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MEMORA DUM February 17,2010

Subject: EFED Response to Comments on the Problem Formulation for Hexaflumuron

Elizabeth Behl, Chief

Environmental Risk Branch 4

Environmental Fate and Effects Division

Office of Pesticide Programs

Chuck

Kristina

Peck

Garber

Environmental

, Biologist

Enginee '<JolI ....... 'a

Environmental Risk Branch 4

Y.-........-

Russell a em, Chemical Review Manager

Thomas Moriarty, Team Leader

Reregistration Branch

Pesticide Reregistration Division

Office of Pesticide Programs

From:

Through:

To :

Based on comments rece ived and EFED's responses (contained in this memo), EFED has revised

its preliminary problem formu lation. This revised problem formulation is attached.

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1. DAS reports referenced in comments are available to the Agency 

DAS Comment (p. 36):

Please note that all reports referenced within this [DAS’s comment] document are available to 

the Agency upon request. 

EFED Response: 

DAS references several studies that may be relevant to fulfill data gaps identified in EFED’s 

problem formulation, including: acute oral toxicity of hexaflumuron to honey bees (nonguideline), avian reproduction (guideline 850.2300) and terrestrial plant toxicity (guideline 

850.4100). EFED requests that DAS provide the studies listed below (that were referenced in 

DAS’ comments) so that they may be evaluated by EFED. If these studies are found to be 

acceptable, they may be used to fulfill the relevant data requirements. The requests for studies in 

the current data call-in (for acute oral toxicity of hexaflumuron to honey bees, avian reproduction 

and terrestrial plant toxicity) accurately represent current data gaps; EFED is not modifying these 

requests at this time. 

Cole, J. H. The Acute Contact and Oral Toxicity To Honey Bees of XRD 473. 

Unpublished report of Dow AgroSciences DET 645, 02-SEP-1985. 

Hakin, B., Anderson, A., and Chanter, D. O. The Effects of Dietary Inclusion of XRD 

473 Technical on Reproduction in the Bobwhite Quail. Unpublished report of Dow 

AgroSciences GHE-T-184, 19 October 1988. 

Hakin, B., Anderson, A., and Chanter, D. O. The Effects of Dietary Inclusion of XRD 

473 Technical on Reproduction in the Mallard Duck. Unpublished report of Dow 

AgroSciences GHE-T-192, 10 October 1988. 

Paterson, E. A., Toft, A. Evaluation of the pre-emergence phytotoxicity of hexaflumuron 

in a herbicide screen -2005. Unpublished report of Dow AgroSciences GHE-P-11276, 

01-Dec-2005. 

DAS also referenced several aquatic toxicity studies that have not been received by the Agency. 

These studies may provide information on the acute toxicity of hexaflumuron to estuarine/marine 

invertebrates, chronic toxicity to freshwater invertebrates and toxicity to algae. EFED requests 

that DAS submit the studies referenced below so that they can be evaluated. 

Thompson, R. S. XRD 473 Technical: Acute Toxicity to the Brown Shrimp. Unpublished 

report of Dow AgroSciences 1055, 29 March 1988. 

Nozawa, T. and Annou, E. Acute Toxicity of XRD 473 to Suji Shrimp. Unpublished 

report of Dow AgroSciences GHF – R 159, 8 December 1988. 
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Maeda, M. and Funaki, K. Acute Toxicity of XRD 473 to Kuruma Prawn. Unpublished 

report of Dow AgroSciences GHF – R 157, 8 December 1988. 

Jenkins, W. R., Jenkins, C. A., and O’Connor, J. The Effect of XRD 473 on the Survival 

and Reproduction of Daphnia magna. Unpublished report of Dow AgroSciences DET 

1153, 5 September 1988. 

Smyth, D. V. and Thompson, R. S. XRD 473: Determination of Toxicity to the Green 

Algae Pseudokirchneriella subcapitata (formerly Selenastrum capricornutum). 

Unpublished report of Dow AgroSciences GHE-T-224, 19 August 1988. 

2a. Clarification of hexaflumuron use 

DAS Comment (p. 22 and 36):

DAS needs to clarify how the hexaflumuron-containing bait is used in a termite baiting system. 

First, hexaflumuron, which is formulated in a termite bait (Shatter, Recruit AG), is used to 

protect residential, commercial, and historical structures from wood-destroying subterranean 

termites. Recruit AG and Shatter contain a cellulose-based bait formulation (bait matrix) with 

the active ingredient hexaflumuron, both of which are labeled for termite control. The bait is 

used both above ground (Recruit AG, generally indoors) and in-ground (Shatter) for the 

elimination of subterranean termite colonies. The bait matrix base is cellulose compressed into 

dry oblong briquettes approximately 5/8 inch long by 3/16 inch diameter and is contained in a 

sealed plastic bag for Recruit AG and within a bait cartridge for Shatter. This results in a solid 

formulation containing essentially no dust, dramatically reducing the potential for inhalation 

exposure. In-ground uses of Shatter utilize a device that consists of a rigid plastic tube with 

termite access slots covering the surface of the tube and is called a bait cartridge. The bait 

cartridge has slots (not holes) to allow termite access to the bait. The sturdy plastic outer tube 

referred to in the Agency’s document is known as the termite station and is not the same as the 

Shatter bait cartridge. The commercial wood monitoring devices are not stapled together along 

one edge. Instead, monitoring devices are simply two pieces of wood coupled with an extractor 

(used to pull the monitoring devices out of the termite stations); or alternatively, monitoring 

devices can be an electronic version called ESP which has the two pieces of wood held together 

by glue spots alone or by glue spots and brads. According to the directions for use, placement of 

termites into the Shatter bait cartridge is optional at the discretion of the pest management 

professional. During the baiting step of the service, the Shatter bait cartridge is placed into a 

rigid plastic termite station. While residences may be treated using Recruit AG and Shatter, the 

installations are performed only by pest management professionals licensed by the State to apply 

termite control products. Homeowners do not contact the bait which is either inside a plastic bag 

within an above-ground station (Recruit AG) or inside of a bait cartridge (Shatter) placed into a 

termite station. 

Upon initial insertion into the ground, the termite station typically contains a wooden monitoring 

device (untreated with pesticide). Several termite stations are installed around a termite-infested 

structure as specified in the labeling. After the indication of termite feeding is observed on the 
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untreated wooden monitoring device, the cap of the hard plastic termite station is removed and 

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

cellulose-based bait matrix formed into briquettes containing 0.5% hexaflumuron (250-275 mg 

hexaflumuron per bait cartridge). Each 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, up to 80 mL of water or sports drink may be added to the bait 

cartridge and allowed to soak into the cellulose-based bait matrix briquettes. 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 termite station with the top cap of 

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

human contamination of the bait cartridges (which may deter the termites from feeding), 

installers may choose to wear gloves during the preparation of the bait cartridge. 

