with details regarding th e 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
hexaflumuro n 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 a nd 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 EFE D 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 contain in g 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 b y 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. Aqu atic 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 De scription

................................................................................................ ...................................... 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 . Th is
assessment is based on the best available information on the use, environmental fate and transport, and ecological effects data for hex aflumuron.

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

. The c ompound 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.

Hexaf lumuron'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 cha nce 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 asse ssment, 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 te rrestrial 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) reduc e 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 terrestria l invertebrates 3

, 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 adu lt 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 chr onic 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 non

target terrestrial animals including birds, mammals, amphibians and reptiles when used in
accordance with the current label s. EFED does not expect the current use of hexaflumuron as an

e nclosed 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

an d characterizing the risk (USEPA 1998a).

A preliminary Problem Formulation for the R egistration R eview 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,
2009 4

. 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 ; t hese revisions are captured
within the revised Problem Formulation 5 and used in this p reliminary 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 Pr otection 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. Hexaf lumuron 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 i n 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

- difluoro

benzoyl) urea

CAS name 1

- (3,5

- dichloro

- 4

- (1,1,2,2

- tetrafluoroethoxy)phenyl)

- 3

- (2,6

- difluoro

benzoyl) urea

Structure

Pesticide type Termi ticide

Chemical class Benzoylphenylurea

CAS number 86479

- 06

- 3 Empirical formula C 16 H 8 Cl 2 F 6 N 2 O 3 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 Program 6 . 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 below

ground termite bait station s. There are three active registered products containing hexaflumuron (Recruit ® AG, Registration Number 6271 9- 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, bottl ing 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 -ba sed 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 prote cts 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 act s as a short

- lived phagostimulant, which increase s 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 shrink

wrap is removed, and the bait cartridge is placed into the in

- ground te rmite 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

wra pping 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 in

ground termite stations in a given area is determined by the perimeter linear feet of the structure being attacked by termites. Per the label, t ermite 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 . R isks to non

- target organisms have been calculated using

con servative 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 st ressor 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 spe cies, 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 pe sticide 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” studies 7 ). 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 hexaflu muron 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 evaluat e the potential ecological effects of pesticides to these non

- target taxonomic groups and a summary of the acute toxicity classification for each tax on.

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

Birds 1 Mallard duck ( Anas platyrhynchos ) Bobwhite quail ( Colinus virginianus ) Practically n on

- toxic to slightly toxic

Mammals Laboratory rat ( Rattus norvegicus ) Practically n on

- toxic

Insects Honey bee ( Apis mellifera L. ) Practically non

- toxi c 3

Freshwater fish 2 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 t o 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 hexa flumuron 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 hexaflumuro n, 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 ecologic al 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 di agram (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 term i ti cide, p otential 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 Hypothesi s

For hexa flumuron , 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 inclu ding birds, mammals,amphibians and reptiles when used in accordance with the current label. These nontarget organisms include listed species as well as non- listed spec ies.

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. , wate r 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 / Terrestrial

phase 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
th ereby transporting it away from the bait station to nests

. Once in side the termite, hexaflumuron could be transferred to termite predators (animals that consume termites) . Based
on the octanol- water partition coefficient ( K ow = 2.9x10 5 ) and the organic carbon partition coefficient ( K
oc range: 6,092 – 7,272 L /kg
oc ) 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 s urrogate 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 assessme nt utilizes surrogate species to represent all freshwater fish (2000+) and bird (680+) species in the
U.S . In addition, t he 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 LD 50 (Lethal Dose),
LC 50 (Lethal Concentration) , and EC 50 (Effects Concentration ). These are measures of acute toxicity which res ult 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
fresh water 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 en vironmental

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

D398118. 3/22/12.- Page 13 of 36
- concentrations (EEC s ) by acute and chronic toxic ity values. The resulting RQs are then compared to the Agency’s L evels of C oncern (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 potenti al to cause adverse e ffects to non- target organisms.

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

R isk C lass R isk D escription RQ LOC

Terrestrial Animals (mammals and birds)

Acute Potential for effects to non

- listed animals from acute

exposures EEC/LC 50 (Dietary) 0.5 EEC/LD 50 (Dose)

Acute
Restricted Use Potential for effects to animals from acute exposures Risks may be mitigated through restricted use classification EEC/LC 50 (Dietary) 0.2 EEC/LD 50 (Dose)

Acute Listed Species Listed species may be potentially affected by acute

exposures EEC/LC 50 (Dietary) 0.1 EEC/LD 50 (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 station s. There are t hree active Section 3 products containing hexaflumuron (Recruit ® AG, Registration N umber 62719 -270, Shatter ® , R egistrat ion N umber
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 operators 10

. 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 provide d 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 ) 4.4 3 x 10 - 11 426485

- 05 Acceptable

Octanol

- water Partition Coefficient ( K
ow ) 2.90 x 10 5 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 half

life (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 K

oc (L/kg

oc ) 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 ., above
and below

- ground bait stations), the material will not be subject to photodegradation when used as proposed. K
oc estimates from the Estimation Program Interface Suite (EPISuite TM ; 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 o ctanol

