with details regarding the chemical properties of hexaflumuron, its application in an enclosed 

system (i.e., bait station), and further characterization of the consumption of subterranean 

termites by non-target mammals and birds, EFED does not expect the current use of 

hexaflumuron as an enclosed termiticide bait to contribute to ecological risk in aquatic or 

terrestrial ecosystems. 

EFED has recommended that the registrant amend labels to remove the statement directing users 

to add a sugary sports drink (used to enhance feeding and to add moisture) to the bait in order to 

reduce the likelihood that non-target terrestrial invertebrates become exposed to hexaflumuron.1

 

It is not clear whether hexaflumuron labels have been amended to have the sports drink 

suggestion removed, but EFED reiterates the recommendation to remove this suggestion to 

reduce hexaflumuron exposure to non-target invertebrates. 

Finally, given hexaflumuron’s persistence and bioaccumulation potential, EFED recommends 

that labels carry a statement directing users to retrieve and responsibly dispose of bait stations 

following use. Leaving used bait stations containing bait matrix in the ground could lead to 

contaminated soil. 

 

1 Hexaflumuron: Updated Review of Waiver Request for Pollinator Field Testing (OCSPP Guideline 850.3040).

D398118. 3/22/12.
-Page 2 of 36- 

Environmental Fate and Ecological Risk Assessment

for the Registration Review of Hexaflumuron 

1-(3,5-dichloro-4-(1,1,2,2-tetrafluoroethoxy)phenyl) -3-(2,6-difluorobenzoyl) urea

(Hexaflumuron)

CAS 86479-06-3 PC Code 118202 

18 March 2014 

Prepared by

Mary Clock-Rust, Biologist

Chuck Peck, Environmental Engineer 

U.S. Environmental Protection Agency

Office of Pesticide Programs

Environmental Fate and Effects Division (EFED)

Environmental Risk Branch IV

1200 Pennsylvania Ave., NW

Mail Code 7507P

Washington, DC 20460 Reviewed by

Thomas Steeger, Ph.D., Senior Science Advisor

Jim Carleton, Ph.D., Senior Scientist

Sarah Winfield, Acting Branch Chief
-Page 3 of 36- 

Table of Contents

1. Executive Summary ........................................................................................................................................... 4

2. Problem Formulation ....................................................................................................................................... 5

2.1. Nature of Regulatory Action.................................................................................................................... 5

2.2. Stressor Source and Distribution ............................................................................................................ 5

2.2.1. Nature of the Chemical Stressor ........................................................................................................... 5

2.3. Receptors .................................................................................................................................................. 8

2.3.1. Aquatic and Terrestrial Effects........................................................................................................ 8

2.3.2. Ecosystems Potentially at Risk........................................................................................................ 9

2.4. Assessment Endpoints.............................................................................................................................. 9

2.5. Conceptual Model ..................................................................................................................................... 9

2.5.1. Risk Hypothesis................................................................................................................................. 10

2.5.2. Conceptual Diagram .........................................................................................................................10

2.6. Analysis Plan ...........................................................................................................................................11

2.6.1. Measures of Exposure....................................................................................................................11

2.6.2. Measures of Effect..........................................................................................................................12

2.6.3. Integration of Exposure and Effects.............................................................................................12

3. Analysis............................................................................................................................................................13

3.1 Use Characterization...................................................................................................................................13

3.2. Exposure Characterization....................................................................................................................14

3.2.1. Environmental Fate and Transport Characterization................................................................. 14

3.2.3. Measures of Terrestrial Exposure..................................................................................................15

Equations Used to Calculate EECs in Table 3.2............................................................................................16

3.3. Ecological Effects Characterization......................................................................................................16

3.3.1. Aquatic Toxicity Characterization................................................................................................. 17

3.3.2. Terrestrial Effects Characterization..............................................................................................17

3.3.3. Review of Incident Data..................................................................................................................19

4. Risk Characterization......................................................................................................................................20

4.1. Risk Estimation.......................................................................................................................................20

4.2. Risk Description......................................................................................................................................21

4.3 Risk Conclusions.....................................................................................................................................24

5. Federally Threatened and Endangered (Listed) Species of Concern..........................................................25

6. Endocrine Disruptor Screening Program......................................................................................................26

7. References.........................................................................................................................................................27
-Page 4 of 36- 

1. Executive Summary

The preliminary risk assessment (PRA) examines the potential ecological risks associated with 

labeled uses of hexaflumuron, a benzoylphenylurea compound used to control termites. This

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

transport, and ecological effects data for hexaflumuron. 

Hexaflumuron is a chitin synthesis inhibitor that has relatively low solubility in water and low 

mobility in soils. The compound is subject to biotic degradation; however, it is contained within 

plastic bait stations which are likely to protect the compound from many routes of degradation. 

Hexaflumuron is used exclusively in containerized bait stations, both above and below ground. 

Hexaflumuron's low solubility in water, high octanol-water partition coefficient, and predicted 

slight mobility in soil indicate that hexaflumuron will not substantially dissolve in moisture that 

may enter the bait stations, so the potential for the chemical leaching from bait stations is 

expected to be low. Any hexaflumuron that does leach from bait stations is expected to bind 

readily to most soils. As a precaution, current label restrictions prohibit use of the bait stations 

“in depressions, low areas, near ponds, streams, springs, other water sources, or near 

downspout openings when the bait or its hexaflumuron contents could be washed out of the bait 

station into water at or near the surface of the ground”. These restrictions should further reduce 

the chance for hexaflumuron residues to migrate to surface or ground water. Therefore, given 

the application method of hexaflumuron (i.e., bait station) and its chemical properties, it is 

assumed that movement of hexaflumuron via runoff and long-range atmospheric transport have a 

low likelihood of contributing to ecological risk in aquatic ecosystems. In addition, spray drift 

will not occur because the product is contained in bait stations. 

Also, in this assessment, it is assumed that the plastic bait station limits the availability of 

hexaflumuron to non-target organisms. The entrances to the bait stations have been configured 

to be large enough (2.5 mm) to allow termites to enter while being small enough to prevent entry 

by most native ground-dwelling bees and other terrestrial invertebrates.2

 Additionally, foraging 

habits (i.e., use of cellulose materials as food) and the placement locations of the bait station (i.e., 

residential and urbanized areas) reduce the likelihood that native ground-dwelling bees and nontarget terrestrial invertebrates would come into contact with hexaflumuron. 

Hexaflumuron is very highly toxic to aquatic invertebrates on an acute exposure basis, 

practically non-toxic to terrestrial invertebrates3, and practically non-toxic to birds and mammals 

on an acute oral exposure basis; the compound is slightly toxic to birds on a subacute dietary 

exposure basis. On a chronic exposure basis, hexaflumuron resulted in reduced survival in birds

(mallard duck and bobwhite quail) and reduced growth (pup body weights) in rats. 

 

2

Hexaflumuron: Updated Review of Waiver Request for Pollinator Field Testing (OCSPP Guideline 850.3040).

D398118. 3/22/12.

3 In acute toxicity tests with adult honeybees (Apis mellifera), the formulated product (Consult® 100 SC) was 

categorized as moderately toxic. However, the TGAI is classified as practically non-toxic to bees, indicating that 

the formulated product is more toxic than TGAI to adult honeybees.
-Page 5 of 36- 

The screening-level risk assessment identified potential chronic risk to listed and non-listed birds 

(all size classes). Also, the risk assessment identified potential chronic risk to small (15 g) and 

medium (35 g) sized mammals. However, these screening level risk estimates are calculated 

using conservative assumptions regarding the toxicity of hexaflumuron and the potential 

availability of hexaflumuron to non-target birds and mammals through the diet from 

consumption of termites that contain hexaflumuron. Combined with details regarding the

chemical properties of hexaflumuron, its application in an enclosed bait station, and further 

characterization of the consumption of subterranean termites by non-target mammals and birds, 

the potential is low for hexaflumuron to reduce survival, reproduction, and/or growth in nontarget terrestrial animals including birds, mammals, amphibians and reptiles when used in 

accordance with the current labels. EFED does not expect the current use of hexaflumuron as an 

enclosed termiticide bait to contribute to ecological risk in aquatic or terrestrial ecosystems. 

2. Problem Formulation

The purpose of Problem Formulation is to provide the foundation for the environmental fate and 

ecological risk assessment being conducted for the labeled uses of hexaflumuron. The Problem 

Formulation sets the objectives for the risk assessment and provides a plan for analyzing the data 

and characterizing the risk (USEPA 1998a). 

A preliminary Problem Formulation for the Registration Review of hexaflumuron was originally 

completed by EFED on August 12, 2009. The preliminary Problem Formulation was posted to 

the public docket (EPA-HQ-OPP-2009-0568-0003; http://www.regulations.gov/search/Regs/

home.html#documentDetail?R=0900006480a234dc) for public comment on September 23, 

20094

. The comments received were all from the technical registrant, Dow Agrosciences (DAS) 

LLC (EPA-HQ-2009-0568-0010.1; http://www.regulations.gov/search/Regs/home.html#

documentDetail?R=0900006480a5b987). In response to comments, EFED made revisions to the 

pesticide usage and effects sections of the Problem Formulation; these revisions are captured 

within the revised Problem Formulation5

 and used in this preliminary risk assessment. 

2.1. 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).

2.2. Stressor Source and Distribution

2.2.1. Nature of the Chemical Stressor

Hexaflumuron, 1-(3,5-dichloro-4-(1,1,2,2-tetrafluoroethoxy)phenyl)-3-(2,6-difluoro-benzoyl) 

urea, is an insecticide used to control termites. Hexaflumuron is a chitin synthesis inhibitor, 

which disrupts the molting process of various insects, resulting in death of immature stages when 

they molt. The mode of action is slow and allows a large number of worker termites to feed on 

 

4 US EPA, 2009.

5 US EPA, 2010.
-Page 6 of 36- 

the bait. A decline in the number of workers is followed by the demise of the colony after about 

41-45 days (MRID 455167-24), as there are insufficient workers to support dependent castes 

(MRID 455167-25). The chemical profile of hexaflumuron is provided in Table 2.1. 

Table 2.1. Chemical Profile of Hexaflumuron. 