The hexaflumuron-containing briquette formulation (within a bait cartridge for Shatter or within 

a plastic bag inside of an above-ground station for Recruit AG) is applied only when and where 

termite activity has been detected. At any one site, the majority of the termite stations contain 

untreated wood (monitoring devices), for monitoring purposes. In a “worst-case” scenario, four 

adjacent homes each with a 1⁄4 acre property could be infested with a termite colony, and be 

treated simultaneously with Shatter termite bait. Of the approximately 100 below-ground termite 

stations, during a typical year approximately 12-16 termite stations would contain hexaflumuron 

bait while the remainder would contain only untreated wood monitoring devices. This calculates 

to approximately 3.15-4.20g hexaflumuron per acre as an upper level “rate” to eliminate the 

damaging termite colonies. To further illustrate the minimal environmental exposure, between 

2005 and 2008, less than 3000 g of hexaflumuron were sold in the U.S. per year, as less than 600 

kg of formulated bait in bait cartridges were sold to pest management professionals per year. 

After termite colony elimination, or any time when termites cease feeding on the bait, the bait 

cartridge is removed and disposed of according to label directions.

EFED Response: 

EFED will revise the problem formulation to reflect the information in the comment; however, 

the information does not alter EFED's understanding of the potential risk to non-target animals 

associated with the uses of hexaflumuron (i.e., through exposure of non-target mammals, birds, 

reptiles and amphibians to hexaflumuron through consumption of termites, exposure of nontarget insects through entry into bait stations). DAS should consider more detailed labeling in 

order to further reduce the potential scope of the assessment and associated uncertainties. 

2b. Clarification of hexaflumuron use 

DAS Comment (p. 28):

Shatter termite bait is contained in a bait cartridge which is placed into a termite station during 

the baiting step. The in-ground termite station does not contain any termite bait (no pesticide) 

and therefore does not have any information relevant to amount of bait. However, the Shatter 
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bait cartridge itself does have an affixed label that discloses the amount of bait in the cartridge. 

In addition, the Recruit AG (above-ground) station itself does have an affixed label on it that 

discloses the amount of bait in this station. The maximum number of in-ground termite stations 

on an area is determined by the perimeter linear feet of the structure being attacked by termites. 

Termite stations are placed in the ground around the perimeter of the structure at intervals no 

greater than every 20 feet. 

At this time, the above-ground termite bait product, Recruit AG is registered for use in the U.S. 

but is not commercially available. 

The following pertains to Shatter termite bait which is commercially used in the marketplace. 

DAS has over 15 years of use experience with termite baiting systems. The following scenarios 

represent use patterns based on DAS’ market experience. A Shatter bait cartridge contains 50 to 

55 grams of the 0.5% hexaflumuron bait. On average, 3 to 4 bait cartridges are used at a 

termite-infested structure during the baiting step. As a maximum, very large structures with 

multiple termite colonies may require up to 50 bait cartridges over time while an average home 

with multiple termite colonies may require up to 12 bait cartridges over time. However, these 

types of events are rare. The minimum use would be one bait cartridge per structure. 

High-density home example: one average-sized home has about 225 liner feet of perimeter (75 

foot x 38 foot footprint). Four such homes can be placed onto an acre using four 1⁄4 acre lots. The 

total perimeter linear feet of the four structures would calculate to about 900 feet. Each home 

would have an average of 23 to 25 termite stations installed. Total termite stations installed 

would be about 100 “per acre” for all four homes. From use experience, approximately 12 to 

16% of the installed termite stations will be hit by termites. This translates to 12 to 16 bait 

cartridges used per acre to treat these four homes which calculates to 3.15 to 4.20 grams of 

active ingredient hexaflumuron per acre. 

EFED Response: 

DAS recommendations of how these termite stations should be installed would be useful for 

homeowners if available on the label. Given the current label language, a licensed applicator is 

not restricted on the maximum amount of product that can be applied at a specific location. DAS 

makes the claim that the “maximum number of in-ground termite stations on an area is 

determined by the perimeter linear feet of the structure being attacked by termites” and that 

“termite stations are placed...at intervals no greater than 20 feet” (emphasis added); however, 

there is no minimum separation distance provided on the product labeling. Therefore, it is 

possible, however unlikely, that, for a perimeter of 225 feet, 550 termite stations containing 

Shatter® termite bait could be placed right next to each other (assuming the limiting factor, the 

ground cover plate, is 6 inches in width, yielding 2 stations per foot). This does not take into 

account repeated replacement of the Shatter termite bait cartridge when the material in the bait 

cartridge is nearly or totally consumed. 

EFED will consider the historical use information and estimates provided in the comment above 

in evaluating exposure of non-target organisms to hexaflumuron. DAS should consider more 
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detailed labeling in order to further reduce the potential scope of the assessment and associated 

uncertainties. 

Even though the above ground product is not currently being marketed, the Agency must 

evaluate the use pattern to ensure that there are sufficient data to support the registration. 

3a. Fate of hexaflumuron in the environment 

DAS Comment (p. 33):

 

EPA presents Appendix C. Data Call-In Tables on pages 29 through 34: 

• Guideline Number: 835.4100; Study Title: Aerobic Soil Metabolism 

• Guideline Number: 835.4200; Study Title: Anaerobic Soil Metabolism 

• Guideline Number: 835.1230/1240; Study Title: Leaching/Mobility Study 

• Guideline Number: 850.2300; Study Title: Avian Reproduction Tests 

• Guideline Number: Non-guideline; Study Title: Acute oral toxicity to honey bees 

• Guideline Number: 850.3040; Study Title: Field Testing for pollinators 

• Guideline Number: 850.4100; Study Title: Terrestrial Plant Toxicity Test, Tier 1 

Hexaflumuron cannot be classified as readily biodegradable (4). In aerobic soils, hexaflumuron 

first-order degradation half-life values ranged from 108-255 days (5). In this study, two aerobic 

soil metabolism products were identified from the 14C-aniline-labeled hexaflumuron. The two 

corresponding compounds resulting from the 14C-benzoyl-labeled hexaflumuron were presumed 

to be transient and quickly degraded to 14CO2. The identity of the amine degradate was 

confirmed by GC-MS. The urea degradate never exceeded 11% Applied Radioactivity (AR) in 

any soil, while the amine degradate reached a maximum of 20% AR at 120 days after treatment 

(DAT) in one soil before declining. Another unknown, M8, was present at a maximum of 11% AR 

at one time point (180 DAT) in one soil, but was generally present at <7% AR. M8 was 

characterized by TLC as the radioactivity remaining at the origin. It is likely that M8 is a result 

of poor chromatography since it was not observed using a second TLC system (p. 70, both 365 

DAT CR1 soil data). No other single component accounted for more than 7% AR. Amine and 

urea were the only metabolites observed following aerobic soil degradation of aniline-labeled 

noviflumuron, which is similar to hexaflumuron (molecular weight of 529.15, +1C, +3F, -H) (6). 

