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### MEMORA DUM February 17,2010

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

E li za beth Beh l, Chief

Environmental Risk Branch 4

Environmental Fate and Effects Division

Office of Pesticide P rograms Chuck Peck Environmental Enginee

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Kristina Garber

, Biologist

Environmental Risk Branch 4 

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.- ........- Russell a em
, Chemical Review Manager

Thomas Moriarty

, Team Leader Rereg istration Bran ch

Pe sticide R eregi stration D ivision

Office of Pesticide Pro grams

F rom:

Through: To :

Ba sed on commen ts rece ived and EFED 's r esponses (con tained in this memo)

, EFE D h as r evised

it s pr eliminary prob lem formu lation. Th is rev ised pro blem fo rmulation is a ttached.

1 0f 232 of 23 1. DAS reports referenced in commen ts are available to the Agency

DAS Comment (p. 36):

Please note that all reports referenced within this [DAS’s comment] docu ment are available to the Agency upon request.

EFED Response:

DAS references several studies that may be rele vant to fulfill data gaps identified in EFED’s problem formulation, including: acute oral toxicity of hexa flumuron to honey bees (nonguideline), avian reproduction (guideline 850.2300) and terrestr ial plant toxic ity (guideline 850.4100). EFED requests that DAS provide the studies listed below (that were referenced in DAS’ comments) so that they may be evaluate d by EFED. If these st udies 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 hone y bees, avian reproduction and terrestrial plant toxicity) accu rately represent current data ga ps; EFED is not modifying these requests at this time.

Cole, J. H. The Acute Contact and Oral Toxicity To Hone y 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 Unpublished report of Dow AgroSciences DET 645, 02-SEP-1985.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 Bobw hite Quail. Unpublis hed 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 Mall ard 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 Unpublished report of Dow AgroSciences GHE-T-192, 10 October 1988.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 aqua tic toxicity studies that have not been received by the Agency. These studies may provide information on the acute toxicity of hexaflumur on to estuarine/marine invertebrates, chronic toxicity to freshwater inve rtebrates 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 T oxicity 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 1988.3 of 23 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-contai ning bait is used in a termite baiting system. First, hexaflumuron, which is formulated in a term ite bait (Shatter, Recr uit AG), is used to protect residential, commercial , and historical structures fr om wood-destroying subterranean

termites. Recruit AG and Shatter contain a cellulose-based bait fo rmulation (bait matrix) with the active ingredient hexaflumuron, both of whic h 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. Th e bait matrix base is cellulose compressed into dry oblong briquettes approximatel y 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 essentiall y no dust, dramatically reduci ng the potential for inhalation exposure. In-ground uses of Shatter utilize a device that consists of a ri gid plastic tube with termite access slots covering the su rface 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 comme rcial 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 devi ces out of the termite stations); or alternatively, monitoring

devices can be an electroni c version called ESP which has the two pieces of wood held together by glue spots alone or by glue spots and brads. A ccording to the directions for use, placement of termites into the Shatter bait cartridge is optio nal 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 manageme nt 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 termit e stations are installe d around a termite-infested structure as specified in the labeling. After the indication of termite fe eding is observed on the4 of 23 untreated wooden monitoring device, the cap of th e 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 bri quettes containing 0.5% hexaflumuron (250-275 mg hexaflumuron per bait cartridge). Each bait ca rtridge is encased in plastic shrink-wrap packaging that protects the bait ma trix 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 th e bait cartridge, the pl astic shrink-wrap is removed, and the bait cartridge is placed into the in-ground termite stati on 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 duri ng 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 stati on for Recruit AG) is applied only when and where termite activity has been detecte d. At any one site, the majority of the termite stations contain untreated wood (monitoring devices), for monitori ng purposes. In a “worst-case” scenario, four adjacent homes each with a 1⁄4 acre property coul d be infested with a termite colony, and be treated simultaneously with Shatter termite bai t. Of the approximatel y 100 below-ground termite stations, during a typical year approximately 12-16 termite stations would contain hexaflumuron bait while the remainder would contain only untreat ed 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 cart ridges were sold to pest man agement professionals per year.

