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

Ros anna 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 Wat er 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 Assessme nts

................................ ................................ ...................... 12

10. Endocrine Disruptor Screening Program

................................ ................................ ....... 13

11. Preliminary Identification of Data Gaps

................................ ................................ ........ 13

a. Environmental Fate

................................ ................................ ................................ ............ 13

b. Effects

................................ ................................ ................................ ................................ 13

12. Bibliography

................................ ................................ ................................ ...................... 153



## 1. Executive summary

The Environmental Fate and Effects Division (EFED) has completed the preliminary problem formulation (attached) for the ecological risk and endangered species assessment s to be conducted as part of the registration review of l ufenuron. 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 addi tional studies that would be beneficial to the conduct of an ecological risk assessment.

In this p roblem f

ormulation, 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

. Additi onally, use of cellulose materials as the food

- based delivery

system and the placement within bait station s 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

, a nd is considered t he 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 p roblem f

ormulatio n 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 (term ites) 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 upla nd 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 a mount of product present in each bait station.

 Labels do not specify the maximum number of bait s tations 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 Identificat ion Information for Lufenuron

Chemical Name s 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: C 17 H 8 Cl 2 F 8 N 2 O 3

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 ba it 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 ter mite 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 pro ducts are not currently marketed or used in the United States.5

Lufenuron products are ready

- to

- u se, 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 above

gro und 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 d o not specif y 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 pro perties, 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.

Inve rt Fish BCF Aquatic

Inverts Aquatic

Plants Groundwate r Persist

- ence Degrad at e

of

Concern

No a b NA ac No? d NA a No ae No? a

d No ae 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; n o 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 inverteb rate LC50; i n 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 e ndangered 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 inv ertebrate 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 i s 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, fai led 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, lufen uron 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 pa rt of EFED’s assessment of lufenuron in 2004, d rinking 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, b ecause 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 luf enuron 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 as sumed 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 p ressure, lufenuron is not expected to volatilize from soil or

water. Lufenuron ' s low solubili t y in w a t er ( 60 μg/L)

, hi g h soil

- w a t e r p ar tition c o e ff i c i e nt (K d s ranging from 166 to 2,350 L/kg ) a nd p re di c t ed sli g ht mobili t y in soil i n di ca te th a t lufenuron will

not subst a nti a l l y d i ssolve in moistu r e th a t m a y e nt e r termite b a it st a tions, so the pot e nti a l f o r the c h e mi ca l l e ac hi n g from the b a it st a tions is e x p ec t e d to be low. A n y lufenuron th a t do e s l eac h f r om b a it st a tions is e x p ec t e d to bind rea di l y 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 K OW 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 ( s oil

- water partition coeffici ents )

,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 5 1 1. 2 g/mol

-- EPI Suite

Vapor pressure (25 °C) < 3.0 x 10

- 8 torr Not expected to be

volatile under field

conditions MRID 45839503

Aqueous solubility (25  C) 60 μ g/L Low s olub ility MRID 45839503

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

- 7 atm

- m 3 /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 K OW and log P OW ) (25  C) 5.12 Hydrophobic EPI Suite and

MRID 45839503

Persistence

Hydrolysis half

- life (2 5  C) pH 5: stable

pH 7: stable pH 9: stable MRID 45853201

Mobility

Soil

- water partition coefficients (K D ); organic carbon

- normalized coefficients (K OC ) 166, 321, 1,963, 2,350 L/kg ; 11,888, 12,117, 44,714, 62,357, 74,833 L/kg OC Immobile MRID 4 5853203



### 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 provide s 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 M ost S ensitive E ndpoints from T errestrial Vertebrate T oxicity S tudies

for Lufenuron

Taxonomic Group Study

Type Surrogate

Species Toxicity Value

(all units in terms

of measured active ingredient) Acute

Toxicity

Classification Source

Birds 1 Acute Bobwhite quail ( Colinus virginianus ) LD 50 >2000 mg/kg

bw Practically

Non

- Toxic 45853215

Acceptable

Sub

- acute dietary Bobwhite quail

( Colinus virginianus ) LC 50 > 5000 mg/kg

diet

Body Weight Gain:

NOAEC = 315 mg/kg

- diet Practically

non

- toxic 45853213

Acceptable

Chronic Bobwhite quail

( Colinus virginianus ) NO A EC = < 200

ppm LO A EC = 200 ppm -- 45853215 Supplemental

Mammals Acute Oral Laboratory rat ( Rattus norvegicus ) LD 50 > 2000 mg/kg

bw Practically

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 cla ss ified 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 insectivo rous 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 LC 50 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/kg

diet

. Therefore, the NOEC was 2480 mg/kg

- diet

. In the bobwhite quail study, data at the 

### 6 18 mg/kg

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

were seen in all higher treatment categorie s. Consequently, the NOEC was 3 15 pp m 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 i n 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 statis tically 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 pp m

. 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 pu rposes 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 toxicit y tests indicate lufenuron is “practically non

- toxic” to mammals exposed for short periods (e.g., the a cute oral limit LD 50 dos e of 2000 mg/kg; MRIDs 45810301

and 458532 16). In the acute or al study with mice (MRID 458532 16) 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 th e other acute oral study with rats (MRID 4581030 1) 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 tes t 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 decreas ed 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

stud y with non

- rodents (MRID 45853 218 

### ), 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 Av ian 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 co nsumption 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

. , b a it st a tion), its physical and chemical properties,

and its environment al 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. A ddition a l l y
, f o r a g i n g h a bits ( i. e

. , use of ce llulose

m a t er i a ls a s f

ood) a nd the pl ace m e nt lo c a tions of the b a it st a tion ( i. e

. , re sid e nti a l a nd u r b a ni z e d

area s ) re du c e the lik e lihood th a t n a tive g r ound

- d w e lling b e e s a nd non

- t ar g e t t er r e st r i a l

inv er t e br a t e s that would c ome into c o n t ac t with lufenuron.