In general, in the 14C-benzoyl-labeled samples the amount of 14CO2 approached 17-24% of 

applied radioactivity after 1 year. Since the amount of applied radioactivity in the volatile traps 

did not increase appreciably, especially after 270 DAT, there may have been incomplete 

trapping, therefore accounting for the low mass balance at 365 days. The radioactivity in the 

NaOH traps was confirmed as 14CO2 by precipitation of the radioactivity from the trapping 

solution on addition of aqueous barium chloride solution. A supplemental study (also reported 

within Ref. 5) was designed to overcome inefficient trapping of volatile CO2 radioactivity and/or 

low efficiencies in the method of measurement of radioactivity. The supplemental study used a 

higher concentration of NaOH to trap volatiles for up to 180 DAT. Good accountability, >90% 

was achieved in the supplemental study (5). 
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Bound radioactive residues increased throughout the incubation period, reaching 45-70% and 

20-25% in the aniline-label and benzoyl-label, respectively, after 1 year. For comparison, 38-

46% of applied benzoyl-labeled noviflumuron was recovered as 14CO2, and material balance 

was 88.8-103% AR at 365 DAT (6) further supporting the conclusion that insufficient trapping 

was the cause of the lower hexaflumuron mass balances. 

The degradates from the benzoyl portion of the hexaflumuron are transient, degrading quickly to 

CO2. These metabolites would not accumulate in the environment. The amine and urea 

degradates from the aniline portion of hexaflumuron are slightly more polar than hexaflumuron. 

Based on structural comparison to degradates of a similar molecule, noviflumuron, which has a 

molecular weight of 529.15 (+1C, +3F, -H), the hexaflumuron amine and urea are unlikely to be 

mobile in soil and are unlikely to pose a risk to groundwater. The apparent Kd values for the 

noviflumuron aniline-labeled metabolites were comparable to slightly lower than for 

noviflumuron, suggesting that the metabolites are immobile (6). The average apparent Kd values 

for the noviflumuron urea and amine metabolites were 19.5 and 39.0 mL/g, respectively, with 

corresponding KOC values of 2,478 and 3,983 mL/g. 

A study to determine the anaerobic soil metabolism should not be required since exposure of 

hexaflumuron in the termite bait system is unlikely to be exposed to anaerobic soil conditions. 

However, information is available to demonstrate that hexaflumuron degraded more rapidly 

under anaerobic conditions than under aerobic conditions (5) with a half-life of 40-72 days. The 

low mass balance can reasonably be attributed to insufficient 14CO2 trapping, since the original 

system used in the aerobic soil metabolism study was employed. It would therefore be reasonable 

to conclude that acceptable mass balance would have been achieved with a higher NaOH 

concentration, but that the remaining results including half-life would not differ. 

Results indicate that hexaflumuron will be moderately persistent in soil under aerobic 

conditions, but due to the formulation of this highly-sorbed compound in a cellulose bait matrix 

enclosed in a protected, in-ground plastic termite station, it is unlikely that significant quantities 

of hexaflumuron will reach the soil environment. 

EFED Response: 

As discussed in the problem formulation, the combined aerobic and anaerobic soil metabolism 

study (MRID 426959-01) was classified as supplemental. The aerobic metabolism study did not 

fulfill the data requirements because: (1) one major degradate (M8 at 11% of the applied rate at 

180 days) from the aniline-labeled study was not identified; and, (2) a low material balance (up 

to 55% of the applied radioactivity was not accounted for by the termination of the study) in the 

benzoyl-labeled portion of the study prevented reliable interpretation of the data. The review of 

the study did show, as DAS indicates in its comments above, that the use of a higher 

concentration of NaOH to trap volatiles in a supplemental study did provide better material 

balances for two of the soils in the study (Castle Rising sandy loam and Hanford sandy loam). In 

both tests, the amounts captured in the volatile traps in the supplemental study were significantly 

higher than the amounts captured in the initial study volatile traps. In the study, M8 was 

characterized by the study author as “more polar than any of the available reference compounds” 

(pg 34 of study), but was never identified and no explanation was provided. DAS’ argument that 
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the “M8 is a result of poor chromatography” does not appear to be consistent with data showing 

that M8 appears in several TLC systems/soil analyses (TLC system 6 (pg. 68, 72), TLC system 7 

(pg. 70)). As such, the aerobic soil metabolism study will remain classified as supplemental and 

the data requirement will remain unfulfilled. 

In the anaerobic soil metabolism study, the benzoyl-labeled portion of the study was not 

acceptable because of low material balances (up to 60% of the applied radioactivity was not 

accounted for by the termination of the study). The results of the supplemental study using a 

higher concentration of NaOH in the volatile trap did show a slight improvement, but did not 

provide an acceptable material balance. In the Hanford sandy loam soil, the overall material 

balance increased from 40.43% to 54.43% of the radioactivity at 60 days. In the Castle Rising 

sandy loam soil, the overall material balance increased from 72.6% to 74.29% of the 

radioactivity at 60 days. As such, the anaerobic soil metabolism study will remain classified as 

supplemental and the data requirement will remain unfulfilled. 

Given the deficiencies noted above, EFED considers the lack of acceptable aerobic and 

anaerobic soil studies as a data gap. However, EFED also agrees that the hexaflumuron will not 

readily degrade in aerobic or anaerobic soils. As such, EFED has agreed to waive the data 

requirements for OPPTS Guidelines 835.4100 (Aerobic Soil Metabolism) and 835.4200 

(Anaerobic Soil Metabolism). 

3b. Fate of hexaflumuron in the environment 

DAS comment regarding need for additional Leaching and Mobility studies (p. 34): 

In conjunction with low water solubility and confinement of hexaflumuron in the cellulose 

matrix, the available data indicate that hexaflumuron will be strongly sorbed and immobile. The 

un-aged leaching in four soils (2 US and 2 EU) in duplicate (one replicate per radiolabeled test 

substance) was originally reported by Yon and Morrison and summarized by Racke (7). This 

study concluded that “under the test conditions employed, with a simulated rainfall of 20 inches, 

hexaflumuron did not leach in four agricultural soils.” Hexaflumuron remained in the top 5 cm 

of soil. The report further concluded that hexaflumuron was not degraded in the soil. Also, the 

aerobic soil metabolism study (5) calculated apparent KOC values of 5338-70977 mg/L. 

Therefore, the immobility of hexaflumuron is clearly characterized without need for further 

testing. 

A batch equilibrium adsorption and desorption study was conducted with the analog 

noviflumuron. At four dose concentrations ranging from 0.010 to 0.097 mg/L, noviflumuron 

adsorption Kd values were greater than 850 mL/g and KOC values were greater than 32,000 mL/g 

(8). In this study, Dow adsorption Kf values ranged from 557 to 5,840 mL/g, averaging 2,280 

mL/g. The data reported by Racke (7) would indicate that similar values would be obtained for 

adsorption of hexaflumuron. 

Furthermore, a study to simulate the flooding of hexaflumuron-containing bait (9) demonstrated 

that the soil around the baited termite station will act as a physical barrier of the cellulose and 
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as a sorption matrix for hexaflumuron. In the event of flooding of a termite station containing 

hexaflumuron-formulated cellulose bait matrix, a small percentage (<0.025%) of the formulated 

material may move out of the baited termite station. However, the presence of soil will mitigate 

any movement of hexaflumuron into the surrounding environment; less than 0.000053% of the 

hexaflumuron in the cellulose bait matrix was detected in the water that passed through a small 

column of soil. 

These data clearly demonstrate the immobility of hexaflumuron, particularly when properly used 

in baited termite stations. DAS agrees with the EFED statement that, “exposure from runoff from 

the bait stations should not be an issue” (10). 