Common name Hexaflumuron

IUPAC name 1-(3,5-dichloro-4-(1,1,2,2-tetrafluoroethoxy)phenyl)-3-(2,6-difluorobenzoyl) urea

CAS name 1-(3,5-dichloro-4-(1,1,2,2-tetrafluoroethoxy)phenyl)-3-(2,6-difluorobenzoyl) urea

Structure

Pesticide type Termiticide

Chemical class Benzoylphenylurea

CAS number 86479-06-3

Empirical formula C16H8Cl2F6N2O3

Molecular mass 461 g/mol

 2.2.2. Overview of Pesticide Usage

Hexaflumuron was originally registered for use in the United States in March 1994, through the 

Office of Pesticide Programs’ (OPP) Conventional Reduced Risk Program6. Hexaflumuron is 

used in conjunction with a monitoring system to control outbreaks of termites after a termite 

problem has been identified. Currently, hexaflumuron is registered for use in above- and belowground termite bait stations. There are three active registered products containing hexaflumuron 

(Recruit® AG, Registration Number 62719-270, Shatter®, Registration Number 62719-272, and 

Chemsico Insecticide Bait SR, Registration Number 9688-299). 

In the Recruit® AG system, the bait station is a rectangular, rigid plastic housing containing 100-

105 grams of the bait matrix (500-525 milligrams of hexaflumuron). The bait matrix is cellulose 

compressed into dry oblong "briquettes", roughly 5/8-inch long by 3/16-inch diameter, and 

contained in a sealed plastic bag. After installation (in an above-ground spot accessible to 

termites), if the bait matrix appears to be at least 1/3 to 1/2 consumed, a supplemental bait station 

can be stacked on top of the existing station. The bait station can be installed around buildings 

where food is handled, e.g., restaurants, grocery stores, bakeries, bottling plants, canneries, meat 

and poultry processing plants and grain mills. Treatment sites may include non-food handling 

areas as well, such as above-ground interior and exterior surfaces of buildings and crawl spaces, 

fences, utility poles, decking, landscape decorations, trees, and other features which could be 

damaged by termite foraging and feeding activity.

Based on manufacturer instructions, in the Shatter® system, sturdy plastic tubes (termite stations) 

are put into the ground at various intervals and around susceptible wood structures so that the top 

 

6 Information about OPP’s Reduced Risk Program: http://www.epa.gov/opprd001/workplan/reducedrisk.html
-Page 7 of 36- 

plate rests on the soil surface. Upon initial insertion of the termite stations into the ground, 

wooden “monitoring” devices (untreated with pesticide) are placed in the termite stations. The 

wooden monitoring devices are two pieces of wood coupled with an extractor (used to pull the 

monitoring devices out of the termite stations). After termite feeding has been observed on the 

untreated wooden monitoring device, the cap of the hard plastic termite station is removed and 

the wooden monitoring devices are replaced with a Shatter bait cartridge containing 50 to 55 g of 

the cellulose-based bait matrix containing 0.5% hexaflumuron (250-275 mg hexaflumuron per 

bait cartridge). The bait matrix is the same formulation as that used in the above-ground system. 

Each Shatter bait cartridge is encased in plastic shrink-wrap packaging that protects the bait 

matrix during preparation for use of the bait. At the time of installation of the bait cartridge, the 

label directs users to add up to 80 mL of “sugar-containing solution such as a sports performance 

drink” to the bait cartridge and allow it to soak into the cellulose-based bait matrix briquettes. 

According to the registrant, the sugar-containing solution is used to wet the bait and impart 

enhanced nutritional value to the bait for termites. The sugar solution acts as a short-lived 

phagostimulant, which increases the amount of bait consumed by termites per unit of time. Once 

all the liquid has been absorbed, the cap is replaced onto the bait cartridge, the plastic shrinkwrap is removed, and the bait cartridge is placed into the in-ground termite station with the top 

cap of the termite station locked into place. To maintain the integrity of the bait matrix and to 

prevent potential contamination of the bait cartridges with other substances present on the hands 

of applicators (which may deter the termites from feeding), installers may choose to wear gloves 

during the preparation of the bait cartridge. Once the termite population is suppressed or 

eradicated and no further feeding is observed, the bait cartridge is removed and disposed of by 

wrapping in paper and placing in a trash can. 

The Chemsico® Insecticide Bait SR product is similar to the Shatter® system, but can be 

installed by homeowners. Sturdy plastic tubes containing termite bait stakes (0.5% 

hexaflumuron) and locator shields are put into the ground at various intervals around susceptible 

wood structures so that the top plate rests on the soil surface. A pop-up indicator notifies the 

homeowner when termite activity has occurred at a stake. Active stakes showing evidence of 

termite activity should be replaced if 50% or more of the bait has been eaten. Used stakes are 

disposed of by wrapping in paper and placing in a trash can. All stakes must be replaced or 

removed every 12 months. 

Hexaflumuron comprises 0.5% (w/w) of all three products (approximately 0.5 g a.i. per 100 g of 

product). The current labels for hexaflumuron do not specify the maximum number of termite 

and bait stations that can be present on a designated area of land. The maximum number of inground termite stations in a given area is determined by the perimeter linear feet of the structure 

being attacked by termites. Per the label, termite stations are placed in the ground around the 

perimeter of the structure at intervals no greater than every 20 feet. Given the current wording of 

the labels, maximum potential application rates of hexaflumuron on an areal basis (i.e., lbs 

a.i./A) cannot be defined. However, as the current conceptual model for hexaflumuron exposure 

to ecological entities is different than most agricultural pesticide applications, EFED has 

determined it is not necessary to have a maximum application rate for hexaflumuron on an areal 

basis specified on the labels. Risks to non-target organisms have been calculated using 

conservative assumptions regarding the amount of hexaflumuron potentially available as bait 

matrix. 
-Page 8 of 36- 

2.3. Receptors

2.3.1. Aquatic and Terrestrial Effects

In risk assessment terminology, a “receptor” is a biological entity that is exposed to the stressor 

of interest (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 

hexaflumuron. Toxicological data generated from surrogate test species, which are intended to 

be representative of broad taxonomic groups, are used to extrapolate potential effects on a 

variety of species (receptors) included under these taxonomic groupings. 

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

available open literature are used to evaluate potential direct and indirect effects of hexaflumuron 

to aquatic and terrestrial receptors in this risk assessment. This includes toxicity on the technical 

grade active ingredient, degradates, and when available, formulated products (e.g., through use 

of “Six-Pack” studies7

). The open literature studies are identified through EPA’s 

ECOTOXicology (ECOTOX) database (USEPA 2007d, http://cfpub.epa.gov/ecotox/), which 

employs a literature search engine for locating chemical toxicity data for aquatic life, terrestrial 

plants, and wildlife. The evaluation of data may also provide insight into the direct and indirect 

effects of hexaflumuron on biotic communities from loss of species that are sensitive to the 

chemical, and from potential impacts on structural and/or functional characteristics of affected 

biological communities. 

Table 2.2 provides examples of taxonomic groups and the surrogate species tested to evaluate 

the potential ecological effects of pesticides to these non-target taxonomic groups and a 

summary of the acute toxicity classification for each taxon. 

Table 2.2. Taxonomic Groups and Test Species Evaluated for Assessing Potential Ecological Effects of 

Hexaflumuron. 

Taxonomic Group Example(s) of Surrogate Species Acute Toxicity 

Classification

Birds1 Mallard duck (Anas platyrhynchos)

Bobwhite quail (Colinus virginianus)

Practically non-toxic to 

slightly toxic

Mammals Laboratory rat (Rattus norvegicus) Practically non-toxic

Insects Honey bee (Apis mellifera L.) Practically non-toxic

3

Freshwater fish2 Bluegill sunfish (Lepomis macrochirus)

Rainbow trout (Oncorhynchus mykiss) Highly toxic

Freshwater 

invertebrates Waterflea (Daphnia magna) Very highly toxic

Estuarine/marine fish Sheepshead minnow (Cyprinodon variegatus) Not classified

Estuarine/marine 

invertebrates

Mysid (Americamysis bahia)

Eastern oyster (Crassostrea virginica) Not classified

Terrestrial plants Monocots – onion (Allium cepa) Not classified

 

7 A series of six guideline acute toxicity studies, submitted as an early step in the registration process for a pesticide. 

The acute toxicity six-pack includes: Guidelines 870.1100 Acute Oral; 870.1200 Acute Dermal; 870.1300 Acute 

Inhalation; 870.2400 Acute Eye Irritation; 870.2500 Acute Dermal Irritation; and 870.2600 Dermal Sensitization. 
-Page 9 of 36- 

Taxonomic Group Example(s) of Surrogate Species Acute Toxicity 

Classification

Dicots – carrot (Daucus carota)

Aquatic plants and 

algae

Duckweed (Lemna gibba)

Freshwater (Pseudokirchneriella subcaptata) Not classified

1 Birds represent surrogates for terrestrial-phase amphibians and reptiles. 2 Freshwater fish may be surrogates for aquatic-phase amphibians. 3

The formulated product (Consult® 100 SC, not registered in the United States) is categorized as moderately toxic to 

adult honeybees. The TGAI is classified as practically non-toxic to adult bees, indicating that the formulated product is 

more toxic than TGAI to adult honeybees.

2.3.2. Ecosystems Potentially at Risk 

Ecosystems at potential risk are often extensive in scope; therefore, it is not possible to identify 

specific ecosystems in a screening level assessment. Terrestrial ecosystems potentially at risk 

could include those in which bait stations containing hexaflumuron are placed, and areas where 

exposed termite colonies are located. 

Given the chemical properties of hexaflumuron (i.e., low vapor pressure, low solubility, high 

organic carbon normalized soil partition coefficient) and its sole application method (i.e., 

enclosed bait station), EFED assumes that spray drift of the chemical will not occur, and that 

movement of hexaflumuron via runoff and long-range atmospheric transport have a low 

likelihood of contributing to ecological risk in aquatic ecosystems. 

2.4. Assessment Endpoints 

Assessment endpoints represent the actual environmental value that is to be protected, defined by 

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

(USEPA 1998). For hexaflumuron, the ecological entities include the following: non-target

terrestrial birds, mammals, and non-target insects. The attributes for each of these entities 

include growth, survival, and reproduction (see Table 2.3 in Section 2.6.3, the Integration of 

Exposure and Effects, for further discussion). 

