1

OFFICE OF CHEMICAL SAFETY

AND POLLUTION PREVENTION

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

March 9, 2015

PC Code: 118205

MEMORANDUM DP Barcode: 423179

SUBJECT: Lufenuron Problem Formulation for Registration Review

FROM: Melanie Biscoe, MEM, Physical Scientist

Frank Farruggia, Ph.D., Biologist

Environmental Risk Branch 3

Environmental Fate and Effects Division (7507P)

REVIEWED

BY: Melissa Panger, Ph.D., Senior Biologist

Rosanna Louie-Juzwiak, RAPL

Environmental Risk Branch 3

Environmental Fate and Effects Division (7507P)

THROUGH: Dana Spatz, Chief

Environmental Risk Branch 3

Environmental Fate and Effects Division (7507P)

TO: Bonnie Adler, Chemical Review Manager

Jill Bloom, Team Leader

Linda Arrington, Chief

Risk Management and Implementation Branch 5

Pesticide Re-Evaluation Division (7508P)
2

Table of Contents

1. Executive summary................................................................................................................. 3

2. Introduction............................................................................................................................. 4

3. Use Characterization............................................................................................................... 4

4. Conclusions from Previous Risk Assessments....................................................................... 5

a. Ecological Risk Assessment ................................................................................................... 5

b. Drinking Water Exposure Assessments............................................................................... 6

c. Clean Water Act Programs .................................................................................................. 6

5. Environmental Fate and Transport.......................................................................................... 6

a. Transformation Products...................................................................................................... 7

6. Receptors................................................................................................................................. 7

a. Ecological Incidents............................................................................................................. 9

7. Exposure Pathways of Concern ............................................................................................ 10

8. Analysis Plan ........................................................................................................................ 10

a. Stressors of Concern .......................................................................................................... 10

b. Measures of Exposure........................................................................................................ 11

c. Measures of Effect ............................................................................................................. 12

9. Endangered Species Assessments...................................................................................... 12

10. Endocrine Disruptor Screening Program ....................................................................... 13

11. Preliminary Identification of Data Gaps ........................................................................ 13

a. Environmental Fate............................................................................................................ 13

b. Effects................................................................................................................................ 13

12. Bibliography ...................................................................................................................... 15
3

1. Executive summary

The Environmental Fate and Effects Division (EFED) has completed the preliminary problem 

formulation (attached) for the ecological risk and endangered species assessments to be conducted 

as part of the registration review of lufenuron. The problem formulation provides an overview of 

the risk assessment approach, the environmental fate, ecological effects, and potential risks

associated with the use of lufenuron, as well as uncertainties unique to risk assessment of 

lufenuron. This document also identifies additional studies that would be beneficial to the 

conduct of an ecological risk assessment. 

In this problem formulation, it is assumed that the plastic bait station limits the availability of 

direct contact with lufenuron to non-target organisms. There have been no new uses assessed 

since the new chemical risk assessment (USEPA 2004); therefore, with the exception for 

evaluating potential exposure to terrestrial vertebrates, this assessment continues to represent the 

risks to non-target organisms. Additionally, use of cellulose materials as the food-based delivery 

system and the placement within bait stations around residential and urbanized areas reduce the 

likelihood that native ground-dwelling bees and other non- target terrestrial invertebrates would 

come into contact with lufenuron, so these risks are considered of minimal concern. Therefore 

this problem formulation describes the analysis of potential terrestrial vertebrate dietary exposure, 

through the consumption of termites that have fed on bait, and is considered the only major route 

of exposure in this assessment. Thus, this document provides a brief overview of the chemical, 

and summarizes risk concerns previously identified in the assessment done for the initial new 

chemical registration. 

This problem formulation has established that termites contaminated with lufenuron constitute a 

complete exposure pathway to ground-feeding insectivorous terrestrial vertebrates. This is likely 

to result in residues being incorporated into insect biomass (termites) over considerable periods of 

time. To estimate the risk to terrestrial vertebrates the following studies would be needed:

 Acute oral toxicity in a passerine bird: The exposure concept for this risk assessment 

places insectivorous birds as a non-target receptor via consumption of termites feeding on 

bait. The most likely insectivorous birds to be exposed would be passerines. 

