Hexaflumuro n Case 74 13 www. regulations.gov Doc ket Number EPA

- HQ

-OPP

-2009-0568 Pesticide Re

-evaluation Divi sion



# Hexaflumuron I nterim Registration R ev iew Decision



# Interim Registration Review Decision Case Number 7413

Approved by:



### Date: 

# March 2015**~~ ,,'),**  Ri chard P. Keigwin, Jr
. Director Pesticide Re

- evaluation Division
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- /0-.QOIS

1Hexatlumuron Case 7413 w11 w.rcgu l at

ions
. 1?.o v Docket Number EPA-HQ-OPP

-2009-0568 Pesticide Re-evaluation Divi sion 

### I. 

### INTRODUCTION Interim Registration Review Decision

This document is the Environme ntal Prot ection Agency's (EPA or the agency) 

### Interim Registration Review Decision for He xaflumuron (PC code 118202) and is being issued pursuant to 40 CFR sections 1 55.56 and 1 55.58
. A registration review d ecision i s the agency 's determ ination whether a pesticide meets , or does not meet , the standard for registration in the Federal Insecticide , Fungicide , and Ro denticide Act (FIFRA). For further information on hexaflumuron, add itional documents can be found in EPA ' s public docket (EPA -HQ-OPP -2009

- 0568) at www. reg ul a ti o n s .gov . FIFRA, as amended by the Food Qualit y Protecti on Act (FQPA) of 1 996, mandated the co ntinu ou s review of ex isting pesticide s . All pesticides distributed o r sold in the United States gen e rally mu s t be registered by the EPA based on scient ifi c data show in g th at they will not cause unreasonab le risks to human health or to the environment when used as directed on product lab el in g. The registration review program is intended to make sure that , as the ability to assess and reduce risk evo lves and as policies and prac ti ces change , aII registered pesticides cont inue to meet the statutory standard of no unre aso nab le adverse effects. Changes in science, public po licy , and pesticide use practices will occur over time. Through the registration review program, the agency periodically re-evaluates pesticide s to make sure that as these changes occur , products in the marketplace can continue to be used safely. Information on this program i s pro v ided a s www . e pa. gov / o ppsrrd l/re gi strati on rev iew/
. In 2006, the agen cy implemented the registration review program pursuant to FIFRA section 3(g) and will review each registered pest i cide every 15 years to determine whether it continues to meet the F IFRA standard fo r registration. T he first product containing hexaflwnuron was regi stered in 1994. It was no t subject to reregi s tration because it was regi stered after November 1 984. Purs uant to 40 CFR § 155.50, the agency forma ll y initia ted registration re v iew for h exafl umuron (case 7413), in September 2009. The fo llo w in g lis t hi ghli ghts significant e v ents that hav e occurred during the registration revie w of he xafl umuro n and th e documents that can be found in pu blic docket (EPA-HQ-OPP-2009- 0568 , access ibl e at www.regulations.gov).

• September 23, 2009

- Is suance of the 

### Hexaflumuron Summary Document and Preliminary Workplan (PWP )for R egistration Review for a 60-day public comment period , a long with the Scoping Document and Problem Formulation for hexaflumuron
.
• March 17 , 2010

- 

### Final Work Plan (FWP ) for hexaflumuro n was i ss u ed. Two comments we re received during the comment period fo r the PWP following the opening of the public docket. Comments submitted by the registrant indicated that certain data on environmental fate were unnecessary , and supplemental ecotoxicity data were provided. Neither comment resulted in modification to the work plan for hexaflumuron.

• September 15 , 2010

- G eneric Data Call -In (GDC I) for hexaflumuron was issued. Data required under the G DCI included: Honey Bee Acute Oral Toxicity Test; UV N i sible

2Hexanumuron Case 7413 WW\\ .re gulations .gov Docket Number EPA-HQ-OPP-2009-0568 Pesticide Re- evaluation Divi sio n Interim Regis tration Review Decision Light Absorption ; Avian Reproducti on Test; Field Test for Po lli nators ; and Terrestrial Plant Toxicity Tests.