The assessment endpoints are intended to reflect population sustainability and community 

structure within ecosystems, and thus elucidate ecosystems that may be at risk. If risks are 

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

expected at higher levels of biological organization as well.

2.5. Conceptual Model

For a pesticide to pose an ecological risk, it must reach ecological receptors in biologically 

significant quantities. An exposure pathway is the means by which a pesticide moves in the 

environment from a source to an ecological receptor. For an ecological pathway to be complete, 

it must have a source, a release mechanism, an environmental transport medium, a point of 

exposure for ecological receptors, and a feasible route of exposure. The conceptual model is 

intended to provide a written description and visual representation of the predicted relationships 

between hexaflumuron, potential routes of exposure, and the predicted effects for the assessment 
-Page 10 of 36- 

endpoint. The conceptual model consists of two major components: the risk hypotheses and a 

conceptual diagram (USEPA 1998). 

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

uses of hexaflumuron 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 hexaflumuron as a termiticide, potential risk to non-target terrestrial birds and mammals that 

consume termites is possible (Figure 2.1). Also, in this assessment, it is assumed that the plastic 

bait station limits the availability of hexaflumuron to non-target terrestrial invertebrates as well 

as birds and mammals. The entrances to the bait stations have been configured to be large 

enough (2.5 mm) to allow termites to enter while being small enough to prevent entry by most 

native ground-dwelling bees and other terrestrial invertebrates. While EFED recognizes there 

are some species of terrestrial invertebrates small enough to enter the bait stations, other factors, 

such as foraging habits (i.e., use of cellulose materials as food) and the placement locations of 

the bait station (i.e., residential and urbanized areas), would reduce the likelihood that non-target 

terrestrial invertebrates would come into contact with hexaflumuron. Also, EFED has 

recommended that labels be amended to remove the statement directing users to add sports drink 

to the bait in order to reduce the likelihood that non-target terrestrial invertebrates become 

exposed to hexaflumuron.8

 

2.5.1. Risk Hypothesis 

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

assessment:

Based on the application method, mode of action, fate and transport, and the sensitivity 

of non-target terrestrial species, hexaflumuron has the potential to reduce survival, 

reproduction, and/or growth in non-target terrestrial animals including birds, mammals, 

amphibians and reptiles when used in accordance with the current label. These nontarget organisms include listed species as well as non-listed species. 

 

2.5.2. Conceptual Diagram 

Given the specificity of the use pattern for hexaflumuron, the transport mechanism of interest is 

the transport of hexaflumuron by termites (the target pest). The transport mechanism (i.e., 

source) is depicted in the conceptual model below (Figure 2.1) along with the receptors of 

concern and the potential attribute changes in the receptors due to exposures of hexaflumuron. 

Given the application method of hexaflumuron (i.e., bait station) and its chemical properties, it is 

assumed that spray drift of the chemical will not occur, and that movement of hexaflumuron via 

runoff and long-range atmospheric transport will not contribute to ecological risk in aquatic 

ecosystems. Also, as hexaflumuron is odorless and the bait is a cellulose matrix housed in a 

rigid plastic container with very small openings, it is unlikely that other insects, birds or 

mammals would be enticed to consume the bait containing hexaflumuron. 

 

8 Hexaflumuron: Updated Review of Waiver Request for Pollinator Field Testing (OCSPP Guideline 850.3040).

D398118. 3/22/12.
-Page 11 of 36- 

Figure 2.1. Conceptual Model Depicting Potential Risks to Non-target Species From the Use of 

Hexaflumuron. (Solid arrows depict the most likely routes of exposure and effects; dashed lines depict potential 

routes of exposure that are not considered likely.)

2.6. Analysis Plan 

2.6.1. Measures of Exposure 

2.6.1.1. Measures of Aquatic Exposure 

Given the application method of hexaflumuron (i.e., bait station) and its chemical properties, it is 

assumed that movement of hexaflumuron via runoff and long-range atmospheric transport have a 

low likelihood of contributing to ecological risk in aquatic ecosystems resulting in risk to aquatic 

vertebrates, invertebrates, and plants. Therefore, aquatic exposure modeling has not been 

conducted for hexaflumuron. 

2.6.1.2. Measures of Terrestrial Exposure

Considering the fate parameters (e.g., water solubility and slight mobility) for hexaflumuron and 

the method of application (i.e., bait stations), the only perceived means of hexaflumuron moving 

Stressor

Source

Receptors

Attribute

Change

Hexaflumuron in bait station

Direct

application Movement via 

termites

Birds / Terrestrialphase amphibians 

/ reptiles / 

mammals

Terrestrial 

Insects*

Individual organisms

Reduced survival

Reduced growth

Reduced reproduction

Food chain

Reduction in prey

Habitat integrity

Reduction in primary productivity

Reduced cover

Community change

Terrestrial/riparian plants

grasses/forbs, fruit, seeds 

(trees, shrubs)

Runoff

Mammals

Exposure

Media

Soil

Ingestion

Ingestion

Ingestion

Ingestion

Dermal uptake/Ingestion

Spray drift and 

Long range 

atmospheric 

transport

Root uptake

Wet/dry deposition

Birds / 

Amphibians

Ingestion

*Including termites
-Page 12 of 36- 

into the environment (e.g., soil and surface water) would be via termites consuming the bait and 

thereby transporting it away from the bait station to nests. Once inside the termite, 

hexaflumuron could be transferred to termite predators (animals that consume termites). Based 

on the octanol-water partition coefficient (Kow = 2.9x105) and the organic carbon partition 

coefficient (Koc range: 6,092 – 7,272 L/kgoc) of this chemical, it has the potential to 

bioaccumulate in termite predators. Therefore, this ecological risk assessment assesses 

exposures of terrestrial animals to hexaflumuron through consumption of contaminated termites

by estimating the quantity (mass) of hexaflumuron per termite and deriving dietary-based and 

dose-based exposure concentrations for terrestrial animals through consumption of contaminated 

termites. However, it is assumed that the plastic bait station limits the availability of 

hexaflumuron to non-target terrestrial invertebrates due to the size of the bait station openings, 

which have been configured to be large enough (2.5 mm) to allow termites to enter, but are small 

enough to prevent entry by most native ground-dwelling bees and other terrestrial invertebrates.9

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 2.2). The test species are not 

intended to be representative of the most sensitive species 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 ECOTOXicology database (ECOTOX), was searched in November 2013 to 

provide more ecological effects data for hexaflumuron; however, no additional data were 

available (USEPA 2013).

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

LC50 (Lethal Concentration), and EC50 (Effects 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, birds, mammals, and bees. The endpoints used for risk 

characterization 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). 

 2.6.3. Integration of Exposure and Effects 

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

ecological effects from the use of hexaflumuron in termite bait systems and the likelihood of 

direct and indirect effects to non-target organisms in terrestrial habitats. For the risk assessment 

of hexaflumuron, the risk quotient (RQ) method is used to compare estimated exposure and 

measured toxicity values. The RQ method involves dividing estimated environmental 

 

9

Hexaflumuron: Updated Review of Waiver Request for Pollinator Field Testing (OCSPP Guideline 850.3040).

D398118. 3/22/12.
-Page 13 of 36- 

concentrations (EECs) by acute and chronic toxicity values. The resulting RQs are then 

compared to the Agency’s Levels of Concern (LOC) (USEPA, 2004) (Table 2.3). These criteria 

are used to indicate when hexaflumuron’s uses, as directed on the label, result in exposure levels 

that may have the potential to cause adverse effects to non-target organisms.

Table 2.3. Agency Risk Quotient (RQ) Metrics and Levels of Concern (LOC) Per Risk Class.

Risk Class Risk Description RQ LOC

Terrestrial Animals (mammals and birds)

Acute Potential for effects to non-listed animals from acute 

exposures

EEC/LC50 (Dietary) 0.5

EEC/LD50 (Dose)

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 

3. Analysis

3.1 Use Characterization

Hexaflumuron is used in conjunction with a monitoring system to control outbreaks after a 

termite problem has been identified. Currently, hexaflumuron is registered for use in above- and 

below-ground termite bait stations. There are three active Section 3 products containing 

hexaflumuron (Recruit® AG, Registration Number 62719-270, Shatter®, Registration Number 

62719-272, and Chemsico Insecticide Bait SR, Registration Number 9688-299). Detailed 

descriptions of these products are provided in Section 2.2.2. 

Discussions with the registrant indicate that peak usage of hexaflumuron occurred in 2003, with

approximately 1,455 lbs of hexaflumuron used nationally (across the entire U.S.) by pesticide 

control operators10. Based on comments received from the registrant during the public comment 

period (EPA-HQ-2009-0568-0010.1; http://www.regulations.gov/search/Regs/home.html#documentDetail?R=0900006480a5b987), the following amounts of hexaflumuron were used 

nationwide from 2005 to 2009: 2005 - 0.14 pounds, 2006 - 3.1 pounds, 2007 - 6.49 pounds, 2008 

- 4.53 pounds, and 2009 - 3.05 pounds. In the state of California, a total of 5.3 lbs of 

hexaflumuron were applied in 2004, with total uses below 0.2 lbs applied per year from 2005 to 

2011, according to a search of the California Department of Pesticide Regulation’s Pesticide Use 

Reporting Database (http://www.cdpr.ca.gov/docs/pur/purmain.htm). 

 

10 Email communication from R. Jones to M. Clock-Rust, 3/6/2014.
-Page 14 of 36- 

3.2. Exposure Characterization

3.2.1. Environmental Fate and Transport Characterization 

The chemical and environmental fate characteristics of hexaflumuron are provided in Table 3.1

and are discussed in greater detail in the following sections. 

Table 3.1. Chemical Properties and Environmental Fate Parameters of Hexflumuron. 