After termite colony elimination, or any time wh en termites cease feed ing on the bait, the bait cartridge is removed and disposed of according to label directions.

EFED Response:

EFED will revise the problem fo rmulation 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 exposu re 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 cons ider more detail ed 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 cartridg e 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 relev ant to amount of bait. However, the Shatter5 of 23 bait cartridge itself does have an af fixed label that discloses the amount of bait in the cartridge. In addition, the Recruit AG (above-ground) station itself does have an affi xed label on it that discloses the amount of bait in this station. The maximum numbe r of in-ground termite stations on an area is determined by the perimeter linear f eet of the structure being attacked by termites. Termite stations are placed in the ground around th e perimeter of the stru cture 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 whic h is commercially used in the marketplace. DAS has over 15 years of use exp erience with termite baiting syst ems. The following scenarios represent use patterns based on DAS’ market expe rience. A Shatter bait cartridge contains 50 to 55 grams of the 0.5% hexaflumuro n bait. On average, 3 to 4 ba it cartridges are used at a termite-infested structure duri ng 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 w ould be one bait cartridge per structure.

High-density home example: one a verage-sized home has about 225 li ner 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 struct ures 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” fo r all four homes. From use exp erience, approximately 12 to 16% of the installed termite stations will be hi t by termites. This translates to 12 to 16 bait cartridges used per acre to tr eat 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 stati ons should be installed would be useful for

homeowners if available on the label. Given th e current label language, a licensed applicator is not restricted on the maximum amount of product th at 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 perimete r 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 replacemen t of the Shatter termite bait cartridge when the material in the bait cartridge is nearly or totally consumed.

EFED will consider the historical use informati on and estimates provided in the comment above in evaluating exposure of non-target organism s to hexaflumuron. DAS should consider more6 of 23 detailed labeling in order to further reduce the potential scope of the assessment and associated

uncertainties.

Even though the above ground product is not curre ntly being marketed, the Agency must evaluate the use pattern to en sure 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 T itle: Aerobic Soil Metabolism • Guideline Number: 835.4200; Study T itle: Anaerobic Soil Metabolism • Guideline Number: 835.1230/1240; Study Title: Leaching/Mobility Study • Guideline Number: 850.2300; Study T itle: Avian Reproduction Tests • Guideline Number: Non-guideline; Study Titl e: Acute oral toxicity to honey bees • Guideline Number: 850.3040; Study Titl e: Field Testing for pollinators • Guideline Number: 850.4100; Study Title: Terr estrial Plant Toxicity Test, Tier 1

Hexaflumuron cannot be classified as readily biodegradable (4). In aero bic soils, hexaflumuron first-order degradation half-life values ranged fr om 108-255 days (5). In this study, two aerobic soil metabolism products we re identified from the 14 C-aniline-labeled h exaflumuron. The two corresponding compounds resulting from the 14 C-benzoyl-labeled hexaflumuron were presumed to be transient and quickly degraded to 14 CO 2 . The identity of the amine degradate was confirmed by GC-MS. The urea degradate never exceeded 11% Applied R adioactivity (AR) in any soil, while the amine degradate reached a ma ximum of 20% AR at 120 days after treatment (DAT) in one soil before declining. Another unkno wn, 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 radioac tivity 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 followi ng aerobic soil degrada tion of aniline-labeled noviflumuron, which is similar to hexaflumuron (m olecular weight of 529.15, +1C, +3F, -H) (6).

In general, in the 14 C-benzoyl-labeled samples the amount of 14 CO 2 approached 17-24% of applied radioactivity after 1 year. Since the amount of applied radioactivity in the volatile traps did not increase appreciably, especially af ter 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 14 CO 2 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 overco me inefficient trapping of volatile CO 2 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).7 of 23 Bound radioactive residues increa sed 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 14 CO 2 , and material balance was 88.8-103% AR at 365 DAT (6) fu rther supporting the conclusi on that insufficient trapping was the cause of the lower hexaflumuron mass balances.