 Avian reproduction studies for an upland game bird and a waterfowl species. These 

data are essential for evaluating the potential for lufenuron to affect the fitness of avian 

species through impacts to reproduction. The use of lufenuron in bait stations will likely 

involve long-term placement of treated baits. 

In addition, the following issues are uncertainties with the current labels concerning the 

application rate:

 Labels do not specify the amount of product present in each bait station.

 Labels do not specify the maximum number of bait stations that can be present on a 

designated area of land.
4

2. Introduction

Lufenuron is a benzoylphenylurea compound used to control termites. It is a chitin synthesis 

inhibitor that has relatively low solubility in water and low mobility in soils. The 

structure of lufenuron, as well as the chemical names and other identifiers can be found in Table 

1.

Table 1. Chemical Identification Information for Lufenuron

Chemical Names and 

Identifiers Chemical Structure

Common Name: Lufenuron

IUPAC Name: 3-[2,5-

dichloro-4-(1,1,2,3,3,3-

hexafluoropropoxy)phenyl]-

1-(2,6-difluorobenzoyl)urea

CAS No.: 103055-07-8

PC Code: 118205

Formula: C17H8Cl2F8N2O3

SMILES Code:

FC(C(F)(F)F)C(F)(F)OC1=C

C(Cl)=C(NC(=O)NC(=O)C2

=C(F)C=CC=C2F)C=C1Cl

Lufenuron is contained within plastic bait stations which are likely to protect the compound

from many routes of degradation as well as limit exposure to most non-target organisms.

Lufenuron is used exclusively in containerized bait stations, both above and below ground.

The environmental fate and ecological effects data associated with lufenuron, as well as its use, 

remain unchanged since its initial registration in 2004. EFED evaluated the ecological risk 

assessment and risk assessment addendum for lufenuron from 2004, considering the latest Agency 

science policies and risk assessment methodologies, to determine if sufficient data are available 

and if further updates are needed to support registration review (DP293833, DP295519). 

3. Use Characterization

Lufenuron was registered in 2004 as part of an Integrated Pest Management (IPM) program that 

includes lufenuron-impregnated baits together with termite monitoring/inspection. It was intended

to be used by state-certified, professional pest control operators in post-construction commercial, 

industrial, institutional, and residential areas. Although registered, it is EFED’s understanding that 

lufenuron products are not currently marketed or used in the United States.
5

Lufenuron products are ready-to-use, cellulose-based bait matrices containing lufenuron at 0.15% 

by weight, or 1500 mg a.i/kg bait, which are placed in either below-ground or secured aboveground hard plastic bait stations. Although the labels do not specify the exact weight of the bait 

material, the 2004 risk assessment estimated the bait weight to be 100 grams based on a sample 

bait station provided to EPA. Lufenuron labels also do not specify the maximum number of bait 

stations that can be present on a designated area of land, although the label states that 10 to 20 

stations per house should be sufficient for most situations. As labels are now, application rates of 

lufenuron applied to a unit area (i.e., lbs a.i./A) cannot be determined definitively.

4. Conclusions from Previous Risk Assessments

a. Ecological Risk Assessment 

The most recent, comprehensive assessment conducted for lufenuron is the new chemical risk 

assessment conducted in 2004. For this assessment, the end-use products, all of which were bait 

stations, were examined in conjunction with the physical and chemical properties, environmental 

fate and ecotoxicity of the active ingredient. The assessment was qualitative in nature. 

Table 2. Summary of Risk Concerns Identified for Lufenuron in Previous Assessments

Bird Mammal Terr.

Plant

Terr.

Invert Fish BCF Aquatic Inverts

Aquatic 

Plants Groundwater

Persist

-ence

Degradate 

of 

Concern

Noab NAac No?d NAa Noae No?a

d

Noae No?ad No Yes No

a Exposure considered unlikely.

b Assumes one full-day’s diet of a bobwhite quail is bait from bait stations; no chronic exposure expected. 

c No chronic data available.

d No data available.

e Complete dilution of 17 bait stations in the farm pond would approach saltwater invertebrate LC50 and exceed 

freshwater invertebrate LC50; in this scenario there is no concern for fish based on low toxicity.