• May 28 , 2014

- The agency issued the Preliminary Ecological Risk Assessment and Endangered Sp ec ies Effects Determinationfor Hexaflumuron and the Hexaflumuron. Human-H ealth Ri s k A ssessment in Support of Registration Review for a 60 -day public comment peri od.

• September 2014

- The agency issued the Hexaflumuron Proposed Interim Registration Review Dec ision, for a 60

- day public comment period. One comment was received.

• March 20 1 5

- The agency is now publi shi ng the Interim Decision for Hexaflumuron in docket number EPA- H Q -OPP -2009-0568, which can be accessed at www.regulation s .gov Public Co mm ents to the Proposed Interim Decision for Regi stration Review During the 60-day public commen t period foll o wing the publi cation of the Proposed Interim Registration Review Deci s ion for Hexaflumuron , one comment was received from the Center for Biological Diversity. The comment addressed the agency's r espon sibilit ies under the Endangered Species Act (ESA). The comment is summarized herein alon g with the agency's response. The commen t in its entirety i s located in the hexaflumuron registrati on review docket (EPA-HQOPP-2009

- 0568). Comment Submitted by the Center for Biological Diversity in EPA - HQ -OPP- 2 009-0568- 0024 Comments: The Center for Biological Diversity (CB D) comments focu s on EPA 's independent duty under the Endangered Species Act (ESA) to consult with the U.S. Fish and Wildlife Service and the National Marine and Fisheries Service (Services) on the registration review of hexaflumuron. Specifica ll y, CBD opposes the propo se d dec i sion for hexaflumuron prior to completion of consultation with the Services. CB D note s that the agency state d in the Ecological Ri sk Assessment that use of hexaflumuron " May Affect" lis ted birds, reptiles , terrestrial

-phase amphibians and mammal s. In addition , CBD recommends adding specific precautionary label language to protect l:isted species and critical habitat. Agency Response: The agency has reviewed the comments from CBD on the hexaflumuron Proposed Interim Decision and plans to addres s many of the concerns raised by CB D as part of the implementation plan for assessing the risks to li sted species based on the recommendations of the April 2013 National Academy of Sciences 

### (N AS) report. The agency is currentl y workin g with its federal counterparts and other stakeho lders to implement an interim approach for ass essing potential ri s k to li sted species and their de s ignated critical habitats. At this time the agency 's decision is o nl y an interim one. Once the scientific methods nece ssa ry to complete risk ass e ss ments for li ste d species and their design ated cri tical habitats are fin a lized , the agency will complete its endangered specie s assessment fo r hexaflumuron and issue a final decision for

3Hexaflumuron Case 7413**www .r** **~g ul** **ti s.go** **v** Docket Numbe r EPA

- HQ-OPP-2009-0568 Pesticide Re -e valuation Division Interim Registration Rev i ew Decision
reg i strat ion review. See Section IV. (C.) for a description of the agency's plan to address ri sks to 

### endangered species and critical habitat
. II. USE AND USAGE The agency has collected information showing that the amount of usage of hexaflumuron in rece nt years has been negligible. Data submi tted by Dow Agrosciences showe d usage in 2003

- 1,455 lbs.; 2004- no information is availab le; 2005

- less than 5 lbs .; 2006- less than 5 lbs.; 2007

- le ss than 10 lbs.; 2008

- less than 5 lbs.; and 2009

- le ss than 5 lbs. A search of th e Ca lifornia Department of Pesticide Regulation's Pesticide Use Reporting Da tabase (bttp: //www
.cd pr.ca . gov/do cs /pur /purm a in.htm) showed usage of products containing h exaflumuron in California is similarly lo w through 2012, with 0.02 lbs applied in 2009; 0.09 lbs. appl ied in 2010; and 5.6 lbs
. applied in 2012. Ifhistoric;al trends in usage continue, the likelihood ofrisk i s expected to remain at very low le vels
. III . SCIENTIFIC ASSESSMENTS A. Human Health A summary of the agency's human health risk assessment i s presented below. For detailed discussions of all aspects of the human health ri sk assessment, see Hexaflumuron. Human