Chemical/Fate parameter Value Source (MRID) Study 

Classification

Molecular Weight (g/mol) 461 NA NA

Vapor Pressure (torr) 4.43 x 10-11 426485-05 Acceptable

Octanol-water Partition Coefficient 

(Kow)

2.90 x 105

426485-05 Acceptable

Water Solubility (mg/L; at 20°C) 0.027 426485-05 Acceptable

Hydrolysis half-lives (days) Stable, pH=5 and 7

22.5, pH=9 426485-26 Acceptable

Aerobic Soil Metabolism half-life 

(days)

110 (Castle Rising sandy loam, UK)

160 (Alconbury clay loam, UK)

200 (Catlin silt loam, US)

280 (Hanford sandy loam, US)

426959-01 Supplemental

Anaerobic Soil Metabolism halflife (days)

54 (Hanford sandy loam, US)

57 (Castle Rising sandy loam, UK)

69 (Catlin silt loam, US)

72 (Alconbury clay loam, UK)

426959-01 Supplemental

Leaching/Mobility Koc (L/kgoc) 6,092 – 7,272

(range of 2 values)

Estimated 

EPISuite v4.0 NA

NA = not applicable

The primary route of dissipation for hexaflumuron, once in the soil, will be anaerobic and 

aerobic metabolism. Hexaflumuron is stable to hydrolysis at neutral to acidic pH levels, but 

degrades with a half-life of 22.5 days at pH 9. Given the methods of application (e.g., aboveand below-ground bait stations), the material will not be subject to photodegradation when used 

as proposed. Koc estimates from the Estimation Program Interface Suite (EPISuiteTM; 

http://www.epa.gov/oppt/exposure/pubs/episuite.htm) indicate that hexaflumuron is slightly to 

hardly mobile (Kashuba, 2006). Hexaflumuron's low solubility in water (0.027 mg/L at 20°C), 

high octanol-water partition coefficient Kow=2.90x105), and predicted slight mobility in soil 

based on Koc (range: 6,092 - 7,272 L/kg) indicate that hexaflumuron will not substantially 

dissolve in moisture that may enter the bait stations, so the potential for exposure from chemical 

leached from bait stations is expected to be low. Any hexaflumuron that does leach from bait 

stations is expected to bind readily to most soils. Nevertheless as a precaution, current label 

restrictions prohibit use of the bait stations “in depressions, low areas, near ponds, streams, 

springs, other water sources, or near downspout openings when the bait or its hexaflumuron 

contents could be washed out of the bait station into water at or near the surface of the ground”. 

These restrictions should further reduce the chance for hexaflumuron residues to migrate to 
-Page 15 of 36- 

surface or ground water. Although the mobility of hexaflumuron’s degradates has not been 

determined via submitted sorption studies, it appears that the degradates, which are produced in 

small quantities, are not highly mobile when evaluated using EPISuiteTM (Appendix C). Given 

hexaflumuron’s low vapor pressure and application methods, there is a low likelihood for 

volatilization of the active ingredient. 

Hexaflumuron’s persistence in aerobic and anaerobic environments has not been adequately 

determined, as the combined aerobic and anaerobic soil metabolism study (MRID 426959-01) 

were classified as supplemental, not adequate for risk assessment purposes. Under aerobic soil 

conditions, aniline-labeled hexaflumuron degraded with a half-life of 110-260 days in U.S. and 

U.K. soils. Under anaerobic soil conditions using the same soils, aniline-labeled hexaflumuron 

degraded with a half-life of 40-72 days. Given its limited use pattern and low mobility, the 

persistence of hexaflumuron in aerobic or anaerobic environments is not expected to impact the 

risk conclusions in this assessment. 

At this time, no empirical data are available to demonstrate the bioaccumulation potential of 

hexaflumuron. Bioconcentration and bioaccumulation factors (BCFs and BAFs, respectively) 

were estimated for hexaflumuron using the Kow (based) Aquatic Bioaccumulaton Model 

(KABAM v1.0; http://www.epa.gov/oppefed1/models/water/kabam/kabam_user_guide.html). 

The estimated BCF and BAF for hexaflumuron are 20,975 and 166,712 μg/kg-ww, respectively, 

indicating that hexaflumuron has the potential to concentrate and accumulate in tissues of fish 

(Appendix C; although given the current use pattern, exposure and accumulation in fish is not 

expected to occur). Analogously, given hexaflumuron’s high log Kow value (log Kow=5.46), 

there also exists the potential for hexaflumuron to bioaccumulate in bird and mammalian tissues, 

particularly for predators on termites (as the use pattern does not preclude exposure to terrestrial 

wildlife). 

EFED identified environmental degradates for hexaflumuron in its Problem Formulation (DP 

Barcode D362300, August 2009). On a structural basis and based on output from the Ecological 

Structure-Activity Relationships (ECOSARTM) component of EPISuiteTM, these degradates were 

not similar to the parent and available toxicity data did not suggest that the degradates were of 

greater or equal toxicity to non-target organisms when compared to hexaflumuron. As such, the 

focus of this assessment is the parent, hexaflumuron, with the assumption that it does not 

degrade appreciably. 

3.2.3. Measures of Terrestrial Exposure

 

3.2.3.1. Ingestion of Termites by Birds and Mammals 

As stated earlier, as a conservative measure, this ecological risk assessment assesses exposures 

of terrestrial animals to hexaflumuron through consumption of contaminated termites by 

estimating the quantity (mass) of hexaflumuron per termite and deriving dietary-based exposure 

concentrations and dose-based exposure estimates. 

Empirical data were used to represent the mass of hexaflumuron per termite. A registrantsubmitted study (MRID 455167-25) measuring the uptake rate of 0.5% 14C-labeled 
-Page 16 of 36- 

hexaflumuron in termites reported a steady state concentration of 320 ng (radioactive 

material)/termite. In this study, steady state was reached after 9-12 days. Using a representative 

termite body weight of 3 mg (Zhou et al. 2008), the measured pesticide mass per termite was 

converted to a concentration basis of 107 mg hexaflumuron/kg termites. This value was used as 

the dietary-based EEC and used to derive dose-based EECs provided in Table 3.2 for terrestrial 

animals potentially consuming termites using allometric equations intended to estimate food 

intake rates for small-, medium- and large-sized mammals and birds (USEPA, 1993). 

Table 3.2. Terrestrial EECs as Food Residues for Terrestrial Animals that Consume Termites that Contain 

Hexaflumuron. 

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)

Insectivores

Termites 1071 121.48 69.27 31.02 101.70 70.29 16.30

Equations Used to Calculate EECs in Table 3.2

The following equations (USEPA, 1993) are used to determine the food intake for birds and mammals: 

• Avian consumption: FI = (0.648 * BW0.651) / (1 - W) 

• Mammal consumption: FI = (0.621 * BW0.564) / (1 - W) 

where:

FI = food intake in grams per day

BW = body mass of animal (avian: 20 g, 100 g, 1000 g; mammal: 15 g, 35 g, 1000 g)

W = mass fraction of water in the food (0.8 for insectivores)

To calculate the dose-based EECs for birds and mammals, the following equation is used:

• Avian/Mammal Dose Based EECs: [(D * FI) / BW]

Where

D = dose of hexaflumuron in miligrams per kilogram of termites (107 mg hexaflumuron/kg termites) 

FI = food intake in grams per day

BW = body mass of animal (avian: 20 g, 100 g, 1000 g; mammal: 15 g, 35 g, 1000 g)

3.3. Ecological Effects Characterization 

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

toxicity data for the technical grade active ingredient (TGAI). The ecotoxicity data for 

hexaflumuron and its associated products have been reported in the Preliminary Problem 

Formulation for Registration Review11. These data, in addition to the ecological effects data 

submitted subsequent to the PF, are summarized briefly in Sections 3.3.1 and 3.3.2. 

 

11 US EPA, 2009 and US EPA, 2010.
-Page 17 of 36- 

3.3.1. Aquatic Toxicity Characterization

Data are available to define the toxicity of hexaflumuron to freshwater aquatic animals on an 

acute exposure basis. For both freshwater fish species tested, the median lethal concentrations 

exceeded the highest concentrations tested, which were at the solubility limit of the test material 

and indicating that the toxicity of the compound is limited by its solubility in water. 

Hexaflumuron is classified highly toxic to freshwater fish and very highly toxic to freshwater

invertebrates (Table 3.3). No data are available defining the toxicity of hexaflumuron to 

freshwater aquatic animals on a chronic exposure basis. In addition, no data are available to 

describe the toxicity of hexaflumuron to marine/estuarine animals or aquatic plants.

Table 3.3. Summary of Most Sensitive Endpoints from Submitted Aquatic Toxicity Studies for 

Hexaflumuron.

Species

(common name)

Taxa 

Represented

EndpointDuration

(hours)

Mean 

concentration 

(μg a.i./L)

Citation

MRID

Study 

Classification

Lepomis 

macrochirus

(bluegill sunfish) Freshwater 

fish and 

aquatic-phase 

amphibians

LC50 96

>255.6* 426485-11

Supplemental

Practically 

non-toxic

Onchorynchus

mykiss

(rainbow trout)

> 535.5* 426485-12

Supplemental

Practically 

non-toxic

Daphnia magna

(water flea)

Freshwater 

invertebrates LC50 48 0.111 426485-13

Acceptable

Very highly 

toxic

 *Exceeds the solubility limit (27 μg/L; MRID 426485-05).

3.3.2. Terrestrial Effects Characterization

Hexaflumuron is classified as practically non-toxic to mammals and birds on an acute oral 

exposure basis. On a subacute dietary exposure basis, hexaflumuron is classified as slightly 

toxic to birds (NOAEC=2,201 ppm; Table 3.4). In chronic bird studies with mallard ducks 

(Anas platyrhynchos) and bobwhite quail (Colinus virginianus), hexaflumuron resulted in 

reduced survival. In a developmental toxicity study with rats (Rattus norvegicus), hexaflumuron 

resulted in reduced pup body weights. In honeybees (Apis mellifera), the formulated product 

(Consult® 100 SC, not registered in the United States) was determined to have roughly 

equivalent toxicity in both acute contact and oral toxicity tests and is categorized as moderately 

toxic to honeybees. However, the TGAI is classified as practically non-toxic to bees, indicating 

that the formulated product is more toxic than TGAI to adult honeybees. Plant toxicity data are 

not required for hexaflumuron due to the contained nature of the bait station use pattern.