“No” = LOCs have not been exceeded in previous assessments; NA = RQs have not been calculated previously.

Given that lufenuron was to be used in baits enclosed within rigid plastic bait stations, direct 

exposure potential to non-target plants and animals was expected to be minimal. Conclusions 

from the 2004 assessment include the following:

 The proposed use of lufenuron as a bait formulation contained in rigid plastic structural 

housings suggested a low risk to endangered and non-endangered aquatic and terrestrial 

organisms if and only if it is used as directed on the proposed label.

 Environmental exposures to lufenuron were expected to be low when used as directed on 

the label. Acute freshwater and saltwater invertebrate tests were invalid, but provided 

enough information to suggest lufenuron is very highly toxic to aquatic invertebrates. The 

potential for risks to aquatic invertebrates, especially benthic invertebrates, could be 

substantial if the bait housing is compromised, tampered with, or disposed in such a 

manner as to allow exposures in the aquatic environment.
6

 It was unclear how toxic lufenuron is on a chronic (reproductive) basis for birds. One 

study was invalid and the other, although supplemental, failed to establish a NOEC with 

effects observed at the lowest exposure level of 200 ppm. Nevertheless, it was considered 

to be virtually no likelihood that birds would be attracted to, much less consume, the bait 

in its form of use.

 On an acute basis, lufenuron was practically non-toxic to mammals as judged by toxicity 

testing of mice and rats. Because reproductive tests were not provided, it was not possible 

to estimate the chronic toxicity of lufenuron to mammals.

b. Drinking Water Exposure Assessments

As part of EFED’s assessment of lufenuron in 2004, drinking water exposures were considered 

likely to be low and not likely to exceed the known water solubility of 60 μg/L (60 ppb) at 25°C. 

Additionally, because of lufenuron's high affinity to sorb to sediment and organic material, its 

removal by flocculation/coagulation followed by sedimentation and/or filtration in the drinking 

water treatment process was considered likely, but not quantifiable.

c. Clean Water Act Programs

Lufenuron is not identified as a cause of impairment for any water bodies listed as impaired under 

section 303(d) of the Clean Water Act. No Total Maximum Daily Load (TMDL) criteria have 

been developed for lufenuron. Aquatic benchmarks have not been established for lufenuron.

5. Environmental Fate and Transport

The environmental fate assessment of lufenuron is based on its physical/chemical properties and a 

limited number of laboratory studies (hydrolysis, batch-equilibrium adsorption/desorption). A

selection of physical, chemical, and environmental fate and transport properties of lufenuron is 

summarized in Table 3.

Lufenuron is stable to abiotic hydrolysis. Lufenuron is assumed to be stable to aerobic and 

anaerobic microbially-mediated degradation, an assumption that is supported by results from a 

soil metabolism study rendered invalid as part of the 2004 ecological risk assessment (DP293833, 

DP295519). Based on its vapor pressure, lufenuron is not expected to volatilize from soil or 

water. Lufenuron's low solubility in water (60 μg/L) , high soil-water partition coefficient (Kds 

ranging from 166 to 2,350 L/kg) and predicted slight mobility in soil indicate that lufenuron will

not substantially dissolve in moisture that may enter termite bait stations, so the potential for

the chemical leaching from the bait stations is expected to be low. Any lufenuron that does

leach from bait stations is expected to bind readily to most soils. Because of its low mobility 

potential, lufenuron is not expected to leach to groundwater or reach surface water as a solute in 

runoff. 

Based on its log KOW of 5.12, lufenuron is a hydrophobic (lipophilic) chemical and, therefore, has 

the potential to bioaccumulate. However, due to lufenuron’s unique use pattern, its 

physical/chemical properties, and its high sorption potential (soil-water partition coefficients), 
7

bioaccumulation potential is expected to be limited to termites and possibly ground-feeding 

insectivorous terrestrial vertebrates.