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

CO 2 . These metabolites would not accumulate in the environment. The amine and urea degradates from the aniline portion of hexaflumur on 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 K d 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 K d values for the noviflumuron urea and amine metabolit es were 19.5 and 39.0 mL/g, respectively, with corresponding K OC values of 2,478 and 3,983 mL/g.

A study to determine the anaerobic soil metabo lism should not be required since exposure of hexaflumuron in the termite bait system is unli kely to be exposed to anaerobic soil conditions. However, information is available to demonstr ate that hexaflumuron degraded more rapidly

under anaerobic conditions than under aerobic conditi ons (5) with a half-life of 40-72 days. The low mass balance can reasonably be attributed to insufficient 14 CO 2 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 wo uld have been achieved with a higher NaOH concentration, but that the re maining results including hal f-life would not differ.

Results indicate that hexaflumuron will be moderately persistent in soil under aerobic conditions, but due to the formul ation of this highly-sorbed co mpound in a cellulose bait matrix enclosed in a protected, in-ground plastic termite station, it is unlikely th at 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 supple mental. 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 id entified; and, (2) a low material balance (up to 55% of the applied ra dioactivity was not accounted for by the termination of the study) in the benzoyl-labeled portion of the st udy 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 Ha nford sandy loam). In both tests, the amounts captured in the volatile tr aps in the supplemental study were significantly higher than the amounts captured in the initia l 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 that8 of 23 the “M8 is a result of poor chromatography” does not appear to be consis tent with data showing that M8 appears in several TLC systems/soil analyses (TLC sy stem 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 be nzoyl-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 th e supplemental study using a higher concentration of NaOH in the volatile trap did show a s light improvement, but did not provide an acceptable material balance. In th e Hanford sandy loam soil, the overall material

balance increased from 40.43% to 54.43% of the radi oactivity at 60 days. In the Castle Rising sandy loam soil, the overall material bala nce increased from 72.6 % to 74.29% of the radioactivity at 60 days . As such, the anaerobic soil metabol ism study will remain classified as supplemental and the data require ment 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 835.41 00 (Aerobic Soil Metabolism) and 835.4200 (Anaerobic Soil Metabolism).

3b. Fate of hexaflumuron in the environment

DAS comment regarding need for additi onal 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 hexaflu muron will be strongly sorbed and immobile. The un-aged leaching in four soils (2 US and 2 EU) in duplicate (one replicat e per radiolabeled test substance) was originally reported by Y on 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 leac h in four agricultural soils.” Hexaflumuron remained in the top 5 cm of soil. The report further concluded that hexa flumuron was not degraded in the soil. Also, the aerobic soil metabolism study (5) calcul ated apparent KOC values of 5338-70977 mg/L. Therefore, the immobility of hexaflumuron is cl early characterized wit hout need for further
testing.

A batch equilibrium adsorption and desorp tion study was conducted with the analog noviflumuron. At four dose concentrations ranging from 0.010 to 0.097 mg/L, noviflumuron adsorption K d values were greater than 850 mL/g and K OC values were greater than 32,000 mL/g (8). In this study, Dow adsorption K f values ranged from 557 to 5,840 mL/g, averaging 2,280 mL/g. The data reported by Racke (7) would indica te 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 and9 of 23 as a sorption matrix for hexaflumuron. In the e vent of flooding of a term ite station containing hexaflumuron-formulated cellulose bait matrix, a small percentage (<0.025%) of the formulated material may move out of the baite d termite station. However, the presence of soil will mitigate any movement of hexaflumuron into the surr ounding environment; le ss than 0.000053% of the hexaflumuron in the cellulose bait matrix was de tected 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 E FED 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 qualitativel y determined that hexaflumuron was relatively immobile. The un-aged leaching portion of the mobility/leaching study was found to partially satisfy the data re quirements by providing mobility data for the unaged parent. Hexaflumuron was not considered m obile in silt loam, clay loam, and two sandy loam soils. However, the aerobically-aged mob ility 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 dete rmine the amount released from the soil to the solution (desorbed). In the aged mobility experiment described in this study, 14 C-labeled