12

Table 3.4 contains a summary of the most sensitive terrestrial ecological effects data for 

hexaflumuron. A number of ecological effects studies on birds, mammals and honeybees (Apis 

 

12 Not required for contained pesticide treatments such as bait stationes and pheromone traps unless unless adverse 

effects reports are received by the Agency.[(40CFR 158.660 (e)(1))
-Page 18 of 36- 

mellifera) with hexaflumuron have been submitted and reviewed since the issuance of the 

Problem Formulation (2009-2010). The results of these data reviews have been summarized 

here and used to inform the risk assessment for non-target organisms from exposure to 

hexaflumuron (Table 3.4). 

A 2-generation reproduction study with the rat (Rattus norvegicus) was reviewed by the Health 

Effects Division in 2009 (MRID 442330-03). No adverse, treatment-related effects were 

observed on adult (parental) mortality, clinical signs, body weight, body weight gain, food 

consumption, hematology, organ weights, or gross or histological pathology throughout the study 

in either generation. The LOAEL for parental and reproductive toxicity were not established at 

the dietary levels tested. However, the LOAEL for offspring toxicity was observed based on 

decreased pup body weights at 125 mg/kg bw/day dose level; the NOAEL is 25 mg/kg bw/day, 

corresponding to a NOAEC of 500 mg/kg-diet. 

An avian reproduction toxicity study with mallard ducks (Anas platyrhynchos) was reviewed by 

EFED in 2012 and classified as supplemental (MRID 483232-05). The NOAEC was 29.4 mg 

ai./kg-diet (mean-measured) and the LOAEC was 96.5 mg ai./kg-diet (mean-measured) based on 

reduced survival (i.e., reduced numbers of viable embryos and hatchling survival) and reduced 

growth (i.e., hatchling body weights). Conclusions for birds were assumed to apply to terrestrialphase amphibians and reptiles given the absence of data for these two taxa. 

Acute contact and oral toxicity studies with adult honey bees have been reviewed by EFED13. 

Tests using TGAI and adult bees yielded acute contact and oral 48-hr LD50 values of >99.6 μg 

ai/bee (MRID 483232-08) indicating that the compound is practically non-toxic to adult bees on 

an acute exposure basis. In studies conducted with a formulated end-use product containing 

hexaflumuron (Consult® 100 SC; 10% hexaflumuron) the LD50 value for the acute contact 

toxicity test was 5.83 (95% confidence interval: 5.10-6.74) μg a.i./bee. The LD50 value for the 

acute oral toxicity test was equivalent to 5.68 (95% confidence interval: 4.86-6.77) μg a.i./bee. 

These data indicate that the formulated product has roughly equivalent toxicity in both acute 

contact and oral toxicity tests, and is categorized as moderately toxic to honeybees on an acute 

exposure basis. The data indicate that the formulated product (Consult® 100 SC) is more toxic 

than TGAI to adult honeybees. The formulated end use product Consult® 100 SC is not a 

registered formulation in the U.S.; therefore, there is uncertainty regarding how the results of 

these tests relate to hexaflumuron products registered in the U.S. 

Table 3.4. Summary of Most Sensitive Endpoints from Submitted Terrestrial Toxicity Studies for 

Hexaflumuron.

Species

(common name)

Taxa 

Represented End-point Mean 

Concentration

Citation

MRID

Study 

Classification, 

Acute 

Toxicity 

Classification

Rattus norvegicus

(laboratory rat)

mammals

Acute Oral

LD50

>5,000 mg/kg

bw 426485-14

Acceptable

Practically 

non-toxic

 

13 D362299. MRID 483232-07. 3/1/12.
-Page 19 of 36- 

Species

(common name)

Taxa 

Represented End-point Mean 

Concentration

Citation

MRID

Study 

Classification, 

Acute 

Toxicity 

Classification

2-Generation 

Reproduction

NOAEL

(NOAEC)

25 mg/kg/day

(500 mg/kg-diet)

442330-03 Acceptable

Anas platyrhynchos

(mallard duck)

birds, 

terrestrial-phase 

amphibians and 

reptiles

Acute Oral

LD50

>2,000 mg/kg

bw 426485-08

Acceptable

Practically 

non-toxic

Avian 

Reproduction

NOAEC

29.4 mg a.i./kgdiet 483232-05 Supplemental

Colinus virginianus

(northern bobwhite 

quail)

birds, 

terrestrial-phase 

amphibians and 

reptiles

Subacute 

Dietary

LC50

2,201 ppm 426485-09 Acceptable

Slightly toxic

Apis mellifera 

(Honeybee)

Terrestrial 

invertebrates

Contact LD50 >99.6 μg a.i./bee

483232-08

Acceptable

Practically 

Oral LD non-toxic 50 >99.6 μg a.i./bee

TEP Contact 

LD50

5.83 μg a.i./bee

483232-07

Supplemental

Moderately 

toxic TEP Oral 

LD50

5.68 μg a.i./bee

3.3.3. Review of Incident Data 

A preliminary review of the Ecological Incident Information System (EIIS) maintained by the 

Agency’s Office of Pesticide Programs (OPP) indicates that there are no reported ecological 

incidents associated with the use of hexaflumuron (November, 2013). The absence of reported 

incidents can not be construed as the absence of incidents. Incident reports for non-target 

animals typically provide information on mortality events only. Reports for other adverse 

effects, such as reduced growth or impaired reproduction, are rarely received. EPA’s changes in 

the registrant reporting requirements of incidents may also account for the reduced number of 

reported incidents even for mortality events. 

The American Bird Conservancy (ABC) Avian Incident Monitoring System (AIMS) was 

searched on November 14, 2013 and returned no records of incidents associated with 

hexaflumuron (ABC, 2013).

A report from the National Pesticide Information Centers (NPIC) at Oregon State University 

summarizes incident reports received between April 1, 1995 and December 31, 2013. Ten
-Page 20 of 36- 

reports mentioned hexaflumuron. The certainty index of the reports ranged from ‘unlikely’ to 

‘possible’. None of the reports mentioned wildlife. About half of the reports were for pet dogs 

that had accidentally consumed a bait station containing hexaflumuron after it had been installed 

in the ground surrounding residential buildings; however, these reports were not considered to be 

definitively caused by hexaflumuron due to a lack of information (e.g., NPIC assigned a 

certainty index of either unclassifiable or unlikely). The remainder of the reports concerned 

individuals that had accidentally ingested or believed they had become exposed to hexaflumuron 

through misuse/non-registered uses. 

4. Risk Characterization

4.1. Risk Estimation 

This screening-level assessment of the labeled uses of hexaflumuron 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, as shown in Table 4.1. 

Inputs used to derive these results are provided in Appendix A, while the results of the 

calculations are provided in Appendix B. The LOCs 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 nontarget organisms. For listed species, LOC exceedances require an additional in-depth listed 

species evaluation of the potential co-occurrence of listed species and areas in which 

hexaflumuron is used to characterize risks.

As acute mammalian and avian toxicity endpoints are non-definitive (‘greater than’ values; see 

Table 3.4), RQs were not estimated. However, a characterization of acute risks to mammals and 

birds is provided in Section 4.2. 

Acute avian dietary-based RQ values for birds are based on the subacute dietary LC50 of 2,201 

ppm for the bobwhite quail and are below the acute risk levels of concern for both listed and 

non-listed species. 

Chronic dietary-based risk to birds is estimated by comparing dietary EECs to the avian NOAEC 

based on reduced hatchling survival (29.4 mg a.i./kg-diet), and the resultant RQ value (3.63) 

exceeds the chronic risk LOC (1.0). For this RQ estimate, small birds are assumed to consume 

roughly 1/3 of their diet as termites containing hexaflumuron (2,113 termites/day) to result in 

reproductive toxicity to birds. 

Chronic dose-based risks are not calculated for birds as a chronic dose-based endpoint is not 

available (the dietary-based avian NOAEC was used to estimate chronic risks).

For mammals, chronic risk is calculated on a dietary basis and on a per-dose basis. Dietarybased risks for mammals resulted in an RQ of 0.21 which does not exceed the LOC (1) for 

chronic mammal risk. The chronic dose-based RQ values are estimated using an adjusted 
-Page 21 of 36- 

NOAEL for mammals based on the of 25 mg a.i./kg bw/day (see Appendix A). Dose-based 

chronic risk estimates exceed the chronic risk LOC of 1.0 for small (15 g) and medium (35 g) 

sized mammals (RQ=1.85 for small mammals; 1.58 for medium mammals). For this RQ 

estimate, small and medium mammals are assumed to consume roughly 55% and 63% of their 

diet as termites containing hexaflumuron to result in a LOC exceedance. For a detailed 

description of these risk calculations, see Appendix D. 

 

Table 4.1. Acute and Chronic RQs for Birds and Mammals of Different Feeding Classes.

BIRDS

Food 

Type

Acute

Dietary Based

RQs

Acute

Dose Based

(mg/kg-bw)

Chronic

Dietary 

Based

RQs

Chronic

Dose Based

(mg/kg-bw)

All Size 

Classes

Small

(20 g)

Medium

(100 g)

Large

(1000 g)

All Size 

Classes

Small

(20 g)

Medium

(100 g)

Large

(1000 g)

Herbivores/Insectivores

Termite N/A N/A N/A N/A 3.63 N/A N/A N/A

MAMMALS

Food 

Type

Acute

Dietary Based

RQs

Acute

Dose Based

(mg/kg-bw)

Chronic

Dietary 

Based

RQs

Chronic

Dose Based

(mg/kg-bw)

All Size 

Classes

Small

(15 g)

All Size 

Classes

Large

(1000 g)

All Size 

Classes

Small

(15 g)

Medium

(35 g)

Large

(1000 g)

Herbivores/Insectivores

Termite N/A N/A N/A N/A 0.21 1.85 1.58 0.85

Dietary-based chronic RQ values are based on the bobwhite quail NOAEC value of 29.4 mg/kg diet (LOAEC = 180 

mg/kg diet) and for mammals the NOAEC of 500 mg/kg diet. 

Bold values indicate that the RQ exceeds the LOC for acute risk (LOC = 0.5, nonlisted, LOC = 0.1, listed species) 

or chronic risk to listed and nonlisted birds or mammals (LOC = 1).