Table 3. Physical/Chemical Properties and Environmental Fate Parameters of Lufenuron

Parameter Value Description Source

Selected Physical/Chemical Parameters

Molecular mass 511.2 g/mol -- EPI Suite

Vapor pressure (25°C) < 3.0 x 10-8torr Not expected to be 

volatile under field 

conditions

MRID 45839503

Aqueous solubility (25C) 60 μg/L Low solubility MRID 45839503

Henry’s Law Constant (25C) < 3.4 x 10-7

atm-m3/mol Not expected to be 

volatile from water

Estimated from 

water solubility 

and vapor pressure

Dissociation Constant (pKa)

(20C)

10.2 MRID 45839503

Log octanol-to-water partition 

coefficient

(log KOW and log POW) (25C)

5.12 Hydrophobic EPI Suite and 

MRID 45839503

Persistence

Hydrolysis half-life (25C) pH 5: stable 

pH 7: stable

pH 9: stable

MRID 45853201

Mobility

Soil-water partition coefficients 

(KD); organic carbon-normalized 

coefficients (KOC)

166, 321, 1,963, 2,350 

L/kg;

11,888, 12,117, 44,714, 

62,357, 74,833 L/kgOC

Immobile MRID 45853203

a. Transformation Products

In the one acceptable study submitted for lufenuron, hydrolysis, no major transformation products 

(i.e., transformation products >10%) were formed at the environmentally relevant temperature 

tested (25C). 

6. Receptors

Table 4 provides a summary of the terrestrial vertebrate toxicity data to characterize the potential 

acute and chronic ecological effects of lufenuron. 
8

Table 4. Summary of the Most Sensitive Endpoints from Terrestrial Vertebrate Toxicity Studies 

for Lufenuron

Taxonomic 

Group

Study 

Type

Surrogate 

Species

Toxicity Value

(all units in terms 

of measured active 

ingredient)

Acute 

Toxicity 

Classification

Source 

Birds1

Acute

Bobwhite quail

(Colinus 

virginianus)

LD50 >2000 mg/kgbwPractically 

Non-Toxic

45853215

Acceptable

Sub-acute 

dietary

Bobwhite quail

(Colinus 

virginianus)

LC50 > 5000 mg/kgdiet

Body Weight Gain:

NOAEC = 315 

mg/kg-diet

Practically 

non-toxic

45853213

Acceptable

Chronic

Bobwhite quail

(Colinus 

virginianus)

NOAEC = < 200

ppm

LOAEC = 200 ppm

--

45853215

Supplemental

Mammals

Acute Oral

Laboratory rat 

(Rattus 

norvegicus)

LD50 > 2000 mg/kgbwPractically 

non-toxic

45810301

Acceptable

Chronic

Laboratory rat 

(Rattus 

norvegicus)

Maternal NOAEL = 

500 mg/kg/day

Maternal LOAEL = 

1000 mg/kg/day

Endpoint: decreased 

body weight gain 

and food 

consumption

--

45853219

Acceptable

1 Birds represent surrogates for terrestrial-phase amphibians and reptiles.

Toxicity to Birds

In the acute avian oral toxicity tests for the mallard duck (MRID 45853210) and bobwhite quail

(MRID 45853211), no mortality was observed even in the highest treatment groups of 2000 mg

a.i./kg- body weight. Therefore, lufenuron is classified as “practically non-toxic” on an acute oral

basis. Based on current data requirements in 40 CFR Part 158, an acute oral toxicity study in a 

passerine bird is recommended to be requested. This study is of particular importance because 

the insectivorous birds most likely to be exposed to lufenuron via termite ingestion would be 

passerines. 

In the subacute dietary tests for the mallard duck (MRID 45853212) and bobwhite quail

(MRID 45853213), mortality was observed at the highest treatment levels in both tests. In both

cases, however, the LC50 was greater than the highest tested level. In each test, sublethal effects 

were observed. In the duck study, reduced feed consumption was observed at the 5020 mg/kgdiet. Therefore, the NOEC was 2480 mg/kg-diet. In the bobwhite quail study, data at the 618 

mg/kg-diet level were compromised, but statistically meaningful reductions in body weight gain 

were seen in all higher treatment categories. Consequently, the NOEC was 315 ppm a.i. (diet). 