hexaflumuron was incubated in four soils under aerobic conditions for 30 days; the 14 C residues were then extracted from the soils by shaking th ree 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 equilibr ations as "desorption." The soils were then further extracted with acetone and sodium hydroxide to determine the am ount "adsorbed" to the soil. The registrant

then calculated “K d ” 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 (K des ), 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 de sorbed. No inferences could be made concerning adsorption coefficients (K ads ) of the degradates, since adsorption of the degradates could not be separated from ot her 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 -CF 3 attached to the end,

as well as an additional fluorine on the ani line ring. In the aforementioned study (MRID 45516709), the test material was uniformly labeled on the aniline ring. It is unclear what effect10 of 23 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 th at leaching from an actual bait station during “flooding” conditions would most likely be minimal and that hexaflumuron does not appear to migrate thr ough 1 inch of soil (<0.000 06% through 25 mm of soil). It should be noted, t hough, that only one soil type (Charent illy) was used in the analyses

and it was unclear if that soil t ype is adequately repr esentative of soil co nditions found in all of the areas in United States where the product may be used.

Given the deficiencies noted above, EFED cons iders the lack of an acceptable leaching and adsorption/desorption study as a data gap. However, EFED also agrees th at hexaflumuron is not likely to be mobile in soils. Estimates from EPISuite (K OC =7272), as well as the qualitative information provided in the flood study (MRID 47806601), indicate that he xaflumuron will not easily migrate in soil. As such, EFED has ag reed 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 hexaflumuro n, such as the low water solubility and strong adsorption to soil, will prevent movement of hexa flumuron out of the baited termite stations. In addition, hexaflumuron that remains associated w ith 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 Sh atter in-ground bait cart ridges 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 enclose d, sturdy mud tunnels rather than becoming exposed above ground. Therefore, th e dosed termites will not be readily exposed and available as a food source to predators.

Other ground-burrowing mammalian predators are eith er 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 c onsumption 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 c onsiders the amount of hexaflumuron which is required to eliminate a termite colony and the foraging range of the colony. A large, mature11 of 23 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 th e colony is eliminated. The te rmites would di e throughout the foraging area of the colony. According to the report "Biology of subterranean termites of the genus Reticulitermes" by Barbara Thorne, Na tional Pest Control Association, the foraging range of Reticulitermes flavipes is 7-79 mete rs, with an estimated foraging area of 18-2,360 square meters. The foraging range of the various te rmite species in Europe is 1-100 m from the

nest.

Considering the extremes of foraging area from 2360 m 2 to 1 m 2 , a soil incorporation of 1 m (depth of termites within the soil), a soil density of 1.33 g/cm 3 , and 1 g of active substance (1 g. a.s.) for a large colony and 0.1 g a.s. for a sma ll 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 μ g/kg, however, these resu lts do not account for degradation of hexaflumuron in the soil or term ites. Alternative methods of calculating soil concentration yielded similar va lues 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 hexaflumuro n. However, given the Recruit ® bait station does not limit entry to the bait via slots, it is possible that non- target terrestrial animal s 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 term ite activity has been observed. Such places include in restaurants, grocer y stores, bakeries, bottling plan ts, 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 term ite foraging and feeding activity. The access window (the open side) of the bait st ation allows termites di rect access to the ba it. The label also warns that termites may abandon a station that al lows light, air movement, drying of the matrix, or invasion by ants or other predators. As su ch, the same access window that permits access for termites may allow honey bees, birds, ants, am phibians, and small mamm als to access the bait.12 of 23 4. Bioaccumulation of hexaflumuron in fish

DAS Comment (p. 23) :

