Hexaflumuron Case 7413 

www.regulations.gov 

Docket Number EPA-HQ-OPP-2009-0568 

Pesticide Re-evaluation Division 

Hexaflumuron 

Interim Registration Review Decision 

Interim Registration Review Decision 

Case Number 7413 

Approved by: 

Date: 

March 2015 

~~ ,,'), 

Richard P. Keigwin, Jr. 

Director 

Pesticide Re-evaluation Division 

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Docket Number EPA-HQ-OPP-2009-0568 

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I. INTRODUCTION 

Interim Registration Review Decision 

This document is the Environmental Protection Agency's (EPA or the agency) Interim 

Registration Review Decision for Hexaflumuron (PC code 118202) and is being issued pursuant 

to 40 CFR sections 155.56 and 155.58. A registration review decision is the agency's 

determination whether a pesticide meets, or does not meet, the standard for registration in the 

Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). For further information on 

hexaflumuron, additional documents can be found in EPA's public docket (EPA-HQ-OPP-2009-

0568) at www.regulations.gov. 

FIFRA, as amended by the Food Quality Protection Act (FQPA) of 1996, mandated the 

continuous review of existing pesticides. All pesticides distributed or sold in the United States 

generally must be registered by the EPA based on scientific data showing that they will not cause 

unreasonable risks to human health or to the environment when used as directed on product 

labeling. The registration review program is intended to make sure that, as the ability to assess 

and reduce risk evolves and as policies and practices change, aII registered pesticides continue to 

meet the statutory standard of no unreasonable adverse effects. Changes in science, public 

policy, and pesticide use practices will occur over time. Through the registration review 

program, the agency periodically re-evaluates pesticides to make sure that as these changes 

occur, products in the marketplace can continue to be used safely. Information on this program 

is provided as www.epa.gov/oppsrrdl/registration review/. 

In 2006, the agency implemented the registration review program pursuant to FIFRA section 

3(g) and will review each registered pesticide every 15 years to determine whether it continues to 

meet the FIFRA standard for registration. 

The first product containing hexaflwnuron was registered in 1994. It was not subject to 

reregistration because it was registered after November 1984. Pursuant to 40 CFR § 155.50, the 

agency formally initiated registration review for hexaflumuron (case 7413), in September 2009. 

The following list highlights significant events that have occurred during the registration review 

of hexaflumuron and the documents that can be found in public docket (EPA-HQ-OPP-2009-

0568, accessible at www.regulations.gov). 

• September 23, 2009 - Issuance of the Hexaflumuron Summary Document and 

Preliminary Workplan (PWP)for Registration Review for a 60-day public comment 

period, along with the Scoping Document and Problem Formulation for hexaflumuron. 

• March 17, 2010 - Final Work Plan (FWP) for hexaflumuron was issued. Two comments 

were received during the comment period for 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 - Generic Data Call-In (GDCI) for hexaflumuron was issued. Data 

required under the GDCI included: Honey Bee Acute Oral Toxicity Test; UV N isible 

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Light Absorption; Avian Reproduction Test; Field Test for Pollinators; and Terrestrial 

Plant Toxicity Tests. 

• May 28, 2014 - The agency issued the Preliminary Ecological Risk Assessment and 

Endangered Species Effects Determination for Hexaflumuron and the Hexaflumuron. 

Human-Health Risk Assessment in Support of Registration Review for a 60-day public 

comment period. 

• September 2014 - The agency issued the Hexaflumuron Proposed Interim Registration 

Review Decision, for a 60-day public comment period. One comment was received. 

• March 2015 - The agency is now publishing the Interim Decision for Hexaflumuron in 

docket number EPA-HQ-OPP-2009-0568, which can be accessed at 

www.regulations.gov 

Public Comments to the Proposed Interim Decision for Registration Review 

During the 60-day public comment period following the publication of the Proposed Interim 

Registration Review Decision for Hexaflumuron, one comment was received from the Center for 

Biological Diversity. The comment addressed the agency's responsibilities under the Endangered 

Species Act (ESA). The comment is summarized herein along with the agency's response. The 

comment in its entirety is located in the hexaflumuron registration review docket (EPA-HQOPP-2009-0568). 