- Health Risk Assessment in Support of Registration Review, dated March 5, 2014, in the public docket (EPA-HQ-OPP-2009-00568) whi ch can be accessed at http: //www .r e gulati on s .gov/
. 1. Human Health Risk Summary Dietary Assessment No dietary assessment was conducted because there are no food uses for hexaflumuron, and therefore no dietary exposure is expected. Residential Assessment The tox icity profi le for hexaflumuron is low, no human health toxicity endpoints were identified in the database. In additi on, res idential exposure to hexaflumuron is expected to be negligible because of the enc losed delivery system (enclosed in a bait station and impregnated in a cell ulose matrix). Therefore, residential exposure was not assessed. Aggregate Assessment Due to the lack of a need of a dietary or residential exposure assessment, an aggregate assessment is a lso not required. ·

4Hexaflumuron Case 7413 www.regulations.gov Docket Number EPA-HQ-OPP-2009-0568 Pesticide Re

- evaluation D i vision 

### Occupational Assessment Interim Regis tration Review Decision

Hexaflumuron i s registered for products with both residential and commercial use and is used by professional applicators (not a restricted use pe s ticide). However, ba sed upon its delivery syste m, occupational handler and post application exposures to hexaflumuron are not expected , and therefore an occupational assessment was not conducted. 2. Human Health Incidents As indicated in the 

### U pdated Re view of Hex aflumuron Incident Reports document, at the time of the initial docket opening in 2009, the agency reviewed the existing poisoning incident data on hexaflumuron. The report queried the OPP Incident Data System (IDS) and represents incidents occurring in the U.S. from 2002 to 2009. During that time period , there was only one incident report, which appeared to be general and not clearly related to exposure to hexaflumuron. Based upon the lack ofincidents found during its initial review, the agency has not updated its human incidents review for hexaflumuron. 3. Food Tolerances Hexaflumuron is not a food-use chemi cal, therefore there are no U.S. tolerances estab li s hed for hexaflumuron. B. Ecological A summary of the agency's ecological ri s k assessment is presented below. The agency use d the most up dated age ncy science policies a nd risk assessment methodologies to prepare a risk assessment in s upport of the registration review o f hexaflumuron
. For a detailed discussion see R egistration review: 

### Preliminary Ecological Risk Assessment and Endangered Species Effects Determination/ o r H exaflumuron , dated March 18, 2014 , in the public docket (EPA-HQOPP-2009-00568) which can be accessed at http: //www.regulation s .gov /
. 1. Environmental Exposure Hexaflumuron' s low so lub ility in water , high octanol-water partition coefficient, and predicted s light mobility in soi l indicate that hexaflumuron is not likely to dissolve in moi sture that may enter the bait s tations , so the likelih ood of exposure from runoff of chemical leached from bait stations is expected to be low. As a prec a ution , labels prohibit the use ofbait stations in depressions, low areas, or near water source s at o r near the surface of the ground. The plastic bait station limit the availability of hexaflumuron to non-target organisms. The entrances to the bait stations have been configured to be large enough (2.5 mm) to allow termites to enter while being small enough**~o** prevent entry by most native groun d-dwelling bees and other terrestrial invertebrates. Additionally , due to the placement of active ingredient within a cellulose matrix (fe w species have the abil ity to digest), and the placement locations of the bait station (i.e
. , residential and urbani zed areas) reduces the likelihood of exposure to non-target organisms by hexaflumuron.