EFED Response: 

Regarding the study referenced by DAS (MRID 42648527), it was qualitatively determined that 

hexaflumuron was relatively immobile. The un-aged leaching portion of the mobility/leaching 

study was found to partially satisfy the data requirements by providing mobility data for the unaged parent. Hexaflumuron was not considered mobile in silt loam, clay loam, and two sandy 

loam soils. However, the aerobically-aged mobility part of the study was classified as not 

acceptable because of the experimental design and the statistical methods used by the study 

authors. 

In standard batch equilibrium experiments, pesticide-free soil is equilibrated with solutions 

containing individual degradates or parent to determine the amount of material adsorbed from 

the solution onto the soil. The soil containing the adsorbed compound of interest is then 

equilibrated with pesticide-free solution to determine the amount released from the soil to the 

solution (desorbed). In the aged mobility experiment described in this study, 14C-labeled 

hexaflumuron was incubated in four soils under aerobic conditions for 30 days; the 14C residues 

were then extracted from the soils by shaking three times with pesticide-free calcium chloride 

solution. The study authors assumed that during aging the hexaflumuron had adsorbed to the soil, 

and referred to all three equilibrations as "desorption." The soils were then further extracted with 

acetone and sodium hydroxide to determine the amount "adsorbed" to the soil. The registrant 

then calculated “Kd” values by dividing the amounts of hexaflumuron and each degradate 

remaining on the soils after the calcium chloride extractions by the amounts of hexaflumuron and 

each degradate found in the combined calcium chloride extracts. 

EFED determined, based on qualitative estimates of desorption coeffecients (Kdes), that 

hexaflumuron and its phenylamine and phenylurea degradates are not easily desorbed in the soils 

tested and that the benzoic acid degradate would be considered easily desorbed. No inferences 

could be made concerning adsorption coefficients (Kads) of the degradates, since adsorption of 

the degradates could not be separated from other processes occurring during metabolism in the 

soil. As a result, the aerobically-aged mobility part of the study was classified as not acceptable 

and the data requirement will remain unfulfilled. 

With regards to the novaflumuron data, novaflumuron has an additional -CF3 attached to the end, 

as well as an additional fluorine on the aniline ring. In the aforementioned study (MRID 

45516709), the test material was uniformly labeled on the aniline ring. It is unclear what effect 
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the additional fluorine molecule would have on the adsorptive behavior of novaflumuron and 

whether or not hexaflumuron would behave the same way. 

EFED has recently reviewed the flood study (MRID 47806601) submitted by DAS and has 

found that the information provided in the study qualitatively indicates that leaching from an 

actual bait station during “flooding” conditions would most likely be minimal and that 

hexaflumuron does not appear to migrate through 1 inch of soil (<0.00006% through 25 mm of 

soil). It should be noted, though, that only one soil type (Charentilly) was used in the analyses 

and it was unclear if that soil type is adequately representative of soil conditions found in all of 

the areas in United States where the product may be used. 

Given the deficiencies noted above, EFED considers the lack of an acceptable leaching and 

adsorption/desorption study as a data gap. However, EFED also agrees that hexaflumuron is not 

likely to be mobile in soils. Estimates from EPISuite (KOC=7272), as well as the qualitative 

information provided in the flood study (MRID 47806601), indicate that hexaflumuron will not 

easily migrate in soil. As such, EFED has agreed to waive the data requirement for OPPTS 

Guideline 835.1230/1240 (Leaching and adsorption/desorption). 

3c. Fate of hexaflumuron in the environment 

DAS Comment: Pesticide Entry into the Environment (p. 38):

The physical-chemical properties of hexaflumuron, such as the low water solubility and strong 

adsorption to soil, will prevent movement of hexaflumuron out of the baited termite stations. In 

addition, hexaflumuron that remains associated with the cellulose matrix (adsorbed) will be 

physically restrained from movement in the soil. The only route of entry for the hexaflumuron 

(<3000 g a.i./year, <5 g a.i./acre) from the Shatter in-ground bait cartridges is transport via 

termites. This is a biologically insignificant concentration, especially given the low toxicity 

reported below. 

Since hexaflumuron is used for control of subterranean termites, the dosed termites will not be 

exposed above ground. Subterranean termites move through enclosed, sturdy mud tunnels rather 

than becoming exposed above ground. Therefore, the dosed termites will not be readily exposed 

and available as a food source to predators. 

Other ground-burrowing mammalian predators are either too large to get their heads inside the 

slots of the termite station or bait cartridge or do not consume cellulose and therefore would not 

ingest the hexaflumuron-containing bait. After consumption of hexaflumuron, the termites either 

die in the soil or may be consumed as a small portion of the diet of a limited number of U.S. 

ground-burrowing mammals like the mole. As noted above, swarming termites will not have been 

dosed, and therefore hexaflumuron via these swarmers will not be available to birds. 

The concentration of hexaflumuron in the soil (Clocalsoil) was estimated for European Union 

re-registration of hexaflumuron. This method considers the amount of hexaflumuron which is 

required to eliminate a termite colony and the foraging range of the colony. A large, mature 
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colony will consume an average of 0.5-1 g of hexaflumuron before the colony is eliminated. A 

smaller colony, either due to colony size or termite species, will consume less hexaflumuron 

(approximately 0.1 g) before the colony is eliminated. The termites would die throughout the 

foraging area of the colony. According to the report "Biology of subterranean termites of the 

genus Reticulitermes" by Barbara Thorne, National Pest Control Association, the foraging 

range of Reticulitermes flavipes is 7-79 meters, with an estimated foraging area of 18-2,360 

square meters. The foraging range of the various termite species in Europe is 1-100 m from the 

nest. 

Considering the extremes of foraging area from 2360 m2

 to 1 m2, a soil incorporation of 1 m 

(depth of termites within the soil), a soil density of 1.33 g/cm3, and 1 g of active substance (1 g. 

a.s.) for a large colony and 0.1 g a.s. for a small colony, the concentration of hexaflumuron in 

the soil would range from 0.00032-0.075 mg/kg (ppm). 

Therefore, the Clocalsoil ranges from 0.32-75 μg/kg, however, these results do not account for 

degradation of hexaflumuron in the soil or termites. Alternative methods of calculating soil 

concentration yielded similar values and U.S. soil concentrations would likely be similar. 

EFED Response: 

EFED will consider this information and the estimates provided in the comment above in 

evaluating exposure to hexaflumuron. However, given the Recruit® bait station does not limit 

entry to the bait via slots, it is possible that non-target terrestrial animals and/or predators could 

gain access to the termite bait for these types of applications. According to the label, the 

Recruit® bait station should be placed where termite activity has been observed. Such places 

include in restaurants, grocery stores, bakeries, bottling plants, canneries, meat and poultry 

processing plants and grain mills. Treatment sites may also include 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. The access 

window (the open side) of the bait station allows termites direct access to the bait. The label also 

warns that termites may abandon a station that allows light, air movement, drying of the matrix, 

or invasion by ants or other predators. As such, the same access window that permits access for 

termites may allow honey bees, birds, ants, amphibians, and small mammals to access the bait. 
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4. Bioaccumulation of hexaflumuron in fish 

DAS Comment (p. 23): 

The environmental hazards statement on the label protects against placement of stations in areas 

where the bait could be washed out of the bait cartridge, so exposure of fish to hexaflumuron 

would not occur. On page 6 of the EFED problem formulation document the Agency 

acknowledges that “[hexaflumuron] exposure from runoff from the bait stations should not be an 

issue. Any amount of hexaflumuron that leaches from the bait stations should bind readily to the 

soil”. Furthermore, on page 7, the Agency states “[environmental hazards precautions] reduces, 

if not eliminate, the chances for hexaflumuron to migrate to surface and ground water”. Given 

the lack of hexaflumuron mobility in water and soil, exposure of fish to hexaflumuron is 

extremely remote. 