Comment Submitted by the Center for Biological Diversity in EP A-HQ-OPP-2009-0568-

0024 

Comments: The Center for Biological Diversity (CBD) comments focus 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. Specifically, CBD opposes the proposed decision for hexaflumuron prior to 

completion of consultation with the Services. CBD notes that the agency stated in the Ecological 

Risk Assessment that use of hexaflumuron "May Affect" listed birds, reptiles, terrestrial-phase 

amphibians and mammals. 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 address many of the concerns raised by CBD as part of 

the implementation plan for assessing the risks to listed species based on the recommendations of 

the April 2013 National Academy of Sciences (N AS) report. The agency is currently working 

with its federal counterparts and other stakeholders to implement an interim approach for 

assessing potential risk to listed species and their designated critical habitats. At this time the 

agency's decision is only an interim one. Once the scientific methods necessary to complete risk 

assessments for listed species and their designated critical habitats are finalized, the agency will 

complete its endangered species assessment for hexaflumuron and issue a final decision for 

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registration review. See Section IV. (C.) for a description of the agency's plan to address risks to 

endangered species and critical habitat. 

II. USE AND USAGE 

The agency has collected information showing that the amount of usage of hexaflumuron in 

recent years has been negligible. Data submitted by Dow Agrosciences showed usage in 2003 -

1,455 lbs.; 2004- no information is available; 2005 - less than 5 lbs.; 2006- less than 5 lbs.; 

2007 - less than 10 lbs.; 2008 - less than 5 lbs.; and 2009 - less than 5 lbs. A search of the 

California Department of Pesticide Regulation's Pesticide Use Reporting Database 

(bttp://www.cdpr.ca.gov/docs/pur/purmain.htm) showed usage of products containing 

hexaflumuron in California is similarly low through 2012, with 0.02 lbs applied in 2009; 0.09 

lbs. applied in 2010; and 5.6 lbs. applied in 2012. Ifhistoric;al trends in usage continue, the 

likelihood of risk is expected to remain at very low levels. 

III. SCIENTIFIC ASSESSMENTS 

A. Human Health 

A summary of the agency's human health risk assessment is presented below. For detailed 

discussions of all aspects of the human health risk 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) which can be accessed at http://www.regulations.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 toxicity profile for hexaflumuron is low, no human health toxicity endpoints were 

identified in the database. In addition, residential exposure to hexaflumuron is expected to be 

negligible because of the enclosed delivery system (enclosed in a bait station and impregnated in 

a cellulose 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 also not required. · 

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Occupational Assessment 

Interim Registration Review Decision 

Hexaflumuron is registered for products with both residential and commercial use and is used 

by professional applicators (not a restricted use pesticide). However, based upon its delivery 

system, 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 Updated Review of Hexaflumuron 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 chemical, therefore there are no U.S. tolerances 

established for hexaflumuron. 

B. Ecological 

A summary of the agency's ecological risk assessment is presented below. The agency 

used the most updated agency science policies and risk assessment methodologies to prepare a 

risk assessment in support of the registration review of hexaflumuron. For a detailed discussion 

see Registration review: Preliminary Ecological Risk Assessment and Endangered Species 

Effects Determination/or Hexaflumuron, dated March 18, 2014, in the public docket (EPA-HQOPP-2009-00568) which can be accessed at http://www.regulations.gov/. 

1. Environmental Exposure 

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

predicted slight mobility in soil indicate that hexaflumuron is not likely to dissolve in moisture 

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

from bait stations is expected to be low. As a precaution, labels prohibit the use of bait stations 

in depressions, low areas, or near water sources at or 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 ground-dwelling bees and other terrestrial 

invertebrates. Additionally, due to the placement of active ingredient within a cellulose matrix 

(few species have the ability to digest), and the placement locations of the bait station (i.e., 

residential and urbanized areas) reduces the likelihood of exposure to non-target organisms by 

hexaflumuron. 

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2. Risk Conclusions 

Mammals 

Docket Number EPA-HQ-OPP-2009-0568 

Pesticide Re-evaluation Division 

Interim Registration Review Decision 

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 adjusted to account for the dietary profile and size of the target 

species). 

Acute RQs were estimated 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 into 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. 

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Aquatic Organisms 

Docket Number EPA-HQ-OPP-2009-0568 

Pesticide Re-evaluation Division 

Interim Registration Review Decision 

Given the method of application and its chemical properties, hexaflumuron has a low 

likelihood of runoff jnto aquatic ecosystems and contributing to risk to aquatic organisms. Any 

hexaflumuron that does leach from bait stations is likely to bind to soils. In addition, to further 

avoid any leaching or movement of hexaflumuron into an aquatic environment, current 

hexaflumuron labels prohibit the use of bait stations " in depressions, low areas, near ponds, 

streams, springs, other water sources, or near downspout openings when 1he bait or its 

hexajlumuron contents could be washed out of the bait station into water at or near the surface 

of the ground." Due to the low potential for exposure, the agency did not estimate RQs for 

aquatic organisms, including aquatic invertebrates, fish, and aquatic plants. 