- water partition coefficient K
ow =2.90x10 5 ), and predicted slight mobility in soil
based on K
oc (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 stat ions “ 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 restri ctions 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 EPISuite TM ( 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 metab olism study (MRID 426959

- 01)

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

con ditions, 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 patt ern 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
h exaflumuron. Bioconcentration and bioaccumulation factors (BCFs and BAFs, respectively) were estimated for hexaflumuron using the K
ow (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 , g iven hexaflumuron’s high log K
ow value (log K
ow =5.46), there also exists the potential for hexaflumuron to bioaccu mulate 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 (ECOSAR TM ) component of EPISuite TM , 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 assess es 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 registrant

submitted study ( MRID 455167 -25 ) measur ing the uptake rate of 0.5% 14 C- 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
termi te 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 termite s . 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 107 1 121.48 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 * BW 0.651 ) / (1
- W )

• Mammal consumption : FI = (0.621 * BW 0.564 ) / (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 re ported in the Preliminary Problem
Formulation for Registration Review 11 . 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 concentration s exceeded the highest concentration s 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 animal s 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 M ost S ensitive E ndpoints from S ubmitted A quatic T oxicity S tudies for

H exaflumu ron.

Species

(common name) Taxa Represented End

point Duration (hours) Mean
concentration

(μg a.i./L) Citation

MRID Study
Classification

Lepomis
macrochirus (b luegill s unfish) Freshwater
fish and aquatic

- phase amphibians LC 50 96 >255.6 * 426485

- 11 Supplemental

Practically

non

- toxic

Onchorynchus mykiss

( r ainbow t rout) > 535.5 * 426485

- 12 Supplemental

Practically

non

- toxic

Daphnia magna (w ater f lea) F reshwater

i nvertebrates LC 50 48 0.111 426485

- 13 Acceptable

Very highly

toxic *Exceeds the solubility limit (27 μ g/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, hexafl umuron 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 tox icity 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 summariz ed
here and used to inform th e 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 e ither generation. The LOAEL fo r 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 wa s 29.4 mg ai./kg- diet (mean

- measured) and the LOAEC wa s 96.5 mg ai./kg

- diet (mean

- measured) based on reduced survival ( i.e ., reduced numbers of viable embryos and hatchling surviv al ) and reduced growth ( i.e ., hatchling body weights). Conclusions for birds we re assumed to apply to terrestrial

phase 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 EFED 13

. Tests using TGAI and adult bees yielded acute contact and oral 48

- hr LD 50 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 s tudies conducted with a formulated end

- use product containing hexaflumuron (Consult ® 100 SC; 10% hexaflumuron) t he LD 50 value for the acut e contact toxicity test was 5.83 (95% confidence interval: 5.10-6.74) μg a.i./bee. The LD 50 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 unc ertain ty regarding how the results of
these test s relate to hexaflumuron products registered in the U.S.

Table 3.4. Summary of M ost S ensitive Endpoints f rom S ubmitted T errestrial T oxicity S tudies for

H exaflumuron.

Species

(common name) Taxa Represented End

- point Mean
Concentration Citation

MRID Study
Classification
, Acute Toxicity
Classification

Rattus norvegicus

(l aboratory r at) m ammals Acute Oral

LD 50 >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

(m allard d uck) b irds,
terrestrial

- phase amphibians and reptiles Acute Oral

LD 50 >2,000 mg/kg
bw 426485

- 08 Acceptable

Practically

non

- toxic

Avian Reproduct i on

NOAEC 29.4 mg a.i./kg

diet 483232

- 05 Supplemental

Colinus virginianus

(n orthern b obwhite

q uail) b irds,
terrestrial

- phase amphibians and reptiles Subacute Dietary

LC 50 2,201 ppm 426485

- 09 Acceptable

Slightly toxic

Apis mellifera ( Honeybee) Terrestrial
invertebrates Contact LD 50 >99.6 μg a.i./bee

483232

- 08 Acceptable

Practically

non

- toxic Oral LD 50 >99.6 μg a.i./bee

TEP Contact

LD 50 5.83 μg a.i./bee

483232

- 07 Supplemental

Moderately

toxic TEP Oral

LD 50 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 Of fice 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 inci dents 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 wi th 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 i ndex 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 re mainder of the reports concerned individuals that had accidentally ingested or believed they had become exposed to hexaflumuron through misuse/non- registered use s.



### 4. Risk Characterization

4.1. Risk Estimation

This screening

- level assessment of the label ed 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 to xicity 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 exce e dances 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 a re non- definitive (‘ greater than’ values; see
Table 3.4 ), R Qs 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 LC 50 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 res ultant RQ value (3.63) exceeds the chronic risk LOC (1.0)

. For this RQ estimate, small birds are assumed to consume rough ly 1/3 of their diet as termite s containing hexaflumuron (2,113 termites/day) to result in reproductive toxicity to birds.