4.2. Risk Description

Acute mammalian and avian dose-based risks are quantitatively estimated using T-REX, but it 

should be noted that acute avian and mammal endpoints are non-definitive (‘greater than’ values; 

see Table 3.4). When the non-definitive endpoints are used in a risk estimation for mammals, 

the mammalian acute dose-based RQ values (based on the nondefinitive Norway rat acute oral 

LD50 of >5,000 mg a.i./kg bw) did not exceed the acute risk LOC for listed (LOC = 0.1) or nonlisted (LOC = 0.5) mammals. For birds, if the non-definitive endpoint (LD50>2,000 mg a.i./kg 

bw) is used to estimate acute risk, the calculated avian acute dose-based RQ value (0.12) exceeds 

the LOC for listed (LOC=0.1) small (20 g) birds. However, as the adjusted LD50 for small birds 

is 1,038 mg a.i./kg-bw (equivalent to an internal dose in a 20-g bird of 20.76 mg a.i.), this is 

roughly equivalent to a small bird ingesting 64,875 termites (containing a steady state of 320 ng 

hexaflumuron/termite). Assuming each termite weighs 3 mg, the equivalent weight of the 

termites (195 g) is more than 8 times what a small bird would be expected to eat in a day14. For a 

 

14 USEPA. 1993. Wildlife exposure factors handbook. Volume I of II. EPA/600/R-93/187a. Office of Research and 

Development, Washington, D.C. 20460.
-Page 22 of 36- 

detailed description of these risk calculations, see Appendix D. The likelihood of acute adverse 

effects in small birds from ingestion of termites containing hexaflumuron residues is considered 

to be low. 

Chronic dietary-based risk to birds is estimated by comparing dietary EECs to the avian NOAEC 

based on reduced hatchling survival (29.4 mg a.i./kg-diet), and the RQ value (3.63) exceeds the 

chronic risk LOC (1.0). For this RQ estimate, small birds are assumed to consume 

approximately 30% of their diet as termites containing hexaflumuron (see Appendix D for 

calculations). Bearing in mind that the NOAEC is the dose at which no adverse effects were 

observed and that the risk estimate assumes a significant, continuous level of dietary exposure to 

birds from hexaflumuron through termites that contain hexaflumuron, EFED believes the 

likelihood of chronic adverse effects to birds is low. 

For mammals, the chronic risk estimates exceed the chronic risk LOC of 1.0 for small (15 g) and 

medium (35 g) sized mammals based on dietary exposure through consumption of termites that 

contain hexaflumuron. However, these risk estimates are based on the assumption that small 

mammals consume 7.7 g termites per day or about 55% of the daily food intake as termites 

(medium mammals are assumed to consume 63% of the daily food intake as termites; see 

Appendix D for calculations).

Chronic risk estimates for mammals can be further characterized by considering the LOAEL of 

125 mg a.i./kg-bw/day at which the adverse effects were observed (reduced pup body weights). 

The LOAEL is higher than the EECs for small and medium mammals (70.3 mg a.i./kg-bw/day 

and 101.7 mg a.i./kg-bw/day, for medium and small mammals, respectively). The EECs are 

below the LOAEL at which effects were observed, reducing the likelihood that mammals would 

consume enough termites containing hexaflumuron to result in adverse effects. Given the 

conservative assumptions, the likelihood of adverse effects from chronic exposure to 

hexaflumuron residues in termites is considered low based on comparison to the LOAEL. 

Consequently, EFED believes the likelihood of chronic adverse effects to mammals from the 

labeled use of hexaflumuron is low.

Aside from the risk estimates that are based on conservative assumptions, the registered use 

pattern (bait stations) makes exposure to wildlife unlikely, as hexaflumuron is used in residential 

and semi-residential settings for structural pest control. Further, data on termites and non-target 

terrestrial animals that may feed upon them, including the amount and rate of consumption, can 

be used to inform the risk characterization for hexaflumuron. 

There are a variety of bird and mammal species for which termites can be a major, regular 

constituent of their diet. The vast majority of these occur outside the US (chimps, anteaters, 

aardwolf, some birds, etc.). The major exception is the nine banded armadillo (Dasypus 

novemcinctus). This species does occur within the US

(http://www.mnh.si.edu/mna//image_info.cfm?species_id=58) and termites can be a regular part 

of their diet, although a secondary food item (ants and termites together ~14% of diet, Davis and 

 
-Page 23 of 36- 

Schmidly 199715). It should be noted that the nine banded armadillo is not a federally designated 

endangered or threatened species.

Subterranean termites, which these baits are intended for use against, are not considered an 

accessible prey item. They live underground, in mud tubes or in wood. As each worker only 

weighs 2-3 mg, with queens weighing less than 7 mg at colony foundation (Long 200516), the 

caloric benefit to locating and consuming subterranean termites is minimal. The exception 

would be during spring mating flights, when alates (winged, reproductive termites) swarm. 

During this time the swarming termites contain a substantial amount of fat and are considered a 

food item for many organisms: ants, birds, bats, various mammals (mice to bears), fish, reptiles, 

and other opportunistic insectivores (Nutting, 196917). These swarms are exclusively localized, 

ephemeral sources of food and would not contain hexaflumuron, as the swarm would not be 

composed of exposed worker termites. As such, exposure to hexaflumuron would not be 

expected. 

For terrestrial invertebrates, toxicity data are available for adult bees. Toxicity data are not 

available for larval bees, which would be expected to be susceptible to hexaflumuron based on 

the mode of action (molting inhibition). However, given that the chemical is enclosed in an 

underground bait station, exposure to larval bees is unlikely. Also, there appears to be a 

discrepancy between the toxicity of the TGAI and the formulated product based on acute oral 

and contact toxicity studies with honey bees, where the formulated product (Consult 100 SC, 

10% a.i.) is moderately toxic, while the TGAI is practically non-toxic. This formulated product 

is not used in the United States. While EFED recognizes there are some species of terrestrial 

invertebrates small enough to enter the bait stations, other factors, such as foraging habits (i.e., 

use of cellulose materials as food) and the placement locations of the bait station station (i.e., 

residential and urbanized areas), would reduce the likelihood that non-target terrestrial 

invertebrates would come into contact with hexaflumuron. Therefore, the exposure and risk to 

non-target terrestrial invertebrates is expected to be low. 

Finally, the following considerations were also used to further support EFED’s risk conclusions

of minimal risk18: 

1.) Not all of the bait material is available over the entire exposure period. The baits are 

designed to contain enough material to last at least 6 months under the heaviest foraging 

conditions. Some of the baits last a year. The amount of hexaflumuron circulating 

within the colony at any single time is a fraction of the total consumed over the entire 

baiting period. 

 

15 Davis W.B. and D.J. Schmidly. 1997. The Mammals of Texas - Online Edition. Texas Tech University. Available 

online. http://www.nsrl.ttu.edu/tmot1/.

16 Long. CE 2005. Reticulitermes flavipes (Isoptera: Rhinotermitidae) colonies: reproductive lifespans, caste ratios, 

nesting and foraging dynamics, and genetic architecture. (Doctoral dissertation). Abstract available online. 

http://www.ncbi.nlm.nih.gov/pubmed/14641982. 17 Nutting, W.L. 1969. Flight and colony foundation. In K. Krishna and F. M. Weesner (Ed.) Biology of Termites, 

vol 1 (pp. 233-282). Academic Press, New York, NY. 

18 Email correspondance with Mark Suarez, Registration Division, OPP. 1/14/14.
-Page 24 of 36- 

2.) The amount of hexaflumuron in any individual termite is likely to be less than what they 

consumed from the bait, unless they are consumed while on the bait (immediately). The 

termites do not retain all of the hexaflumuron they consume. They feed it to other 

termites, they die and their bodies decompose quickly, and/or it ends up deposited in the 

underground foraging tubes.

3.) The portion of a non-target animal’s diet that is composed of termites is not reflective of 

the amount of hexaflumuron that might be ingested. The non-target species will consume 

both “tainted and untainted” termites. Even if the termite predator only consumed 

termites and only termites from the tainted colony, the number of untainted termites for 

consumption would be much greater. 

4.) The baits are designed to kill the termites. They act slowly, but are designed to be 

efficacious on the order of months, not years. As a result, the potential for exposure is 

further reduced to the window of time between when the termites first begin foraging at 

the bait and when foraging at the bait ends. 

4.3 Risk Conclusions 

The risk hypothesis identified in the Problem Formulation stated, “[b]ased on the application 

method, mode of action, fate and transport, and the sensitivity of non-target terrestrial species, 

hexaflumuron has the potential to reduce survival, reproduction, and/or growth in non-target 

terrestrial animals including birds, mammals, amphibians and reptiles when used in accordance 

with the current label. These non-target organisms include listed species as well as non-listed 

species.” Based on the findings within this risk assessment, the hypothesis above is not 

supported, and that the potential is low for hexaflumuron to reduce survival, reproduction, and/or 

growth in non-target terrestrial animals including birds, mammals, amphibians and reptiles when 

used in accordance with the current labels. 

Hexaflumuron's low solubility in water, high octanol-water partition coefficient, and predicted 

slight mobility in soil indicate that hexaflumuron will not substantially dissolve in moisture that 

may enter bait stations, so the likelihood of exposure from runoff of chemical leached from bait 

stations is expected to be low. Any hexaflumuron that does leach from bait stations should bind 

readily to most soils. Given hexaflumuron’s low vapor pressure and application methods, the 

likelihood of volatilization of the active ingredient is expected to be low. The primary route of 

dissipation for hexaflumuron, once in the soil, will thus be decay via anaerobic and/or aerobic 

microbial metabolism. Hexaflumuron is stable to hydrolysis at neutral to acidic pH, but labile to 

hydrolysis at alkaline pH (half-life of 22.5 days at pH 9). Given the methods of application (e.g., 

above- and below-ground bait stations), hexaflumuron will not be subject to photodegradation

when used as described on product labels. Current label restrictions prohibiting the use of the 

bait stations “in depressions, low areas, near ponds, streams, springs, other water sources, or 

near downspout openings when the bait or its hexaflumuron contents could be washed out of the 

bait station into water at or near the surface of the ground”, reduce the chances for 

hexaflumuron to migrate to surface and ground water. The estimated BCF and BAF for 

hexaflumuron indicate that hexaflumuron has the potential to concentrate and accumulate in 

tissues of fish (although as noted previously, hexaflumuron is unlikely to reach the aquatic 
-Page 25 of 36- 

environment/fish), and given hexaflumuron’s high Kow value (log Kow >5) there also exists the 

potential for hexaflumuron to bioaccumulate in avian and mammalian tissues, particularly those 

of insectivores that consume termites. However, as discussed below, EFED believes that the 

likelihood of potential risk to non-target birds and mammals is low.