EFED Response: 

The problem formulation is intended to provide a preliminary understanding of the potential 

environmental fate and ecological effect pathways associated with the current uses of 

hexaflumuron. The discussion on page 8 of the problem formulation focuses on the fate 

properties of hexaflumuron, which indicate that hexaflumuron has the potential to concentrate 

and accumulate in tissue of fish. Discussion of the applicable receptors and routes of exposure 

occurs later in the problem formulation (Section 6), where EFED agrees that the potential for 

transport via surface water runoff, soil erosion, or groundwater is considered low. 

5. Consideration of terrestrial ecosystems 

DAS Comment (p. 24): 

The termite baiting system is not used in terrestrial “ecosystems” but in urban areas around the 

perimeter of termite-infested structures. The Shatter label states in the General Information 

section: “target sites for this system can include buildings, fences, utility poles, decking, 

landscape plantings and trees or other features that could be damaged by termite feeding and 

foraging activity. Shatter can be used on the inside or outside of foundation walls or crawl space 

areas or through concrete and asphalt if adequate soil is not accessible and such action is 

warranted”. Later, in the Monitoring section of the label: “Identify critical areas suitable for 

placing termite stations. Critical areas include locations within or adjacent to visible termite 

activity such as indicated by: foraging tubes, termite infested plants, wood, and other materials; 

and areas conducive to termite foraging (bath traps, moist soil in shaded areas, near irrigation 

sprinkler heads, roof down spouts and other moist areas, and near planting beds or other areas 

with plant root systems”. 
13 of 23

EFED Response: 

Neither the Shatter® nor the Recruit® AG labels limit use of hexaflumuron to urban areas. 

According to EPA’s 2003 Draft Report on the Environment 

(http://www.epa.gov/indicate/roe/pdf/tdEco5-5.pdf), “Urban and suburban ecosystems are areas 

where the majority of the land is devoted to or dominated by buildings, houses, roads, concrete, 

grassy lawns, or other elements of human use and construction.” The report further explains 

“Patches of forest, grassland, shrubland, and wetland in urban/suburban areas provide habitat for 

birds, amphibians, and small mammals.” Therefore, urban, suburban and rural use sites of 

hexaflumuron are considered terrestrial ecosystems and in certain areas of the United States, 

rural and suburban areas make up a significant proportion of the terrestrial ecosystem. 

As stated in the problem formulation, in future ecological risk assessments of hexaflumuron, 

EFED will consider the impact of the use of the baiting systems on nearby “terrestrial 

ecosystems”, as target species (e.g., termites) and non-target species (e.g., birds, mammals, 

amphibians, reptiles and terrestrial insects) can access these areas and potentially be exposed. 

6a. Exposures to non-target insects 

DAS Comment (p. 25): 

The general category of terrestrial insects is quite broad. EFED appears to be concerned with 

pollinators and ground-dwelling insects. DAS addresses both of these groups in detailed 

comments that follow in both Section A and Section B of our EFED Problem Formulation 

comments. Neither pollinators nor ground-dwelling insects are likely to be at-risk due to the 

impregnation of hexaflumuron on the cellulose bait formulation carrier, the specific features of 

the baited termite station delivery system, and the habitat associated with use settings. 

EFED Response:

DAS has not provided sufficient evidence to preclude exposure and subsequent risks of nontarget insects to hexaflumuron. EFED presumes risks to this taxa. In order to alter this 

presumption, DAS must provide sufficient evidence to preclude exposures of non-target insects 

to hexaflumuron (e.g., diameters of holes of bait stations used to house products containing 

hexaflumuron and their relationships to sizes of non-target insects). Additionally, the aboveground use, although not marketed, is still a registered use in order to support this registration the 

data are needed. 

Honey bees are intended to serve as surrogates for beneficial insects such as pollinators and no 

distinctions are made to whether non-target animals are or are not of agricultural significance. 

However, it should be noted that the declining numbers of honey bees has resulted in an 

increasing reliance of native pollinators in agriculture and some of these insects are grounddwelling.
14 of 23

Because there is potential for exposures of non-target insects to hexaflumuron, a field pollinator 

study is necessary to evaluate potential effects of hexaflumuron to non-target insects, including 

pollinators. EFED will consider a larval feeding study with honey bees (Apis mellifera) in place 

of the field pollinator study in order to characterize risks of hexaflumuron to non-target insects. 

The registrant should provide a larval toxicity study protocol for Agency review prior to conduct 

of the study 

6b. Exposures to non-target insects 

DAS Comment (p. 25-26): 

DAS disagrees with the concept that non-termite terrestrial insects will be exposed to residues 

outside the baited termite station by worker termites as developed in several portions of 

comments made to the EFED Problem Formulation. DAS requests that EFED supply the 

references describing the interactions between termites and other terrestrial insects supporting 

this concept, again so that DAS may better respond to potential concerns raised. Ants are 

significant termite predators; however, in hexaflumuron use settings the ant species present are 

likely to be considered household and nuisance pests. In addition, termite colonies have a soldier 

caste which exists to defend the termite colony against attack by predators such as ants. 

EFED Response: 

EFED is concerned with exposures of non-target invertebrates to hexaflumuron through entry 

into the termite stations that contain hexaflumuron. 

6c. Exposures to non-target insects 

DAS Comment (p. 28): 

Shatter termite bait is contained in a bait cartridge which is placed into a termite station during the 

baiting step. The use of sports drinks to wet the bait is to impart enhanced nutritional value to the 

bait for termites. These sports drinks have been shown not to be an attractant to termites but 

instead act as a short-lived phagostimulant and are used to increase the amount of bait 

consumed by termites per unit of time. The rare presence of ants in termite stations is not due to 

the termites or the termite bait but more due to the fact that the stations provide a below-ground 

harborage for nesting. Ants generally forage on seeds, insects, and nectar and have not evolved 

to feed on cellulose. Because of their feeding preferences, ants would not consume the cellulosebased termite bait. Even if the bait was treated with a sugary sports drink and contacted by ants, 

they would suck the sugar from the bait and not actually consume the bait carrier (cellulose) to 

which the hexaflumuron is tightly bound. In addition, these sports drinks become fouled quickly 

when placed in the ground and are thus not a long-term palatable food source for ants. 
15 of 23

EFED Response: 

Ants represent non-target terrestrial insects and can also be pollinators. Some species of nontarget insects consume cellulose. Additionally, other native, ground-dwelling pollinators may 

also be attracted to the bait stations because of the reliance on a sugary attractant. 