Chronic dose

- based risks a re not calculated for birds as a chronic dose

- based endpoint i s not available (the dietary

- based avian NOAEC was used to estimate chronic risks).

For mammals, chronic risk i s calculated on a dietary basis and on a per

- dose basis. D ietary

based risks for mammals resulted in an RQ of 0.21 which does not exceed the LOC (1) for
chronic mammal risk. T he c hronic dose

- based RQ values a re 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 r isk estimates exceed the chroni c 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 3.6 3 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 exce e ds 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 ( b ased on the nondefinitive Norway rat acute oral

LD 50 of >5,000 mg a.i./kg bw) did not exceed the acute risk LOC for listed (LOC = 0.1) or non

listed (LOC = 0.5) mammals. For birds, if the non

- definitive endpoint (LD 50 >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. Howe ver, as the adjusted LD 50 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/termit e). 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 day 14 . For a

14 USEPA. 1993. Wildlife exposure factors handbook. Volume I of II. EPA/600/R

- 93/187a. Of fice 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 assu med 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
likelih ood of chronic adverse effects to birds is low.

F or 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 r isk 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 t o 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 ba sed on conservative assumptions, the registered use pattern (bait stations) makes exposure to wildlife un likely , as hexaflumuron is used in residential
and semi

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

- target

ter restrial 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
constituen t 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 1997 15 ). 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 weigh ing less than 7 mg at colony foundation (Long 2005 16 ), 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 o ther opportunistic insectivore s (Nutting, 1969 17 ). 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

.

F or terrestrial invertebrates, toxicity data are available for adult bees. Toxicity d ata are not available for larval bees, which would be expected to be susceptible to hexaflumuron based on the mode of action (molting inhibition). How ever, 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 stu dies with honey bees

, where the formulated product (Consult 100 SC, 10% a.i.) is moderately toxic, while the TGAI is practically non -toxic. Th is formulated product
is not used in the United States

. While EFED recognizes there are some species of terrestr ial 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 risk 18 :

1.) Not all of the bait material is available o ver the entire exposure period

. The baits are designed to contain enough material to last at least 6 months under the heaviest foraging
conditions. So me 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. Fli ght 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 wha t 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 depos ited 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” termite s. 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 wi thin 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 i n accordance with the current label s.

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 statio ns, 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 potent ial 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 K
ow value (log K
ow >5) there also exists the potential for hexaflumuron to bi oaccumulate 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 tox ic 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 ec ological risk posed to aquatic vertebrat es, invertebrates, and plants by hexaflumuron.

In the terrestrial environment, it is un likely 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 indicate s a potential for chronic risk to birds and mammals ( Table 4.1 ). However, the LOC exceedance for
birds and mammal s is based on conservative assumptions described above in Section 4.2 , Risk Description

. Based on t he s creening 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 (L isted) 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 non

target organisms.

• Low solubility and high K

oc limit mobility and decrease likelihood for exposure to

non

- target organis m. 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 non

target organisms. Low solubility and high K

oc limit mobility and decrease likelihood for exposure to non

- target organism. Indirect Effects 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 non

target 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 non

target 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 maturati on, 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),
hexaf lumuron 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/da ta 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 19 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 G uidance

Long. CE 2005. Reticulitermes flavipes (Isoptera: Rhinotermitidae) colonies: reproductive lifespans, caste ratios, nesting and foraging dynamics, and genetic architecture. (Doctoral dissertation). A bstract a vailable 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. 2007 b . Ecological Incident Information System. http://www.epa.gov/pesticides/science/efed/policy_guidance/team_authors/endangered_species_ reregistration_workgroup/esa_incident_guida nce.htm#searching

USEPA. 2007 c . 40 CFR Part 158. Pesticides; Data Requirements for Conventional Chemicals: Final Rule. 72 FR 60934. October 26, 2007.

US EPA. 2007 d . 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 ( 14 C) 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 Qu ail: 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)

termit e 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

Herbiv ores/ 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 Phenylamine 1 Phenylurea 2 DBA 3 M8 4 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

K OW ) 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

- m 3 mol -1 ) 9.96 x 10 -10 1.20 x 10 -7 2.76 x 10 -7 8.52 x 10 -5

Leaching/Mobility K

oc (L/kg

oc ) 6,092

– 7,272* 11

– 44* 676

– 783* 1,108

– 1,482* * Range of two value s- Page 35 of 36
- Appendix D.

Acute Avian Risk Estimates For birds, if the non

- definitive endpoint (LD 50 >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 LD 50 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 day 20

.

Acute Mammalian Risk Estimates Using the non

- definitive endpoint (Norway rat acute oral LD 50 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 E stimate Example (small and medium m ammal -15 and 35 g bw)

Dose Based Risk :

Small Mammals:
55 mg a.i./kg

- bw (adjusted NOAE L ) x 15 g (we ight 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