The quail study suggests lufenuron is slightly toxic to some birds; however, the classification 

would be “practically non-toxic” based on the endpoint.
9

Two avian chronic reproductive studies were also provided, MRID 45853214 for the mallard 

duck and MRID 45853215 for the bobwhite quail. The duck study was classified as invalid based 

on unusually high, but unexplained chick mortality in each group during weeks 17 and 18 of the 

study. In the quail study, no statistically significant treatment related effects were observed in the 

adult animals. Reductions were seen in hatchling survival, proportion of 14 day survivors of 

normal hatchlings, hatchling survival per egg set, and hatchling weight. Hatchling survival for

normal hatchlings was the most sensitive endpoint with statistically significant reductions at all

treatment levels. Based on this result, a NOEC could not be established and is less than the lowest 

tested level of 200 ppm. Because of the potential for dietary exposure of ground-feeding birds via 

termite ingestion, additional chronic reproductive studies are recommended to be requested for 

both upland game and waterfowl.

Toxicity to Mammals

In most cases, mammalian toxicity data from the Health Effects Division (HED) are used to 

approximate toxicity to wild mammals. However, wild mammal toxicity tests may be required on 

a case-by-case basis, depending on the results of the lower tier studies such as acute and sub-acute 

testing, intended use pattern, and pertinent environmental fate characteristics. For the purposes of 

this problem formulation and the risk assessment to be conducted under registration review, 

available mammalian toxicity data on laboratory mammals will be used in the absence of toxicity 

data on mammalian wildlife.

In general, available toxicity tests indicate lufenuron is “practically non-toxic” to mammals 

exposed for short periods (e.g., the acute oral limit LD50 dose of 2000 mg/kg; MRIDs 45810301 

and 45853216). In the acute oral study with mice (MRID 45853216) there was no mortality, 

however clinical signs of neurotoxicity were observed during the study. The animals showed

piloerection, hunched posture, and dyspnea. There were no treatment related changes in body

weights during the study and no gross abnormalities were noted at necropsy. In the other acute

oral study with rats (MRID 45810301) no animals died during the study. Clinical abnormalities

included exophthalmos, hunched posture, dyspnea and ruffled fur. Lufenuron had no effect on

body weight gain and no abnormalities related to the test material were observed at necropsy.

There is currently no 2-generation rat study available for lufenuron. In the available 

developmental study with rats there were effects at larger doses (e.g., the maternal LOAEL of 

1000 mg/kg/day was based on decreased body weight gain and food consumption and the

maternal NOAEL was 500 mg/kg/day; the developmental NOAEL was >1,000 mg/kg/day and the 

developmental LOAEL was not determined; MRID 45853219). In the prenatal developmental

study with non-rodents (MRID 45853218), the maternal NOAEL and developmental NOAEL

were >1000 mg/kg/day; the LOAELs were not achieved. 

a. Ecological Incidents

A search of the Ecological Incident Information System (EIIS), the Incident Data System (IDS) 

and the Avian Incident Monitoring System (AIMS) databases did not result in reported incident 

data, as expected for a chemical with no reported usage in the United States. 
10

7. Exposure Pathways of Concern

Dietary exposure to ground-feeding insectivorous terrestrial vertebrates through the consumption 

of termites that have fed on bait will be the only exposure pathway of concern considered in the 

ecological risk assessment. 

Based on lufenuron’s application method (i.e., bait station), its physical and chemical properties, 

and its environmental fate and transport characteristics, the likelihood that, with the exception of 

ground-feeding insectivorous terrestrial vertebrates, non-target organisms will have direct contact 

with lufenuron is considered extremely low. Additionally, foraging habits (i.e., use of cellulose

materials as food) and the placement locations of the bait station (i.e., residential and urbanized

areas) reduce the likelihood that native ground-dwelling bees and non-target terrestrial 

invertebrates that would come into contact with lufenuron. 

With regard to exposures to aquatic non-target organisms, the following end use product labels 

have precautionary language that further reduce the likelihood of lufenuron residues migrating to 

surface water:

 Reg. No. 100-1181: “Do not apply directly to water, or to areas where surface water is 

present, or to intertidal areas below the mean high water mark.”