### 5Hexaflumuron Cas e 7413 ww w. r eg ul at io ns . go v 

### 2. Risk Conclusions Mammals Docke t Number EPA-HQ-OPP-2009-0568 Pesticide Re-evaluation Division Interim Registration Review Deci s ion

The agency estimated potential exposure and risk to terrestrial organisms based on potential consumption of termites contaminated with hexaflumuron. This was done by estimating the quantity (mass) ofhexaflumuron per termite, and deriving both dietary-based risk estimates (i.e ., where the dose level is taken directly from the application value and is not adjusted to account for the dietary profile of the target species) and dose-based risk estimates
. (where the dose level and toxicity endpoint are adjus t ed to account for the dietary profile and size of the target species). Acute RQs were est imated for mammals using non-definitive endpoints (i.e., where the highest tested dose in the eco-toxicity study did not elicit a significant toxic effect). Using the non-definitive endpoints, risk quotient (RQ) values did not exceed the agency's acute Level of Concern (LOC) where the acute LOC is 0.5. Chronic dose-based RQ estimates for mammals range from below the chroriic LOC to above the chronic LOC (where the chronic LOC 

## = 1.0). RQ estimates were 1.58 for medium-sized mammals and 1.85 for small-sized mammals. Birds Similar to the assessment for mammals, ecological risk to birds (also acting as a surrogate for reptiles and terrestrial-phase amphibians) was assessed based on consumption of termites contaminated with hexaflumuron. The estimated acute avian dose-based RQ value is 0.12 which exceeds the acute LOC for listed small birds (where the acute LOC 

## = 0.1 ). However, this estimate assumes birds consume eight times the amount they are expected to consume in a day. The acute avian dietary-based RQ value is below the acute LOC. The chronic dietary

- based RQ is estimated to be 3.6, exceeding the chronic LOC. Terrestrial Invertebrates The bait cartridges for hexaflumuron are designed so that invertebrates, other than termites, cannot gain access to the active ingredient. While there are some terrestrial invertebrate species that may be small enough to access the bait, the active ingredient is impregnated int o a cellulose matrix which most terrestrial invertebrates are unable to consume. As a result, exposure -to nontarget terrestrial invertebrates is expected to be low, and therefore RQs were not estimated. Terrestrial Plants Given the mode of action as well as the application method of hexaflumuron (contained in a bait station) and its chemical properties, the agency does not believe that exposure to, or effects from hexaflumuron to non-target terrestrial plants, is likely. Therefore, RQs for non-target terrestrial plants were not estimated.



### 6Hexaflumuron Case 7413 www.regulat io ns . go v Aquatic Organisms Docket Number EPA-HQ-OPP-2009-0568 Pesticide Re-evaluation Division Interim Registration Review Decision

Given the method of application and its chemica l properties, hexaflumu ron has a low like lihood of runoff jnto aquatic ecosystems and contributing to risk to aquatic o rgani sms. Any hexaflumuron that does leach from bait stations i s likely to bind to so il s. In additio n , to further avoid any leaching or movement of hexaflumuron into an aquatic environme nt , current hexaflumuron labels prohibit the use of bait stations " in depressions, low areas, nearponds, s treams , springs , othe r water sou rces, or near down s pout openings when 1he bait or its hexajlumuron contents co uld be washed out of the bait s tation into water at or near the surface of the ground." Due to the low potential for exposure , the agency did not estima te RQs for aquatic organisms, including aquatic invertebrates, fish, and aquatic plants. 3. Ecological Incidents In November, 20 l 3, a review of both th e Eco logical Incident Information System (EIIS) database and the Av i an Incident Monitoring System (AIMS; http : //www .abcbird s .org/abcprograms/policy/ toxin s/aims/ aims /i ndex.cfm) was conducted for incidents involving hexaflumuron (AI MS is a database administered by the American B ird Conservancy that contains publicly available data on reported avian incidents involving pesticides). No ecol-0gica1 incidents involving hexaflumuron were reported in either database. The agency also reviewed reports from the Nati onal Pe stic ide Information Centers (NPIC), which included the years from 1995 through 2013. Ten incidents w ere identified in NPIC where hexaflumuron was mentioned , however none of the incidents _invo lved wildlife , and none were definitively linked to hexaflumuron. IV. Risk Characterization A. Human Health Risk Based on its low tox icity profile and negligible potential for expos ure, the agency believes that the potential for human health risk from hexaflumuron is low. Therefore, no characterization of human health risks is necessary . B. Ecological Risk Although LOCs were exceeded for birds and mammals that may feed on contaminated termites, consideration of several inputs to the risk estimate has led EPA to determine that there