DAS has not provided sufficient evidence to preclude exposure and subsequent risks of nontarget insects to hexaflumuron. Therefore, EFED presumes risks to this taxa. In order to alter this 

presumption, DAS must provide sufficient evidence to preclude exposures of non-target insects 

to hexaflumuron (e.g., diameters of holes of bait stations used to house products containing 

hexaflumuron and their relationships to sizes of non-target insects). 

6d. Exposures to non-target insects 

DAS Comment (p. 30): 

Pollinators, such as honey bees, are not able to access the termite bait because it is located 

under ground and is confined within a bait cartridge whose slots are too narrow for honey bees 

to enter. Additionally, honey bees would not use the cellulose-based bait as a food source since 

bees have evolved to process pollen and nectar as food sources. 

EFED Response: 

To clarify the DAS comment, Shatter® is used below ground and Recruit® is used above ground. 

Although DAS indicates that Recruit® AG is not marketed in the United States, because DAS 

maintains a registration, this use will be assessed in future assessments of hexaflumuron. 

The argument that Shatter® bait is located below ground and therefore unlikely to be accessed by 

pollinators applies only to above ground species, such as honey bees. However, there are several 

species of non-target insects, which are also pollinators, such as native bees that dig. Non-target 

insects may be attracted to the bait contained within the Shatter® bait station due to the use of a 

sports drink. Other non-target insects, including some pollinators, may consume cellulose and be 

exposed to hexaflumuron. 

Given the Recruit® bait station does not limit entry to the bait via slots and is located above 

ground, it is possible that non-target terrestrial insects, including honey bees, could gain access 

to the termite bait containing hexaflumuron. Non-target insects may be attracted to the bait 

contained within the Recruit® bait station due to the use of a sports drink. Other non-target 

insects, including some pollinators, may consume cellulose and be exposed to hexaflumuron. 

DAS has not provided sufficient evidence to preclude exposure and subsequent risks of nontarget insects to hexaflumuron. Therefore, EFED will proceed with its evaluation of potential 

risks to this taxa. 
16 of 23

7a. Exposures to mammals, birds, reptiles and amphibians as predators of termites 

DAS Comment (p. 25): 

DAS searched for information on termite predators in North America and found that small 

ground-burrowing mammals were the vertebrate taxa with documented diets including termites 

in foraging habitats associated with hexaflumuron use sites. DAS requests that EFED provide 

the references identifying species of birds, amphibians, and reptiles that consume termites as a 

primary component of their diets so that a further response can be made to these potential 

concerns. 

EFED Response: 

EFED has identified some representative species of terrestrial animals that consume termites. 

These species are listed below. It should be noted that the species listed below are not intended to 

be representative of all species of mammals, birds, reptiles and amphibians inhabiting the U.S. 

and its territories that consume termites, but rather represent examples of such species. 

Mammals: 

o Myrmecophagous species consume ants and termites, which include armadillos1

. 

o The 9-banded armadillo (Dasypus novemcinctus) digs to find its food (McBee and Baker 

1982). Therefore, 9-banded armadillos may be exposed to hexaflumuron through 

consumption of termites which it digs up from the ground. 

Birds: 

o DAS indicated that birds feed on alate stage termites. 

o It is also possible that birds may feed on worker termites that can be visibly located by 

birds (e.g., part of above-ground colonies, present in plants). 

o Example: brewer’s blackbird (Euphagus cyanocephalus)

2

Reptiles: 

o According to E.R. Pianka3, some species of lizards specialize on termites. Pianka states: 

“In North America, the seven most important [prey items of lizards] (totaling 84%), in 

decreasing order by volumetric importance, are: beetles, termites, insect larvae, 

grasshoppers plus crickets, ants, plant materials, and vertebrates.” 

o Several species of reptiles that inhabit California (CA) consume termites, including: the 

CA legless lizard (Anniells pulchra), belding’s orange-throated whiptail lizard 

 

1

 Feldhammer, G.A., Drickhamer, L.C. Vessey, S.H., Merritt, J.F. and C. Krajewski. 2007. Mammalogy: 

adaptation, diversity, ecology. Johns Hopkins University Press. 3rd edition. 2

 Cornell Lab of ornithology. All about birds: Brewer’s blackbird. Accessed online 4 February 2010 at: 

http://www.allaboutbirds.org/guide/Brewers_Blackbird/lifehistory. 

3

 Pianka, E.R. The many dimensions of a lizard’s ecological niche. Accessed online on 22 January 2010 at: 

http://uts.cc.utexas.edu/~varanus/lacertids1.html . 
17 of 23

(Cnemidophorus hyperythrus beldingi), San Diego horned lizards (Phrynosoma 

coronatum blainvillii)

4

 and Sand skinks (Neoseps reynoldsi)

5

. 

Amphibians: 

o Fossorial anurans (e.g., Rhinophrynus dorsalis) are presumed to feed underground, 

feeding on ants, termites and worms.6

 

o The Del norte salamander (Plethodon elongatus), which is located in CA, eats termites.7

Because the example species listed above consume termites, and many of them dig to obtain 

termites, exposures and subsequent risks to mammals, birds, reptiles and amphibians cannot be 

precluded. 

7b. Exposures to mammals, birds, reptiles and amphibians as predators of termites 

DAS Comment (p. 25): 

Non-target terrestrial animals and/or predators are too large to gain access to the termite bait 

directly because they are excluded from the bait by the width of the slots in the bait cartridge. In 

addition, since termites tunnel in the ground and are not exposed outside of the ground unless as 

the swarmer/alate termite caste, the ability of predators to find termites is extremely limited. The 

predator(s) would be confined to those that have evolved to burrow through the ground while 

using termites or insects as a primary food source. This narrows the predatory targets to 

primarily ground-burrowing mammals but these generally make the majority of their diet from 

earthworms. The probability that such ground-burrowing mammals feed extensively on termites 

is remote since they prefer earthworms as their primary diet. 

EFED Response: 

EFED agrees with the DAS statement that “Non-target terrestrial animals and/or predators are 

too large to gain access to the termite bait directly because they are excluded from the bait by the 

width of the slots in the bait cartridge.” Based on this statement, non-target terrestrial mammals, 

birds, reptiles and amphibians are only expected to be exposed to hexaflumuron through 

consumption of contaminated termites. 

EFED does not agree with the statement that “termites tunnel in the ground and are not exposed 

outside of the ground unless as the swarmer/alate termite caste.” According the Ohio State 

 

4

 California department of fish and game. 1994. Amphibian and reptile species of special concern in California. 