 Reg. No. 100-1175: “This product is toxic to fish and aquatic invertebrates. Do not 

discharge effluent containing this product into lakes, streams, ponds, estuaries, oceans, or 

other waters unless in accordance with the requirements of a National Pollutant Discharge 

Elimination System (NPDES) permit and the permitting authority has been notified in 

writing prior to the discharge. Do not discharge effluent containing this product to sewer 

systems without previously notifying the local sewage treatment plant authority. For 

guidance contact your State Water Board or Regional Office of the EPA. Do not 

contaminate water when disposing of equipment wash water.”

8. Analysis Plan

a. Stressors of Concern

i. Ecological Risk Assessment

Lufenuron parent is considered the only stressor of ecological concern for non-target organisms.

ii. Drinking Water 

Based on lufenuron’s application method (i.e., bait station), its physical and chemical properties, 

and its environmental fate and transport characteristics, the likelihood that lufenuron will be 

present in drinking water is considered extremely low. 
11

b. Measures of Exposure 

As a conservative measure, the ecological risk assessment will assess exposures of terrestrial

vertebrates to lufenuron through consumption of contaminated termites by estimating the quantity 

(mass) of lufenuron per termite and deriving dietary-based exposure concentrations and dosebased exposure estimates. The risk assessment will consider data from other insect growth 

regulator compounds. For example, use of data submitted for hexaflumuron, a chemical from the 

same class with a similar use pattern, would return chronic risk quotients of approximately 3 

(USEPA 2014).

Using a representative termite body weight of 3 mg (Zhou et al. 2008), the measured pesticide

mass per termite would be converted to a concentration basis (i.e., mg lufenuron/kg termite). 

This value would be used as the dietary-based EEC and would also be used to derive dose-based

EECs for terrestrial animals potentially consuming termites using allometric equations intended

to estimate food intake rates for small-, medium- and large-sized mammals and birds (USEPA

1993). 

The following equations will be used to determine the food intake (FI) for ground-feeding 

insectivorous birds and mammals:

• Avian consumption: FI = (0.648 * BW0.651) / (1 - W)

• Mammal consumption: FI = (0.621 * BW0.564) / (1 - W)

where:

FI = food intake in grams per day

BW = body mass of animal (avian: 20 g, 100 g, 1000 g; mammal: 15 g, 35 g, 1000 g)

W = mass fraction of water in the food (0.8 for insectivores)

To calculate the dose-based EECs for birds and mammals, the following equation will be used:

 Avian/Mammal Dose-Based EECs: [(D* FI)/BW]

where:

D = dose of lufenuron in milligrams per kilogram of termites

FI = food intake in grams per day

BW = body mass of animal (avian: 20 g, 100 g, 1000 g; mammal: 15 g, 35 g, 1000 g)

i. Available Monitoring Data

The Agency is not aware of any monitoring conducted by federal and state agencies to consider in 

the ecological risk assessment for registration review of lufenuron.
12

c. Measures of Effect 

Toxicity data submitted by the registrant under registration review as well as data presented in 

Section 3 of this problem formulation will be used to calculate risk quotients. Any additional 

information submitted by the registrant or found in the open literature prior to conduct of the risk 

assessment will also be considered. The open literature studies are identified using EPA’s 

ECOTOXicology database (ECOTOX) (USEPA 2007), which employs a literature search engine 

for locating chemical toxicity data for aquatic life, terrestrial plants, and wildlife. The evaluation 

of both sources of data can also provide insight into the direct and indirect effects of pesticides on 

biotic communities from loss of species that are sensitive to the chemicals and from changes in 

structure and functional characteristics of the affected communities.

9. Endangered Species Assessments

Consistent with EPA’s responsibility under the Endangered Species Act (ESA), the Agency will 

evaluate risks to federally listed threatened and endangered (listed) species from registered uses of 

pesticides in accordance with the Joint Interim Approaches developed to implement the 

recommendations of the April 2013 National Academy of Sciences (NAS) report, Assessing Risks 

to Endangered and Threatened Species from Pesticides. The NAS report outlines 

recommendations on specific scientific and technical issues related to the development of 

pesticide risk assessments that EPA and the Services must conduct in connection with their 

obligations under the ESA and FIFRA. EPA will address concerns specific to lufenuron in 

connection with the development of its final registration review decision for lufenuron. 