The environmental hazards statement on the label pr otects against placement of stations in areas where the bait could be washed out of the bait ca rtridge, 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 ba it stations should not be an issue. Any amount of hexaflumuron that leaches from the bait stat ions 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 provi de a preliminary understanding of the potential environmental fate and ecological effect path ways 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 terre strial “ecosystems” but in urban areas around the perimeter of termite-infested structures. The S hatter label states in the General Information section: “target sites for this system can incl ude buildings, fences, u tility 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 lo cations within or adjacent to visible termite activity such as indicate d by: foraging tubes, termite infest ed plants, wood, and other materials; and areas conducive to termite fora ging (bath traps, moist soil in s haded areas, near irrigation sprinkler heads, roof down spouts and other moist ar eas, 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/indi cate/roe/pdf/tdEco5-5.pdf ), “Urban and suburba n 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 us e and construction.” The report further explains “Patches of forest, grassland, shrubland, and we tland in urban/suburban ar eas provide habitat for birds, amphibians, and small mammals.” Ther efore, urban, suburban and rural use sites of hexaflumuron are considered terrestrial ecosyst ems and in certain areas of the United States, rural and suburban areas make up a significan t proportion of the terrestrial ecosystem.

As stated in the problem formul ation, 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 addr esses both of these groups in detailed comments that follow in both Section A and S ection B of our EFED Problem Formulation comments. Neither pollinators nor ground-dwelling insects are likel y to be at-risk due to the impregnation of hexaflumuron on th e cellulose bait formulation carrier, the specific features of

the baited termite station deliv ery system, and the habitat asso ciated 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 us ed 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 fo r beneficial insects such as pollinators and no distinctions are made to whether non-target animal s are or are not of agri cultural significance. However, it should be noted that the declini ng numbers of honey bees has resulted in an increasing reliance of native polli nators in agriculture and so me of these insects are grounddwelling.14 of 23 Because there is potential for e xposures 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 larv al feeding study with honey bees ( Apis mellifera ) in place of the field pollinator study in order to characteri ze risks of hexaflumuron to non-target insects. The registrant should provide a la rval 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 te rrestrial 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 Formul ation. DAS requests that EFED supply the references describing the interact ions between termites and other terrestrial insects supporting this concept, again so that DA S may better respond to potentia l concerns raised. Ants are significant termite predators; however, in hexafl umuron use settings the ant species present are likely to be considered househol d and nuisance pests. In addition, te rmite 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-targ et invertebrates to hexaflumuron through entry

into the termite stations th at 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 pr esence of ants in termite stations is not due to

the termites or the termite bait but more due to the fact that th e 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 act ually 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 terres trial insects and can also be pollinators. Some species of nontarget insects consume cellulose. Additionall y, 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 pres umes 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 cartri dge whose slots are too narrow for honey bees to enter. Additionally, honey bees would not use the cellulose-bas ed 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 assess ed in future assessments of hexaflumuron.

The argument that Shatter ® bait is located belo w ground and therefore unli kely to be accessed by pollinators applies only to above ground species, such as honey bees. However, there are several species of non-target insects, whic h 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-tar get terrestrial insects, includ ing honey bees, could gain access to the termite bait containing he xaflumuron. 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 consum e 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 diet s including termites in foraging habitats associated with hexaflumuron use sites. DA S requests that EFED provide the references identifying species of birds, amph ibians, and reptiles that consume termites as a primary component of their diets so that a furt her 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, bird s, reptiles and amphibi ans 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 armadillos 1

.

o The 9-banded armadillo ( Dasypus novemcinctus ) digs to find its food (McBee and Baker 1982). Therefore, 9-banded armadillos ma y 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 wo rker 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. Pianka 3 , 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, pl ant 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. 3 rd 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. A ccessed 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 consum e termites, and many of them dig to obtain termites, exposures and subsequent risks to ma mmals, 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 narro ws the predatory targets to primarily ground-burrowing mammals but these generally make the ma jority of their diet from earthworms. The probability that such ground-bu rrowing 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-ta rget terrestrial animals and/or predators are too large to gain access to the termite bait direc tly because they are excluded from the bait by the

width of the slots in th e bait cartridge.” Based on this statem ent, non-target terrestrial mammals, birds, reptiles and amphibians are only expect ed to be exposed to hexaflumuron through consumption of contaminated termites.