While hexaflumuron is highly toxic to some organisms (freshwater invertebrates), the application 

method of hexaflumuron (i.e., bait station) makes it unlikely that the termiticide will be released 

into the environment under normal use. This is especially true for the aquatic environment, 

given the prohibition of application near waterbodies and the chemical properties of 

hexaflumuron, the ability of hexaflumuron to move via runoff, spray drift and long-range 

atmospheric transport is limited. Consequently, there is a low likelihood of ecological risk posed 

to aquatic vertebrates, invertebrates, and plants by hexaflumuron. 

In the terrestrial environment, it is unlikely that hexaflumuron (which is housed in bait stations) 

will be released into the environment; however, terrestrial wildlife may be exposed by ingesting 

termites that have fed on the baits. The screening-level ecological risk assessment indicates a 

potential for chronic risk to birds and mammals (Table 4.1). However, the LOC exceedance for 

birds and mammals is based on conservative assumptions described above in Section 4.2, Risk 

Description. Based on the screening level estimates of chronic risk, combined with information 

on the use pattern (primarily residential) for hexaflumuron, as well as information on the diet and 

habits of insectivorious species of birds and mammals, EFED concludes that the potential for 

risk to non-target terrestrial organisms from the labeled uses of hexaflumuron is low. 

5. Federally Threatened and Endangered (Listed) Species of Concern

Based on this screening-level assessment, while the use of hexaflumuron “May Affect” listed 

birds, reptiles, terrestrial-phase amphibians and mammals; the EPA makes a “Not Likely to 

Adversely Affect” (NLAA) determination for these taxa based on the use pattern of 

hexaflumuron and information about the diets of insectivorious species of birds and mammals 

where the likelihood of exposure or adverse responses is considered discountable. Additionally, 

based on this screening-level assessment and the use pattern of hexaflumuron, EPA makes a “No 

Effect” determination for aquatic organisms and plants and a No Habitat Modification 

determination for all designated critical habitats based on the currently registered uses of 

hexaflumuron evaluated in this assessment. 

Table 5.1. Effects Determination for Direct and Indirect Effects of Hexaflumuron on Taxa

Assessment Endpoint Effects 

Determination

Basis for Determination

Birds, Terrestrial-phase Amphibians, Reptiles and Mammals

Direct Effects

Survival, growth and 

reproduction

NLAA

• Uses confined to residential/urban settings

• Enclosure of chemical in bait station 

constructed to limit exposure to nontarget organisms.

• Low solubility and high Koc limit mobility 

and decrease likelihood for exposure to 

non-target organism.

Low likelihood of exposure makes direct 

effects to listed animals discountable.

Indirect Effects

Survival, growth and NLAA
-Page 26 of 36- 

reproduction via effects to 

food supply

Aquatic Organisms and Aquatic Plants

Direct Effects

Survival, growth and 

reproduction

NE • Enclosure of chemical in bait station 

constructed to limit exposure to nontarget organisms.

Low solubility and high Koc limit mobility and 

decrease likelihood for exposure to non-target 

Indirect Effects organism.

Survival, growth and 

reproduction via effects to 

food supply

NE

Table 5.2. Effects Determination for Critical Habitat Impact Analysis

Designated Critical Habitat 

for:

Effects 

Determination

Basis for Determination

Birds, Terrestrial-phase 

Amphibians, Reptiles and 

Mammals

No Habitat 

Modification

• Uses confined to residential/urban settings

• Enclosure of chemical in bait station 

constructed to limit exposure to nontarget organisms.

Aquatic Organisms and 

Aquatic Plants

No Habitat 

Modification

• Uses confined to residential/urban settings

• Enclosure of chemical in bait station 

constructed to limit exposure to nontarget organisms.

6. Endocrine Disruptor Screening Program 

As required by FIFRA and 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 reproductive effects in different 

taxonomic groups. As part of its most recent registration decision for hexaflumuron, 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), 

hexaflumuron 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 
-Page 27 of 36- 

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, 201319 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. 

7. References

CFR 40. 2007. Code of Federal Regulations 40 Parts 150 to 189. Protection of the 

Environment. U.S. Government Printing Office. 

Davis W.B. and D.J. Schmidly. 1997. The Mammals of Texas - Online Edition. Texas Tech 

University. Available online. http://www.nsrl.ttu.edu/tmot1/. 

Howard, P.H., Boethling, R.S., Stiteler, W.M., Meylan, W.M., Hueber, A.E., Beauman, J.A., and 

M.E. Larosche. 1992. Predictive model for aerobic biodegradability developed from a file of 

evaluated biodegradation data. Environ. Toxicol. Chem. 11: 593-603. 

Julin, A.M., and H.O. Sanders. 1978. Toxicity of the IGR, Diflubenzuron, to Freshwater 

Invertebrates and Fishes. Mosq.News 38(2):256-259 (Author Communication Used) (Publ in 

Part As 6797). (ECOTOX reference #939). 

Kashuba, R., Spatz, D. 2006 Memorandum to Steven Bradbury, Subject: Standard Soil Mobility 

Classification Guidance 

Long. CE 2005. Reticulitermes flavipes (Isoptera: Rhinotermitidae) colonies: reproductive 

lifespans, caste ratios, nesting and foraging dynamics, and genetic architecture. (Doctoral 

dissertation). Abstract available online. http://www.ncbi.nlm.nih.gov/pubmed/14641982 

Maciorowski, A. 1993. Ecological Effects Review of Hexaflumuron for an Experimental Use 

Permit as a Termiticide in a “Safer Pesticide” Formulation. EPA File Symbol: 62719-EUP-EL, 

Chemical: 118202, DP Barcode D192759, Action: 700, EUP NC-non-food/feed. 

Nutting, W.L. 1969. Flight and colony foundation. In K. Krishna and F. M. Weesner (Ed.) 

Biology of Termites, vol 1 (pp. 233-282). Academic Press, New York, NY 

 

19 See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list 

of chemicals.
-Page 28 of 36- 

US EPA. 1993. Wildlife Exposure factors handbook. United States Environmental Protection 

Agency. Office of Research and Development. EPA/600/R-93/187. 

US EPA. 1998. Guidelines for Ecological Risk Assessment. Risk Assessment Forum, Office of 

Research and Development, Washington, D.C. EPA/630/R-95/002F. April 1998. 

http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=30759 

US EPA. 2004. Overview of the Ecological Risk Assessment Process in the Office of Pesticide 

Programs. U.S. Environmental Protection Agency, Office of Prevention, Pesticides and Toxic 

Substances, Office of Pesticide Programs, Washington DC. January 23, 2004. 

US EPA. 2007b. Ecological Incident Information System. 

http://www.epa.gov/pesticides/science/efed/policy_guidance/team_authors/endangered_species_

reregistration_workgroup/esa_incident_guidance.htm#searching

USEPA. 2007c. 40 CFR Part 158. Pesticides; Data Requirements for Conventional Chemicals: 

Final Rule. 72 FR 60934. October 26, 2007. 

US EPA. 2007d. ECOTOXicology Database. Office of Research and Development National 

Health and Environmental Effects Research Laboratory’s (NHEERL’s) Mid-Continent Ecology 

Division (MED). http://cfpub.epa.gov/ecotox/ 

US EPA. 2009. Problem Formulation for the Environmental Fate, Ecological Risk, Endangered

Species and Drinking Water Assessments for Hexaflumuron. D362300. 8/12/2009. 

US EPA. 2010. Revised Problem Formulation for the Environmental Fate, Ecological Risk, 

Endangered Species and Drinking Water Assessments in Support of the Registration Review of

Hexaflumuron. D362322. 3/11/2010. 

U.S. Fish and Wildlife Service (USFWS) and National Marine Fisheries Service (NMFS). 1998. 

Endangered Species Consultation Handbook: Procedures for Conducting Consultation and 

Conference Activities Under Section 7 of the Endangered Species Act. Final Draft. March 

1998. 

Zhou, X., Wheeler, M.M., Oi, F.M., and M.E. Scharf. 2008. RNA interference in the termite 

Reticulitermes flavipes through ingestion of double-stranded RNA. Insect Biochemistry and 

Molecular Biology, 38 (8): 805-815. 

SUBMITTED STUDIES:

MRID: 455167-25 

Sheets, J. (1997) Uptake rate of (14C) Hexaflumuron Force-Fed to Groups of Reticulitermes 

flavipes: Report ID: DEI0376. Unpublished study prepared by Dow Agrosciences LLC. 

SUBMITTED FATE STUDIES:
-Page 29 of 36- 

MRID: 426485-05 

Jones-Jefferson, T. (1992) Series 63: Physical and Chemical Characteristics of the Technical 

Grade of Active Ingredient, Hexaflumuron (DE-473): Lab Project Number: GHC 2927: 

FOR92076: FOR92100. Unpublished study prepared by DowElanco, Leeds University (UK) and 

Huntingdon Research Centre (UK). 

MRID: 426485-26 

Jackson, R.; Yon, D. (1992) The Hydrolysis of Hexaflumuron in Buffered Distilled Water at pH 

5, 7 and 9: Lab Project Number: GHE-P-2795. Unpublished study prepared by DowElanco, 

Letcombe (UK).

MRID: 426959-01 

Racke, K. (1993) Aerobic and Anaerobic Soil Metabolism of Hexaflumuron: Lab Project 

Number: GH-C 2970. Unpublished study prepared by DowElanco North American 

Environmental Chemistry Lab. 

MRID: 426485-27 

Racke, K. (1993) Leaching and Adsorption/Desorption of Hexaflumuron: Lab Project Number: 

GH-C 2969. Unpublished study prepared by DowElanco. 