. is low potential for exposure, and therefore low risk from hexaflumuron. While dietary-ba se d risk estimates and dose-based risk estimates offer different characterizations of potential risk, both approaches are based on conservative assumptions regarding the percent ( i. e., 100 %) of an animal 's daily diet comprised of the contam inated food item (in this case hexaflumuron-contarninated te r mites). The conservative assumption of 100% of the diet, inherently refl ect s other presumptions such as full availability of the contaminated foo d source, and a lack of natural pressures (i.e., predation) that would otherwise limit an

7Hexaflumuron Case 7413 ww w .regulat i ons.go v Docket Number EPA-HQ-OPP-2009-0568 Pesticide Re-evaluation Division Interim Registration Review Decision organism's ability to feed solely on one food source. The possibility of continuous availability 

### of contaminated termites is further characterized by other considerations noted by the agency in the Preliminary Ecological Risk Assessment and Endangered Species Effects Determination for Hexajlumuron including:

• The amount ofhexaflumuron circulating within the colony at any single time is only a fraction of what is consumed over the entire baiting period (estimated to be approximately 6 months to a year). • The non- target organism (i.e., the mammal or bird) will likely consume both tainted and untainted termites. • The window of time between when termites are exposed and are available for consumption is small, since hexaflumuron is designed to kill the termite. • Accessibility to contaminated termites may also be considered low since termites are not considered an accessible prey item as most of their time is spent in underground tubes or in wood , and the caloric benefit of locating and consuming termites is low. • Hexaflumuron products are designed to protect manmade structures , and are not generally used in areas with large population s of wildlife. In addi t ion, the vast maj ority of types of species that largely rely on termites for a source of food are found outside of the U.S. One key exception i s the nine-banded armadillo , which is not a federally listed or endangered species. • Use ofhexaflumuron is very low, and such low use n aturally reduce s potential exposure and therefore risk. While certain RQs for birds and mammals exceed the LOC, cons iderations involving exposure help infonn the potential risk. These considerations inform the potential frequency or magnitude of risk and provide a more realistic picture. When the agency views es timated RQs and the additional considerations together, it believes that the actual exposure and risk from hexaflumur on is low. 

### C. Endangered Species Assessment As part of the Preliminary Eco logical Risk Asses s ment for Registration Review for hexaflumuron , EPA also completed a .risk assessment of risk for endangere d and threatened (listed) species and critical habitat. Based upon the risk a n a lysis for hexaflumuron, RQ estimates were below the Listed spec ies LOC for certai n taxa (i .e., aquatic organi s ms and plants). Therefore , a "No Effect" determination was concluded for aquatic organisms and plants. 

### In addition , EPA i s m a king a " Not Likely to Adversely Affect " (NLAA ) determin a tion for li sted bi rds , mamm als , and terrestrial in vertebrates based on conservative ass umption s used to derive the risk estimates , and limited exposure due to the use pattern of hexaflumuron. Also a "No Habitat Modification " determination was made for all desig nated critical habitats based on the

· currently registered uses ofhexaflwnuron. EPA wi ll init iate consultation with the U.S. Fi sh and Wildlife Service to obtain concurrence on the NLAA detem1ination for listed birds, mammals , and terrestrial invertebrates.



### 8Hexaflumuro n Case 74 13 www.re gulation s .go v Dock et N umber E PA-H Q-OPP-2009- 0 568 Pestici de Re-evaluati o n Divi s ion D. Endocrine Disruptor Scree ning Program Interim R e gi str a ti o n R ev iew Dec i s ion

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively , these studies include acute, subchronic and chronic toxicity , including assessments of carcinogenicity , neurotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocr in e influence, includ ing effects on endocrine targe t organ histopatho logy, o rgan weights , estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss , and sex ratios in offspring. For ecological hazard assessments , EPA evaluates acute tests and chronic studies that assess growth , developmental and reproductive effects in different taxonomic groups . As part ofits most recent registration decision for hexaflumuron, EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment sc enarios from the exi sting hazard database. However , as required by FFDCA secti on 4 0 8(p), hexaflumuron is subject to the endocrine screening part of t h e Endocri n e Disruptor Sc reening Program (EDSP). EPA has developed the EDSP to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wi ldlife similar to an effect produced by a "naturally occurring es trogen , or ot h er s u ch endoc rin e effects as the Admi nistrator may designate." The EDSP emp loys a two-tiered app roach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrogen, androgen , or thyroid (E , A , or 