EFED does not agree with the statement that “t ermites tunnel in the ground and are not exposed outside of the ground unless as the swarmer/alat e 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 Fl orida Multi-Species Recovery Plan: Sand Skink ( Neoseps reynoldsi ). Accessed online on 27 January 2010 at: http://w ww.fws.gov/verobeach/imag es/pdflibrary/sask.pdf.

6 Deullman, W.E. and L. Trueb. 1994. Biology of amphibians. Johns Hopk ins University Press.

7 CA department of fish and game. 1994. Amphibian and re ptile species of special concern in California. Available online at: http://www.tamcmonterey.org/programs/bi keped/pdf/carmelhill/eir/FEIR_REFERENCES/CHRT-FEIRSpecies_of_Specal _Concern.pdf18 of 23 University Extension 8 , subterranean termites can sometimes form colonies above ground in

locations with sufficient moisture. Ther efore, non-target terrestrial animals (i.e ., mammals, birds, reptiles and amphibians) may consume termites a bove ground that are no t in the alate caste (i.e., worker caste). In addition, the Shatter ® label states that the user s hould: “Identify critical areas suitable for placing termite stations. Critical areas include locations within or adjacent to visible termite activity such as indicated by: foraging t ubes, termite infested plants, wood, and other materials; and areas conduc ive 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 system s”. 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/alat e caste which exists to start new termite colonies through king & queen pai r finding, mating, and colony esta blishment. 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 tr ansporting 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 th at 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 he xaflumuron/kg termite (calculated using MRID 45516725) that would be used to represent the con centration of hexaflumuron in worker termites resulting from consumption of contaminated briq uettes 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. an d 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 H andbook (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. Ho wever, the short-tailed shrew forages in most habitat types and is common in areas with abundant veg etative cover, including habitat that could have hexaflumuron contai ning baited termite stations.

The short-tailed shrew can be considered a re presentative worst case surrogate for vertebrate termite predation, and a risk quotient can be calcul ated for chronic risk.

Body weight (g) 15 Food ingestion rate (g/day) 7.95 Termite dietary composi tion 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 term ite) * Food ingestion rate g/day * Termite dietar y composition % / 100 / g bw * (1000 g bw/1 kg bw)

d MRID 44233003

In this example, the RQ of 0.92 is less than th e Agency’s Level of Concern of 1 for all nonendangered and endangered animals. Note that the m agnitude 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 recr uited to foraging at baited termite stations containing hexaflumuron. As discussed below, re sidues in soil that c ould 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 pote ntial chronic risks to mammals. Because there is potential for exposure of non-targ et mammals to hexaflumuron, EFED’s approach for estimating exposures of hexaflumuron to mammals, as well as birds, re ptiles 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-ta iled 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 inju ry to any of the evaluated plants from eight crop species and 10 weed species fr om nine plant families (3). It is therefore concluded that pre-emergence app lications 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 applic able to plants, there will be no effects on plant seedling emergence. In addition, termites do not transport bait fr om the baited termite station containing the bait cartridge but only move bait that has ac tually 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 te rrestrial plants to

hexaflumuron. If DAS submits the plant toxicity study that is de scribed 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 th e oral, dermal, inhalation and intraperitoneal routes of administration (14). The data from su bacute and chronic toxicity studies in rats, mice, and dogs identified the liver and haematropoeitic sy stems 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 hexa flumuron in rats and mice from ch ronic dietary exposures were determined to be 75 and 25 mg/kg body weight/day , respectively. In an oral multigenerational reproduction study with hexaflumuron in ra ts (MRID 44233003) it was concluded that the overall no adverse effect level of hexa flumuron is 5 mg/kg body weight/day.