In November 2013, EPA, the U.S. Fish and Wildlife Service, National Marine Fisheries (the 

Services), and USDA released a white paper containing a summary of their joint Interim 

Approaches for assessing risks to listed species from pesticides. These Interim Approaches were 

developed jointly by the agencies in response to the NAS recommendations, and reflect a 

common approach to risk assessment shared by the agencies as a way of addressing scientific 

differences between the EPA and the Services. Details of the joint Interim Approaches are 

contained in the November 1, 2013 white paper, Interim Approaches for National-Level Pesticide 

Endangered Species Act Assessments Based on the Recommendations of the National Academy of 

Sciences April 2013 Report.

Given that the agencies are continuing to develop and work toward implementation of the Interim 

Approaches to assess the potential risks of pesticides to listed species and their designated critical 

habitat, this ecological problem formulation supporting the Preliminary Work Plan for lufenuron 

does not describe the specific ESA analysis, including effects determinations for specific listed 

species or designated critical habitat, to be conducted during registration review. While the 

agencies continue to develop a common method for ESA analysis, the planned risk assessment for 

the registration review of lufenuron will describe the level of ESA analysis completed for this 

particular registration review case. This assessment will allow EPA to focus its future evaluations 

on the types of species where the potential for effects exists, once the scientific methods being 

developed by the agencies have been fully vetted. Once the agencies have fully developed and 

implemented the scientific methods necessary to complete risk assessments for listed species and 

their designated critical habitats, these methods will be applied to subsequent analyses of 

lufenuron as part of completing this registration review.
13

10. Endocrine Disruptor Screening Program

Lufenuron was not included in the first group of 67 chemicals issued an order to conduct Tier 1 

EDSP testing, or the final second list of 109 chemicals identified for Tier 1 EDSP testing. For 

additional information on the EDSP program, visit http://www.epa.gov/endo/.

11. Preliminary Identification of Data Gaps 

a. Environmental Fate

Table 5 identifies environmental fate studies by MRID that have been submitted, as well as study 

classifications and whether or not further data are needed in order to support risk assessment.

Table 5. Submitted Environmental Fate Data for Lufenuron

OCSPP 

Guideline

Data 

Requirement

Submitted 

Studies 

(MRID)

Study 

Classifications

Are data 

needed to 

conduct risk 

assessment?

Justification and Assumptions EPA 

will Make in Absence of Data

835.2120 Hydrolysis 45853201 Acceptable No --

835.4100 Aerobic soil 

metabolism

45853202 Unacceptable No Assume lufenuron is stable to aerobic 

soil metabolism.

835.4200 Anaerobic soil 

metabolism

45853202 Unacceptable No Assume lufenuron is stable to anaerobic 

soil metabolism.

835.1230

835.1240

Adsorption/ 

desorption and 

leaching

45853203 Supplemental No --

45853204

45853205

b. Effects

Table 6 and Table 7 identify ecological effects studies by MRID that offer data for each 

guideline requirement, as well as study classifications and whether or not further data are needed 

in order to support risk assessment. Rationale for the additional data requested is presented below 

the tables.

Table 6. Submitted Aquatic Ecological Effects Data for Lufenuron

OCSPP

Guideline

Data 

Requirement

Submitted 

Studies 

(MRID)

Study 

Classifications

Are data 

needed for

risk 

assessment?

Comments

850.1010 Freshwater 

invertebrate 

acute toxicity

45853206 Invalid No --

850.1035

850.1045

Saltwater 

invertebrate 

acute toxicity 

45853207 Invalid No --

850.1075 Freshwater 

fish acute 

toxicity 

45853208 Invalid No --

45853209 Acceptable
14

Table 7. Submitted Terrestrial Ecological Effects Data for Lufenuron

OCSPP 

Guideline

Data 

Requirement

Submitted 

Studies 

(MRID)

Study 

Classifications

Are data 

needed for 

risk 

assessment?

Justification and Assumptions EPA 

will Make in Absence of Data

850.2100 Avian oral 

toxicity

45853210 Acceptable Yes An acute oral toxicity study with a 

passerine bird is needed to assess 

potential risk from lufenuron bait 

stations. In the absence of these data, 

risk to passerine species will be 

presumed.