## D hormonal systems . Chemicals that go through Tier 1 screening and are found to have the potential to interact with E , A, or T hormonal systems will proceed to the next stage ofthe EDSP where EPA will determine which, if any , of the T ier 2 tests are necessary based on the available data. T ier 2 testing is designed to identify any adverse endocr ine-related effects ca u sed by the substan ce , and establish a dose-response relationship between the dose and the E , A , or T effect. Under FFDCA section 408(p), the agency must screen all pesticide chemicals. Between October 2009 and February 20 l 0, EPA issued test orders/data cal l -ins for the first group of 67 chemicals , which co ntains 58 pestic i de active ingred ients and 9 inert in gred ients. A second list of chemicals identified for EDSP screening was pub lished on June 14, 2013r 1J and includes some pesticides scheduled for Registration Review and chemicals found in water. For further information on the status of the EDSP , the policies and procedures, the lists of chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website. 

### r 21 In the interim, E P A i s making no human healt h or en v ironmental safety findings assoc i ated w ith the EDSP screening of hexaflumuron. Before completing this Registration Review, the agency will make an EDSP FFDCA section 408(p) determinat ion.

1 1 1 See h t tp: // www.regu l a t i ons.gov/ #!do cu m entDeta il ;D = EPA-HQ-OP PT -2 009-047 7- 007 4 for the fina l s econd list of chemica l s . 12l'h t tp : // www .ep a.g ov / endo /


### 9Hexaflumuron Case 7413 ww w.regula t io n s .go v Docket Number EPA

- HQ-OPP-2009-0568 Pesticide Re-evaluation Division Interim Regi st ration Review Decision
V. INTERIM REGISTRATION REVIEW DECISION A. Risk Mitigation and Rationale As discussed in this document, there is very little usage of hexaflumuron in the U .S, and as a result benefits of hexaflumuron are l ow. The agency has estimated RQs for bi rds and mammals that exceed the agency's acute and chronic LOCs, but when viewed in the context ofrisk characterizat i ons, these are likely limited in scale 

### (i.e., degree of potential risk) and in scope 

### (i.e ., exten t of the potential ri sk) and any risks do not exceed benefits. The limited use of hexafl umuron further indicates limited exposure and therefore li mited potential ri sk. When the risk estimates, risk characteri zations, and use and usage of hexaflumuron are considered together, the agency does not believe that any additional risk mitigati on for hexaflumuron is necessary at this time. Therefore, at th i s ti me, the agency i s requiri n g neither additional risk mitigation nor additional data for the registration review of hexaflumuron. B. Interim Regis tration Review Decision In accordance with 40 CFR Sections 155
. 56 and 155.58, the agency i s issuing this Interim Registration Review Decision for hexaflumuron (case 7413). Except for the EDSP and ESA components of this case, the agency has made the following Interim Registration Review Decision: (1) no additional data are required at this time; and (2) no changes to the affected hexaflumuron registrations and their l abeling are needed at this time. In this Interim Registration Rev i ew Dec i sion, EPA is making no human health or environmenta l safety findings associated with the EDSP screening of hexaflumuron, nor is it making a complete endangered species finding. The agency's final registration review dec i sion for hexaflumu ron will occur after an E SA Section 7 consultation with the Services, and an EDSP FFDCA section 408(p) determination has been made
. VI. NEXT STEPS AND TIMELINE A . Implementation of Mitigation Measures As stated in Section V, no mitigation measures are required for hexaflumuron at this time. B . Final Registration Review Decision EPA will make a final registration review decision for hexaflumuron after ESA Section 7 consultation w ith the Servi ces and an EDSP FFDCA Section 408 (p) determinati on has been made.

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