Available online at: 

http://www.tamcmonterey.org/programs/bikeped/pdf/carmelhill/eir/FEIR_REFERENCES/CHRT-FEIRSpecies_of_Specal_Concern.pdf 5

 U.S. Fish and Wildlife Services. 2007. South Florida Multi-Species Recovery Plan: Sand Skink (Neoseps 

reynoldsi). Accessed online on 27 January 2010 at: http://www.fws.gov/verobeach/images/pdflibrary/sask.pdf. 6

 Deullman, W.E. and L. Trueb. 1994. Biology of amphibians. Johns Hopkins University Press. 7

 CA department of fish and game. 1994. Amphibian and reptile species of special concern in California. Available 

online at: http://www.tamcmonterey.org/programs/bikeped/pdf/carmelhill/eir/FEIR_REFERENCES/CHRT-FEIRSpecies_of_Specal_Concern.pdf
18 of 23

University Extension8

, subterranean termites can sometimes form colonies above ground in 

locations with sufficient moisture. Therefore, non-target terrestrial animals (i.e., mammals, birds, 

reptiles and amphibians) may consume termites above ground that are not in the alate caste (i.e.,

worker caste). In addition, the Shatter® label states that the user should: “Identify critical areas 

suitable for placing termite stations. Critical areas include locations within or adjacent to visible 

termite activity such as indicated by: foraging tubes, termite infested plants, wood, and other 

materials; and areas conducive to termite foraging (bath traps, moist soil in shaded areas, near 

irrigation sprinkler heads, roof down spouts and other moist areas, and near planting beds or 

other areas with plant root systems”. If it is possible for the pesticide user to locate “visible 

termite activity”, then it is also possible for termite predators to capture those termites above 

ground. 

7c. Exposures to mammals, birds, reptiles and amphibians as predators of termites 

DAS Comment (p. 25): 

As mentioned above, termites have a swarmer/alate caste which exists to start new termite 

colonies through king & queen pair finding, mating, and colony establishment. In the U.S., birds 

feed on termites when they swarm from their nest in the ground. These flying termites known as 

swarmers or alates cannot be a vehicle for transporting hexaflumuron from the baited termite 

station to predators such as birds because if hexaflumuron were present in the termites they 

would have died while trying to molt to the alate or swarmer stage, thereby eliminating this caste 

from the termite colony. 

EFED Response: 

As mentioned above, EFED does not agree with this comment. It is possible that termites of all 

castes may carry a body burden of hexaflumuron that is not sufficient to prevent molting and 

progression to the final life stages. In order to evaluate this statement, it is necessary to 

understand the minimum hexaflumuron dose that is efficacious in termites. However, the 

proposed steady-state concentration of 107 mg hexaflumuron/kg termite (calculated using MRID 

45516725) that would be used to represent the concentration of hexaflumuron in worker termites 

resulting from consumption of contaminated briquettes is efficacious (based on the results of the 

study) and is likely conservative of levels that are not efficacious. 

7d. Exposures to mammals, birds, reptiles and amphibians as predators of termites 

DAS Comment (p. 26-27): 

DAS suggests this analysis for Chronic Risk to Ground-Burrowing Mammal Termite Predators: 

 

8

 Suiter, D.R., Jones, S.C. and B.T. Forschler. Biology of subterranean termites in the Eastern United States. Ohio 

State University Extension. Bulletin 1209. Accessed online on 27 January 2010 at: http://ohioline.osu.edu/b1209/. 
19 of 23

The USEPA Wildlife Exposure Factors Handbook (1) provides information on three 

representative insectivorous vertebrate predators, the American woodcock, marsh wren, and 

short-tailed shrew. The two birds generally forage in woodlands and marshes and therefore are 

likely not exposed to hexaflumuron use sites. However, the short-tailed shrew forages in most 

habitat types and is common in areas with abundant vegetative cover, including habitat that 

could have hexaflumuron containing baited termite stations. 

The short-tailed shrew can be considered a representative worst case surrogate for vertebrate 

termite predation, and a risk quotient can be calculated for chronic risk. 

Body weight (g) 15 

Food ingestion rate (g/day) 7.95 

Termite dietary composition a (% volume) 8.1 

Hexaflumuron concentration b (mg/kg) 107 

Therefore Daily dose (mg/kg/day) c = 4.6 

Chronic endpoint (mg/kg/day) d 5 

Therefore Risk Quotient (RQ) = 0.92 

a "misc. animals" (see Handbook page 2-214) 

b MRID 45516725 

c Conc. (mg hexaflumuron /kg termite) * (1 kg termite/1000 g termite) * Food ingestion 

rate g/day * Termite dietary composition % / 100 / g bw * (1000 g bw/1 kg bw) 

d MRID 44233003 

In this example, the RQ of 0.92 is less than the Agency’s Level of Concern of 1 for all nonendangered and endangered animals. Note that the magnitude of exposure is very conservative 

in the calculation, which assumes that all of the miscellaneous animals consumed are termites 

and all termites consumed come from a colony recruited to foraging at baited termite stations 

containing hexaflumuron. As discussed below, residues in soil that could be ingested by 

earthworms or other soil-dwelling prey of small mammals are expected to be significantly lower 

than those in worker termites. 

EFED Response: 

EFED appreciates the above analysis of the potential chronic risks to mammals. Because there is 

potential for exposure of non-target mammals to hexaflumuron, EFED’s approach for estimating 

exposures of hexaflumuron to mammals, as well as birds, reptiles and terrestrial-phase 

amphibians will assume diets of 100% termites, which is in contrast to the DAS approach 

described above where the diet of the short-tailed shrew was assumed to be 8.1% termites. 
20 of 23

8. Exposures to terrestrial plants 

DAS Comment (p. 36): 

Hexaflumuron was initially developed for use on agricultural crops in Europe, therefore data 

are available to demonstrate the lack of crop injury. However, non-target plants will not be 

exposed to hexaflumuron when used in the termite baiting system. 

Hexaflumuron applied at rates up to 100 g ai/ha resulted in no injury to any of the evaluated 

plants from eight crop species and 10 weed species from nine plant families (3). It is therefore 

concluded that pre-emergence applications of hexaflumuron would have no significant long term 

adverse impact on the growth and development of plants. 

Hexaflumuron has a mode of action that inhibits chitin synthesis in insects. Since it is not an 

herbicide and does not have a mode of action applicable to plants, there will be no effects on 

plant seedling emergence. In addition, termites do not transport bait from the baited termite 

station containing the bait cartridge but only move bait that has actually been consumed by the 

termite itself. The hexaflumuron is inside the termite and is not exposed to the environment. 

EFED Response: 

DAS has not provided sufficient information to preclude exposure of terrestrial plants to 

hexaflumuron. If DAS submits the plant toxicity study that is described in the comment, it will 

be evaluated by EFED. 

9. Metabolism and Toxicity in Mammals 

DAS Comment (p. 39-40): 

Hexaflumuron has very low acute toxicity by the oral, dermal, inhalation and intraperitoneal 

routes of administration (14). The data from subacute and chronic toxicity studies in rats, mice, 

and dogs identified the liver and haematropoeitic systems as the target organs. The toxicities 

observed for hexaflumuron were mild effects. The NOEL for hexaflumuron in rats and mice for 

13 weeks were determined to be 25 and 5 mg/kg body weight/day, respectively (14). The results 

from chronic toxicity and carcinogenicity studies in rats and mice identified the liver as the 

target organ. The NOEL for hexaflumuron in rats and mice from chronic dietary exposures were 

determined to be 75 and 25 mg/kg body weight/day, respectively. In an oral multigenerational 

reproduction study with hexaflumuron in rats (MRID 44233003) it was concluded that the 

overall no adverse effect level of hexaflumuron is 5 mg/kg body weight/day. 