In the carcinogenicity studies with rats and mi ce 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 at21 of 23 5 or 250 mg/kg body weight in thes e species is similar. Disposition studies of orally administered hexaflumuron show that the relationship betw een administered dose and kinetics is non-linear. At 5 mg/kg body weight the majority of admin istered 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 expl ains 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 benzoy l ring was mostly excreted in th e urine. Approximately 50% of the aniline-ring metabolites were excr eted in the urine or feces.

In the two generation rat reproduction study, hexa flumuron 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 termit es containing hexaflumuron.

EFED Response:

Because mammalian species consume termites, e xposures and subsequent risks to mammals, cannot be precluded. However, after the cite d 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 term ites locate the untreated wood monitoring devices, and it is subsequently replaced with Shatter ® termite bait containing hexaflumuron, the “dosed” termites take the hexa flumuron back to the colony. The hexaflumuron is efficiently passed through trophall axis from one termite to another in the co lony. As with other insect growth regulator insecticides, time to term ite mortality is not dose dependent, i.e. termites that consume more hexaflumuron do not die fast er than those who consum e less. The termites that have received a dose of hexaflumuron are prevented from molti ng. In any one treated colony, enough of the worker caste dies such that the colony can no long er 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 ca nnot 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 mo lting (ecdysis) to th e next developmental

stage.22 of 23 EFED Response:

EFED appreciates the detailed explanation of he xaflumuron’s mode of action and its intended effect on the termite colony as a whole. As noted above, it is possible th at 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 w ould not contain hexaflumuron. Similarly, amphibians and reptiles will not seek the hexaflumuron-containing cellulose bait as a food source, yet may opportunistically find hab itat protection within a termite station and perhaps consume a termite.

Secondly, the data previously presented demonstr ates 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 repr oduction are unaffected by hexaflumuron.

Due to the use pattern, hexaflumuron will not pos e 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. Furthermor e, animals which prey on shrews and other animals that may consume hexa flumuron-treated termites would likewise be exposed to a very low concentration of h exaflumuron that would pose minimal risk.

Therefore, there would be minimal risk to mammals, amphibians, and reptiles which may directly or indirectly cons ume hexaflumuron via termites.

EFED Response:

As indicated above, EFED has identified repres entative 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 wo rker termites while they are above ground ( e.g ., in plants) as well. Therefore, because there is po tential for exposures of mammals, birds, reptiles and terrestrial-phase amphibians to hexaflum uron (through consumption of contaminated termites) toxicity data are neces sary to quantify the acute and ch ronic effects of hexaflumuron to these taxa. DAS has not provided sufficient eviden ce to preclude exposure and subsequent risks of non-target insects to hexaflumuron. Therefore, EFED is re questing data to determine relevant

effect levels for these taxa.23 of 23 Because of the potential exposur es of these taxa to hexaflum uron, EFED does not agree with DAS’s proposed revisions to the conceptual mode l. Based on available information, EFED will conduct ecological and endangered species assessments of hexafl umuron 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 (beg inning on Page 12 of 34) of the Problem Formulation, a risk hypothesi s described the predicted re lationship among the stressor, exposure, and assessment endpoint response, al ong with the rationale for their selection.

For hexaflumuron, DAS proposes the followi ng 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 in cluding birds, mammals, amphibians, reptiles, and terrestrial insects when used in accordance with the product labeling. Likewise, federally-listed thre atened and endangered species as well as non-listed species would be unaffected.

EFED Response:

As indicated above, EFED has identified repres entative 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 ther e is potential for exposures of mammals, birds, reptiles and amphibians to hexaflumuron (through consumption of contaminated termites) toxicity data are necessary to quantify th e acute and chronic effects of hexa flumuron 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 exposur es of these taxa to hexaflum uron, EFED does not agree with DAS’s proposed risk hypothesis. Based on avai lable information, EFED will conduct ecological and endangered species assessments of hexaflumuron using the risk hypothesis that is stated in the problem formulation.