45853211 Acceptable

850.2200 Avian dietary 

toxicity 

45853212 Acceptable No --

45853213 Acceptable

850.2300 Avian 

reproduction

45853215 Supplemental Yes An avian reproduction study in an 

upland game bird is needed, as a 

NOEC could not be determined from 

the submitted study. A waterfowl 

species is also needed to assess 

potential risk from lufenuron bait 

stations. In the absence of these data, 

risk will be presumed, and may be 

further explored by evaluating data 

from similar insect growth regulators.

45853214 Invalid

870.1100

Acute 

Mammalian 

Toxicity

45810301

45853216

Acceptable No

870.3700

Prenatal 

Developmental 

Toxicity Study

45853218

45853219

Acceptable No

850.3020

(Tier 1)

Honey bee 

adult acute 

contact 

toxicity

none none No Foraging habits and the placement 

locations of the bait station limit the 

exposure to lufenuron.

850.3030

(Tier 1)

Honey bee 

toxicity of 

residues on 

foliage

none none No Foraging habits and the placement 

locations of the bait station limit the 

exposure to lufenuron.

850.3040

(Tier 2 or 

3)

Field testing 

for pollinators

none none No Foraging habits and the placement 

locations of the bait station limit the 

exposure to lufenuron.

NonGuideline 

Study

(Tier 1) 

Honey bee 

adult acute 

oral toxicity

none none No Foraging habits and the placement 

locations of the bait station limit the 

exposure to lufenuron.

NonGuideline 

Study

(Tier 1)

Honey bee 

larvae acute 

oral toxicity

none none No Foraging habits and the placement 

locations of the bait station limit the 

exposure to lufenuron.
15

OCSPP 

Guideline

Data 

Requirement

Submitted 

Studies 

(MRID)

Study 

Classifications

Are data 

needed for 

risk 

assessment?

Justification and Assumptions EPA 

will Make in Absence of Data

NonGuideline 

Study 

(Tier 1)

Honey bee 

adult chronic 

oral toxicity

none none No Foraging habits and the placement 

locations of the bait station limit the 

exposure to lufenuron.

NonGuideline 

Study 

(Tier 1)

Honey bee 

larvae chronic 

oral toxicity

none none No Foraging habits and the placement 

locations of the bait station limit the 

exposure to lufenuron.

NonGuideline 

Study

(Tier 2)

Semi-field 

testing for 

pollinators 

(tunnel or 

colony feeding 

studies)

none none No Foraging habits and the placement 

locations of the bait station limit the 

exposure to lufenuron.

NonGuideline 

Study 

(Tier 2)

Field trial of 

residues in 

pollen and 

nectar

none none No Foraging habits and the placement 

locations of the bait station limit the 

exposure to lufenuron.

12. Bibliography

Committee on Ecological Risk Assessment Under FIFRA and ESA; Board on Environmental 

Studies and Toxicology; Division on Earth and Life Studies; National Research Council. 

2013. Assessing Risks to Endangered and Threatened Species from Pesticides. 

http://www.nap.edu/catalog/18344/assessing-risks-to-endangered-and-threatened-speciesfrom-pesticides

USEPA. 1993. Wildlife exposure factors handbook. Volume I of II. EPA/600/R-93/187a. Office 

of Research and Development, Washington, D.C. 20460.

USEPA. 2004. Overview of the Ecological Risk Assessment Process in the Office of Pesticide 

Programs. United States Environmental Protection Agency (USEPA). Environmental 

Fate and Effects Division. Office of Pesticide Programs. Available at 

http://www.epa.gov/espp/consultation/ecorisk-overview.pdf.

USEPA. 2007. Pesticide ECOTOX database. http://cfpub.epa.gov/ecotox/quick_query.htm.

USEPA. 2014. Registration Review: Preliminary Risk Assessment and Endangered Species 

Effects Determination for Hexaflumuron. Office of Pesticide Programs. D405911.

USEPA, USFWS, USNMF, and USDA. 2013. Interim Approaches for National-Level Pesticide 

Endangered Species Act Assessments Based on the Recommendations of the National 

Academy of Sciences April 2013 Report. http://www.epa.gov/espp/2013/interagency.pdf

Zhou, X et al. 2008. RNA interference in the termite Reticuliteremes flavipes through ingestion.