In the carcinogenicity studies with rats and mice fed hexaflumuron, there were no increases in 

the incidence of tumors of any type. No tumorigenic potential was demonstrated. 

Pharmacokinetics and metabolic studies have been completed in rats and mice to assist the 

interpretation of toxicity study results and species differences. The fate of hexaflumuron given at 
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5 or 250 mg/kg body weight in these species is similar. Disposition studies of orally administered 

hexaflumuron show that the relationship between administered dose and kinetics is non-linear. 

At 5 mg/kg body weight the majority of administered hexaflumuron was absorbed (14). It was 

clear that increasing the dose beyond about 25 mg/kg body weight did not produce a 

commensurate increase in systemic dose. This explains the modest increase in toxicity observed 

with large increases in the dose. Approximately 15-20% of the dose was excreted as parent. The 

principle metabolite in the benzoyl ring was mostly excreted in the urine. Approximately 50% of 

the aniline-ring metabolites were excreted in the urine or feces. 

In the two generation rat reproduction study, hexaflumuron treatment had no effect on fertility, 

reproductive performance, or fetal development. The NOEL of the two generation reproduction 

study was determined to be 125 mg/kg body weight/day (14). 

In conclusion, hexaflumuron poses very low hazard to ground-burrowing mammals that may 

consume small amounts of termites containing hexaflumuron. 

EFED Response: 

Because mammalian species consume termites, exposures and subsequent risks to mammals, 

cannot be precluded. However, after the cited studies have been reviewed by HED, those 

deemed acceptable will be used by EFED to further characterize potential risks. 

10. Efficacy and Mode of Action 

DAS Comment (p. 38): 

Hexaflumuron is effective at eliminating a termite colony because the colony’s worker caste is 

constantly searching for new food sources. Once worker termites locate the untreated wood 

monitoring devices, and it is subsequently replaced with Shatter® termite bait containing 

hexaflumuron, the “dosed” termites take the hexaflumuron back to the colony. The hexaflumuron 

is efficiently passed through trophallaxis from one termite to another in the colony. As with other 

insect growth regulator insecticides, time to termite mortality is not dose dependent, i.e. termites 

that consume more hexaflumuron do not die faster than those who consume less. The termites 

that have received a dose of hexaflumuron are prevented from molting. In any one treated 

colony, enough of the worker caste dies such that the colony can no longer survive due to poor 

health. The result is death of the remainder of the colony even though the remainder has not 

received any dose of hexaflumuron. Furthermore, since hexaflumuron prevents molting, termites 

that have received a dose of hexaflumuron cannot develop to the swarmer/alate stage, and 

therefore cannot leave the nest to swarm. 

The mode of action for hexaflumuron is as an insect growth regulator. Specifically, 

hexaflumuron acts by disrupting chitin deposition in the insect cuticle. Normally this occurs after 

ingestion of the material with death occurring during molting (ecdysis) to the next developmental 

stage. 
22 of 23

EFED Response: 

EFED appreciates the detailed explanation of hexaflumuron’s mode of action and its intended 

effect on the termite colony as a whole. As noted above, it is possible that termites of all castes 

may carry a body burden of hexaflumuron that is not sufficient to prevent molting and 

progression to the final life states. In order to evaluate this statement, it is necessary to 

understand the minimum hexaflumuron dose that is efficacious in preventing ecdysis in termites. 

11. Conceptual Diagram 

DAS Comment (p. 44): 

First, the exposure to birds would be negligible because birds would not consume subterranean 

termites, and as discussed above, the swarming alate termites would not contain hexaflumuron. 

Similarly, amphibians and reptiles will not seek the hexaflumuron-containing cellulose bait as a 

food source, yet may opportunistically find habitat protection within a termite station and 

perhaps consume a termite. 

Secondly, the data previously presented demonstrates that there is no hazard to birds and 

mammals. In other words, data are available to prove that there will be no attribute change to 

birds and mammals: survival, growth, and reproduction are unaffected by hexaflumuron. 

Due to the use pattern, hexaflumuron will not pose an ecological risk because it cannot reach 

ecological receptors in biologically significant concentrations, as calculated in Section V. A, 

above. Note that the calculations overestimate the exposure, since it in unlikely that an animal 

would consume treated termites every day. Lower values would likely be obtained for reptiles 

and amphibians, since they rarely consume termites. Furthermore, animals which prey on 

shrews and other animals that may consume hexaflumuron-treated termites would likewise be 

exposed to a very low concentration of hexaflumuron that would pose minimal risk. 

Therefore, there would be minimal risk to mammals, amphibians, and reptiles which may 

directly or indirectly consume hexaflumuron via termites. 

EFED Response: 

As indicated above, EFED has identified representative species of mammals, reptiles and 

amphibians that consume termites. DAS indicated that birds feed on alate stage termites. It is 

also possible though that birds may feed on worker termites while they are above ground (e.g., in 

plants) as well. Therefore, because there is potential for exposures of mammals, birds, reptiles 

and terrestrial-phase amphibians to hexaflumuron (through consumption of contaminated 

termites) toxicity data are necessary to quantify the acute and chronic effects of hexaflumuron to 

these taxa. DAS has not provided sufficient evidence to preclude exposure and subsequent risks 

of non-target insects to hexaflumuron. Therefore, EFED is requesting data to determine relevant 

effect levels for these taxa. 
23 of 23

Because of the potential exposures of these taxa to hexaflumuron, EFED does not agree with 

DAS’s proposed revisions to the conceptual model. Based on available information, EFED will 

conduct ecological and endangered species assessments of hexaflumuron using the conceptual 

model that is provided in the problem formulation. 

12. Risk Hypothesis 

DAS Comment (p. 44-45):

As the Agency describes in Section 6.1 (beginning on Page 12 of 34) of the Problem 

Formulation, a risk hypothesis described the predicted relationship among the stressor, 

exposure, and assessment endpoint response, along with the rationale for their selection. 

For hexaflumuron, DAS proposes the following revised ecological risk assessment: 

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

does NOT have the potential to affect non-target terrestrial animals including birds, mammals, 

amphibians, reptiles, and terrestrial insects when used in accordance with the product labeling. 

Likewise, federally-listed threatened and endangered species as well as non-listed species would 

be unaffected. 

EFED Response: 

As indicated above, EFED has identified representative species of mammals, reptiles and 

terrestrial-phase amphibians that consume termites. DAS indicated that birds feed on alate stage 

termites. It is also possible that birds may feed on worker termites that are above ground (e.g., in 

plants). Therefore, because there is potential for exposures of mammals, birds, reptiles and 

amphibians to hexaflumuron (through consumption of contaminated termites) toxicity data are 

necessary to quantify the acute and chronic effects of hexaflumuron to these taxa. DAS has not 

provided sufficient evidence to preclude exposure and subsequent risks of non-target insects to 

hexaflumuron. Therefore, EFED is recommending that effects data are submitted for these taxa. 

Because of the potential exposures of these taxa to hexaflumuron, EFED does not agree with 

DAS’s proposed risk hypothesis. Based on available information, EFED will conduct ecological 

and endangered species assessments of hexaflumuron using the risk hypothesis that is stated in 

the problem formulation.