3. Ecological Incidents 

In November, 20 l 3, a review of both the Ecological Incident Information System (EIIS) 

database and the Avian Incident Monitoring System (AIMS; 

http://www.abcbirds.org/abcprograms/policy/toxins/aims/aims/index.cfm) was conducted for 

incidents involving hexaflumuron (AIMS is a database administered by the American Bird 

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 National Pesticide Information Centers 

(NPIC), which included the years from 1995 through 2013. Ten incidents were identified in 

NPIC where hexaflumuron was mentioned, however none of the incidents _involved wildlife, and 

none were definitively linked to hexaflumuron. 

IV. Risk Characterization 

A. Human Health Risk 

Based on its low toxicity profile and negligible potential for exposure, 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-based 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 contaminated food 

item (in this case hexaflumuron-contarninated termites). The conservative assumption of 100% 

of the diet, inherently reflects other presumptions such as full availability of the contaminated 

food source, and a lack of natural pressures (i.e., predation) that would otherwise limit an 

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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 of hexaflumuron 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 populations of wildlife. In addition, the vast 

majority of types of species that largely rely on termites for a source of food are 

found outside of the U.S. One key exception is the nine-banded armadillo, which is 

not a federally listed or endangered species. 

• Use of hexaflumuron is very low, and such low use naturally reduces potential 

exposure and therefore risk. 

While certain RQs for birds and mammals exceed the LOC, considerations 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 estimated RQs 

and the additional considerations together, it believes that the actual exposure and risk from 

hexaflumuron is low. 

C. Endangered Species Assessment 

As part of the Preliminary Ecological Risk Assessment for Registration Review for 

hexaflumuron, EPA also completed a.risk assessment of risk for endangered and threatened 

(listed) species and critical habitat. Based upon the risk analysis for hexaflumuron, RQ estimates 

were below the Listed species LOC for certain taxa (i.e., aquatic organisms and plants). 

Therefore, a "No Effect" determination was concluded for aquatic organisms and plants. In 

addition, EPA is making a "Not Likely to Adversely Affect" (NLAA) determination for listed 

birds, mammals, and terrestrial invertebrates based on conservative assumptions 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 designated critical habitats based on the 

· currently registered uses ofhexaflwnuron. EPA will initiate consultation with the U.S. Fish and 

Wildlife Service to obtain concurrence on the NLAA detem1ination for listed birds, mammals, 

and terrestrial invertebrates. 

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D. Endocrine Disruptor Screening Program 

Interim Registration Review Decision 

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential 

adverse outcomes from exposure to chemicals. Collectively, these studies include acute, 

subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, 

developmental, reproductive, and general or systemic toxicity. These studies include endpoints 

which may be susceptible to endocrine influence, including effects on endocrine target organ 

histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, 

reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates 

acute tests and chronic studies that assess growth, developmental and reproductive effects in 

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

EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment 

scenarios from the existing hazard database. However, as required by FFDCA section 408(p), 

hexaflumuron is subject to the endocrine screening part of the Endocrine Disruptor Screening 

Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a "naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate." The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or 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 of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

Under FFDCA section 408(p), the agency must screen all pesticide chemicals. Between 

October 2009 and February 20 l 0, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of 

chemicals identified for EDSP screening was published on June 14, 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

2

1 

In the interim, EPA is making no human health or environmental safety findings associated 

with the EDSP screening of hexaflumuron. Before completing this Registration Review, the 

agency will make an EDSP FFDCA section 408(p) determination. 

11 1 See h t tp: //www.regu l a t i ons.gov/ #!do cumentDetail;D=EPA-HQ-OPPT-2009-0477-

0074 for the fina l s econd list of chemical s . 

12l'ht tp : //www .ep a.gov/ endo/ 

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Interim Registration 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 low. The agency has estimated RQs for birds and mammals 

that exceed the agency's acute and chronic LOCs, but when viewed in the context ofrisk 

characterizations, these are likely limited in scale (i.e., degree of potential risk) and in scope (i.e., 

extent of the potential risk) and any risks do not exceed benefits. The limited use of 

hexaflumuron further indicates limited exposure and therefore limited potential risk. When the 

risk estimates, risk characterizations, and use and usage of hexaflumuron are considered 

together, the agency does not believe that any additional risk mitigation for hexaflumuron is 

necessary at this time. Therefore, at this time, the agency is requiring neither additional risk 

mitigation nor additional data for the registration review of hexaflumuron. 

B. Interim Registration Review Decision 

In accordance with 40 CFR Sections 155.56 and 155.58, the agency is 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 labeling are needed at this time. 

In this Interim Registration Review Decision, EPA is making no human health or 

environmental safety findings associated with the EDSP screening of hexaflumuron, nor is it 

making a complete endangered species finding. The agency's final registration review decision 

for hexaflumuron will occur after an ESA 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 with the Services and an EDSP FFDCA Section 408 (p) determination has been 

made. 

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