SUBMITTED EFFECTS STUDIES:

MRID: 426485-07 

Mayes, M. (1992) Acute Oral Toxicity (LD50) of XRD 473 to the Bobwhite Quail: Summary 

Evaluation and Original Study (Appendix A): Lab Project Number: DWC 510/871169. 

Unpublished study prepared by DowElanco. 

MRID: 426485-08 

Mayes, M. (1992) Acute Oral Toxicity (LD50) of XRD 473 to the Mallard Duck: Summary 

Evaluation and Original Study (Appendix A): Lab Project Number: DWC 494/86154. 

Unpublished study prepared by DowElanco. 

MRID: 426485-09 

Mayes, M. (1992) The Dietary Toxicity of XRD 473 to the Bobwhite Quail: Summary 

Evaluation and Original Study (Appendix A): Lab Project Number: DWC 511/871193. 

Unpublished study prepared by DowElanco. 

MRID: 426485-10 

Mayes, M. (1992) The Dietary Toxicity of XRD 473 to the Mallard Duck: Summary Evaluation 

and Original Study (Appendix A): Lab Project Number: DWC 512-871194. Unpublished study 

prepared by DowElanco. 
-Page 30 of 36- 

MRID: 426485-11 

Mayes, M. (1992) The Acute Toxicity of XRD 473 to Bluegill Sunfish: Summary Evaluation and 

Original Study (Appendix A): Lab Project Number: 87/DCSO32/556. Unpublished study 

prepared by DowElanco. 

MRID: 426485-12 

Mayes, M. (1992) The Acute Toxicity of XRD 473 to Rainbow Trout: Summary Evaluation and 

Original Study (Appendix A): Lab Project Number: 87/DCSO32/555. Unpublished study 

prepared by DowElanco. 

MRID: 426485-13 

Mayes, M. (1992) The Acute Toxicity of XRD 473 to Daphnia magna: Summary Evaluation and 

Original Study (Appendix A): Lab Project Number: AFT/86/009. Unpublished study prepared by 

DowElanco. 

MRID: 426485-14 

Cosse, P.; Sames, K.; Berdasco, N. (1993) DE-473: Acute Oral Toxicity Study in Fischer 344 

Rats: Lab Project Number: DR-0210-2650-004A: DR-0210-2650-004A1. Unpublished study 

prepared by Dow Chemical Co. 28 p. 

MRID: 442330-03 

Koeter, H.; van Marwijk, M.; Bruyntjes, J. (1988) Oral Multigeneration Reproduction Study with 

XRD-473 in Rats: Lab Project Number: B86-0385: DET 1165: 857. Unpublished study prepared 

by TNO-CIVO Institutes. 500 p. 

 

Appendix A: Toxicity Input Values for Risk Estimation for Hexaflumuron (HF)

termite bw 3 mg/termite

conc 320 ng HF/termite

dose 107

mg ai/kg 

termite from pg 13 of PF

LD50 2000 mg/kg-bw mallard

Adjusted LD50 Bird

20 N/A mg/kg-bw

100 N/A mg/kg-bw

1000 N/A mg/kg-bw

LC50 2201 mg/kg-diet bobwhite

NOAEC 29.4 mg/kg-diet mallard

LD50 5000 mg/kg rat

Adjusted LD50 Mammal
-Page 31 of 36- 

15 N/A mg/kg

35 N/A mg/kg

1000 N/A mg/kg

NOAEL 25 mg/kg-day NOAEC 500 mg/kg-diet

Adjusted NOAEL Mammal

15 55 mg/kg-day

35 44 mg/kg-day

1000 19 mg/kg-day
-Page 32 of 36- 

Appendix B: Risk Estimation for Hexaflumuron

Avian Body Ingestion (Fdry) Ingestion (Fwet) % body wgt FI

Class Weight (g) (g bw/day) (g/day) consumed (kg-diet/day)

Small 20 5 23 114 2.28E-02

Mid 100 13 65 65 6.49E-02

Large 1000 58 291 29 2.91E-01

Mammalian Body Ingestion (Fdry) Ingestion (Fwet) % body wgt FI

Class Weight (g bwt/day) (g/day) consumed (kg-diet/day)

15 3 14 95 1.43E-02

Herbivores/ 35 5 23 66 2.31E-02

insectivores 1000 31 153 15 1.53E-01

Dose-based EECs 

(mg/kg-bw)

Avian Classes and Body Weights (grams) Mammalian Classes and Body weight (grams)

small mid large small mid large

20 100 1000 15 35 1000

Termites 121.48 69.27 31.02 101.70 70.29 16.30

Dose-based RQs 

(Dose-based 

EEC/adjusted LD50)

Avian Acute RQs

Size Class (grams) Mammalian Acute RQs Mammalian Chronic RQs

20 100 1000 15 35 1000 15 35 1

Termites NA NA NA 0.01 0.01 0.00 1.85 1.58 0
-Page 33 of 36- 

Dietary-based RQs 

(Dietary-based 

EEC/LC50 or NOAEC)

RQs

Acute Chronic

Avian 0.05 3.63

Mammal N/A 0.21
-Page 34 of 36- 

Appendix C. Hexaflumuron Degradates 

Degradate Amounts Recovered in Submitted Studies

Fate Study Soil Type Phenylamine1 Phenylurea2

DBA3 M84 MRID

Hydrolysis not applicable

10%

(Day 33)

59%

(Day 37)

55%

(Day 33)

ND 426485-

26

Aerobic 

Soil 

Metabolism

Hanford sandy 

loam 12% (Day 30) ND ND 3% (Day 365)

426959-

01

Catlin silt loam 18% (Day 120) ND ND 5% (Day 365)

Alconbury clay 

loam 18% (Day 60) ND ND 7% (Day 365)

Castle Rising 

sandy loam 20% (Day 120) ND ND 11% (Day 180)

Anaerobic 

Soil 

Metabolism

Hanford sandy 

loam 16% (Day 60) ND ND 4% (Day 90)

426959-

01

Catlin silt loam 15% (Day 60) ND ND 5% (Day 90)

Alconbury clay 

loam 17% (Day 60) ND ND 5% (Day 90)

Castle Rising 

sandy loam 18% (Day 90) ND ND 2% (Day 90)

1. 3,5-dichloro-4-(l,l,2,2-tetrafluoroethoxy) phenylamine

2. 3,5-dichloro-4-(l,l,2,2-tetrafluoroethoxy)phenylurea

3. 2,6-difluorobenzoic acid

4. The degradate was not named nor was a structure provided, and it is unclear if it is a degradate separate 

from those already identified in other studies

ND = not detected

Fate Parameters For Hexaflumuron Degradates, Estimated Using EPISuite v. 4.0 

Chemical/Fate parameter Hexaflumuron DBA Phenylurea Phenylamine

Molecular Weight (g/mol) 461 158 321 278

Vapor Pressure (torr) 4.43 x 10-11 1.76 x 10-3 7.53 x 10-6 2.31 x 10-3

Octanol-water Partition Coefficient (Log 

KOW) 5.64 1.59 3.40 3.77

Water Solubility (mg/L; at 25 °C) 2.07 x 10-2 3,063 11.52 9.92

Henry's Law Constant

(atm-m3 mol-1) 9.96 x 10-10 1.20 x 10-7 2.76 x 10-7 8.52 x 10-5

Leaching/Mobility Koc (L/kgoc) 6,092 – 7,272* 11 – 44* 676 – 783* 1,108 – 1,482*

* Range of two values
-Page 35 of 36- 

Appendix D.

Acute Avian Risk Estimates

For birds, if the non-definitive endpoint (LD50>2,000 mg a.i./kg bw) is used to estimate acute 

risk, the calculated avian acute dose-based RQ value (0.12) exceeds the LOC for listed 

(LOC=0.1) small (20 g) birds. However, as the adjusted LD50 for small birds is 1,038 mg a.i./kgbw (equivalent to an internal dose in a 20-g bird of 20.76 mg a.i.), this is roughly equivalent to a 

small bird ingesting 64,875 termites (containing a steady state of 320 ng hexaflumuron/termite). 

Assuming each termite weighs 3 mg, the equivalent weight of the termites (195 g) is more than 8 

times what a small bird would be expected to eat in a day20. 

Acute Mammalian Risk Estimates

Using the non-definitive endpoint (Norway rat acute oral LD50 of >5,000 mg a.i./kg bw), the 

mammalian acute dose-based RQ values did not exceed the acute risk LOC for listed (LOC = 

0.1) or non-listed (LOC = 0.5) mammals. 

Chronic Avian Risk Estimate Example (small bird- 20 g bw)

Dietary Based Risk: 

29.4 mg a.i./kg-diet (NOAEC) x 23 g/day (wet food intake for small bird) x 1 kg/1000 g 

= 0.6762 mg a.i./day x 1,000,000 ng/mg 

=676,200 ng a.i./day x 1 termite/320 ng a.i. 

= 2113 termites x 3 mg /termite

= 6339 mg/day or 6.3 g/day, or about 1/3 of daily food intake (23 g/day). 

Chronic Mammalian Risk Estimate Example (small and medium mammal-15 and 35 g bw)

Dose Based Risk: 

Small Mammals: 

55 mg a.i./kg-bw (adjusted NOAEL) x 15 g (weight of small mammal) x 1 kg/1000 g

=0.825 mg a.i. x 1,000,000 ng/mg 

=825,000 ng a.i. x 1 termite/320 ng a.i. 

=2,578 termites x 3 mg /termite

=7,734 mg termites or 7.7 g termites, or about 55% of the daily food intake (14 g/day) of small 

mammal

Medium Mammals: 

44 mg a.i./kg-bw (adjusted NOAEL) x 35 g (weight of small mammal) x 1 kg/1000 g 

= 1.54 mg a.i. x 1,000,000 ng/mg 

= 1,540,000 ng a.i. x 1 termite/320 ng a.i. 

 

20 USEPA. 1993. Wildlife exposure factors handbook. Volume I of II. EPA/600/R-93/187a. Office of Research and 

Development, Washington, D.C. 20460.
-Page 36 of 36- 

= 4,812 termites x 3 mg /termite

=14,437 mg termites or 14.4 g termites, or about 63% of the daily food intake (23 g/day) of small 

mammal