds consuming fish contaminated by Methoxyfenozide.

Wildlife Species Biological Parameters EECs (pesticide intake)

Body

Weight

(kg)

Dry Food 

Ingestion 

Rate (kg-dry 

food/kgbw/day)

Wet Food 

Ingestion 

Rate (kg-wet 

food/kgbw/day)

Drinking 

Water

Intake

(L/d)

Dose Based 

(mg/kgbw/d)

Dietary 

Based 

(ppm)

Mammalian

fog/water shrew 0.02 0.140 0.585 0.003 20.609 35.17

rice rat/star-nosed 

mole 0.1 0.107 0.484 0.011 16.785 34.64

small mink 0.5 0.079 0.293 0.048 13.520 46.03

large mink 1.8 0.062 0.229 0.168 10.565 46.03
71

small river otter 5.0 0.052 0.191 0.421 8.810 46.03

large river otter 15.0 0.042 0.157 1.133 7.367 46.80

Avian

sandpipers 0.0 0.228 1.034 0.004 35.9629 34.75

cranes 6.7 0.030 0.136 0.211 4.7493 34.91

rails 0.1 0.147 0.577 0.010 23.3327 40.37

herons 2.9 0.040 0.157 0.120 6.3980 40.60

small osprey 1.3 0.054 0.199 0.069 9.1884 46.03

white pelican 7.5 0.029 0.107 0.228 4.9987 46.80

Table G5. Calculation of toxicity values for mammals and birds consuming 

fish contaminated by Methoxyfenozide.

Wildlife Species

Toxicity Values

Acute Chronic

Dose 

Based 

(mg/kgbw)

Dietary 

Based 

(mg/kg-diet)

Dose Based 

(mg/kg-bw)

Dietary 

Based 

(mg/kg-diet)

Mammalian

fog/water shrew 10499.51 N/A 2099.90 20000

rice rat/star-nosed 

mole 7122.50 N/A 1424.50 20000

small mink 4695.52 N/A 939.10 20000

large mink 3320.24 N/A 664.05 20000

small river otter 2571.84 N/A 514.37 20000

large river otter 1954.18 N/A 390.84 20000

Avian

sandpipers 1620.97 5870.00 N/A 520

cranes 3877.31 5870.00 N/A 520

rails 1956.07 5870.00 N/A 520

herons 3419.63 5870.00 N/A 520
72

small osprey 3014.09 5870.00 N/A 520

white pelican 3943.47 5870.00 N/A 520

Table G6. Calculation of RQ values for mammals and birds consuming fish 

contaminated by Methoxyfenozide.

Wildlife Species

Acute Chronic

Dose 

Based

Dietary 

Based

Dose Based Dietary 

Based

Mammalian

fog/water shrew 0.002 N/A 0.010 0.002

rice rat/star-nosed 

mole 0.002 N/A 0.012 0.002

small mink 0.003 N/A 0.014 0.002

large mink 0.003 N/A 0.016 0.002

small river otter 0.003 N/A 0.017 0.002

large river otter 0.004 N/A 0.019 0.002

Avian

sandpipers 0.022 0.006 N/A 0.067

cranes 0.001 0.006 N/A 0.067

rails 0.012 0.007 N/A 0.078

herons 0.002 0.007 N/A 0.078

small osprey 0.003 0.008 N/A 0.089

white pelican 0.001 0.008 N/A 0.090