With regard to exposures to aquatic non

- target organisms

, t he 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 int o 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 e quipment wash water.”



## 8. Analysis Plan

a. Stressors of Concern

i. Ecological Risk Assessment

Lufenuron parent is considered the only stressor of ecologic al concern for non

- target organisms

.

ii. Drinking Water

Based on lufenuron’s application method ( i. e

. , b a it st a tion), 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 c o ns er v a tive m ea s u re
, the ec ol o g i ca l r isk a ss e ssm e nt will assess e x posu re s of t er r e st r i a l

vertebrate s t o lufenuron th r o u gh c onsumption of c on t a min a t e d t er mit e s b y e stim a ting the qu a nti t y ( m a ss) of lufenuron p e r t e r mite a nd d er ivi n g d i e t a r y

- b a s e d e x posu r e c on ce nt r a tions a nd dos e

b a s e d e x posu r e e stim a t e s

. 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 (US EPA 2014).

Using a r e p re s e nt a tive t er mite bo d y w e i g ht of 3 mg ( Zhou e t al

. 2008 )

, the m ea su r e d p e sti c ide

m a ss p e r t e r mite would be c onv er t e d to a c on c e nt ra t ion b a sis ( i.e.

, m g lufenuron /kg t er mit e )

. T his v a lue would be us e d as the di e t a r y

- b a s e d EEC a nd would also be us e d to d er ive dos e

- b a s e d

EE C s f or t erre st r i a l a nim a ls pot e nti a l l y c on s uming t er mit e s using a l lom e t r ic e qu a tions int e nd e d

to e stim a te f

ood int a ke ra t e s f

o r sm a ll

- , m e dium

- a nd l a r g e

- si z e d m a mm a ls a nd bi r ds ( U S E P A

1993 )

.

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

- feeding

insectivorous birds and mammals:

• A v i a n c o n s u m p t i o n: F I = (0.64 8 * B W

0

. 651 ) / ( 1

- W

)

• M a mm a l c o n su m p t i o n: F I = (0.6 2 1 * B W

0

. 564 ) / ( 1

- W

)

w h e r e:

F I = f oo d i n ta k e in g r a m s p er d ay

B W = bo d y m a s s o f a n i m al ( a v ia n : 2 0 g
, 10 0 g
, 1 0 0 0 g ; m a m m al: 1 5 g
, 3 5 g
, 10 0 0 g )

W = m a s s f

r acti o n o f w ater i n t h e f

oo d (0. 8 f o r i ns ecti v or e s )

T o calc u late t h e do s e

- b a s ed EE C s f o r b i rd s a n d m a m m al s
, t h e f o ll o w i n g e q u ati o n will be u s e d:

 Avian/Mammal Dose

- Based EECs: [( D * FI ) /B W ]

w h e r e :

D = do s e o f lufenuron i n m il l i g r a m s p er k il o g r a m o f te r m it e s

F I = f oo d i n ta k e in g r a m s p er d ay

B W = bo d y m a s s o f a n i m al ( a v ia n : 2 0 g
, 10 0 g
, 1 0 0 0 g ; m a m m al: 1 5 g
, 3 5 g
, 10 0 0 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 us ed to calculate risk quotients. Any additional information submitted by the registrant or found in the open literature prior to conduct o f 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 chemical s and from changes in

structure and functional characteristic s 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 Threat ened 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 th e 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

Servi ces), 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 Approac hes 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 ef fects 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 o f 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 m ethods 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 wil l 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 fa te 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 E PA

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 guid eline 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 A qu atic E cological E ffects D ata 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 Acceptable14

Table 7

. Submitted Terrestrial E cological E ffects D ata 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 458532 10 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. 458532 11 Acceptable

850.2200 Avian dietary

toxicity 458532 1 2 Acceptable No

--

458532 13 Acceptable

850.2300 Avian

reproduction 458532 15 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. 458532 14 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 F oraging 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 F oraging 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 F oraging habits and the placement

locations of the bait station limit the

exposure to lufenuron

.

Non

Guideline Study (Tier 1) Honey bee

adult acute oral toxicity none none No F oraging habits and the placement

locations of the bait station limit the

exposure to lufenuron

.

Non

Guideline Study (Tier 1) Honey bee

larvae acute oral toxicity none none No F oraging 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

Non

Guideline Study (Tier 1) Honey bee

adult chronic oral toxicity none none No F oraging habits and the placement

locations of the bait station limit the

exposure to lufenuron

.

Non

Guideline Study (Tier 1) Honey bee

larvae chronic oral toxicity none none No F oraging habits and the placement

locations of the bait station limit the

exposure to lufenuron

.

Non

Guideline Study (Tier 2) Semi

- field

testing for pollinators (tunnel or colony feeding studies) none none No F oraging habits and the placement

locations of the bait station limit the

exposure to lufenuron

.

Non

Guideline Study (Tier 2) Field trial of

residues in pollen and

nectar none none No F oraging habits and the placement

locations of the bait station limit the

exposure to lufenuron

.



## 12. Bibliography

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. 2013. Assessing Risks to Endangered and Threatened Species from Pesticides. http://www.nap.edu/catalog/18344/assessing

- risks

- to

- endangered

- and

- threatened

- species

from

- pesticides

USEPA. 1993. Wildlife exposure f actors 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

.