Etofenprox (also Ethofenprox) Summary Document

Registration Review: Initial Docket

August 2007

Case Number 7407

		     Approved by: _____________________

    				        Peter Caulkins, Ph.D.

				        Acting Director

				        Special Review and Reregistration Division

				Date:	___________________

				TABLE OF CONTENTS

										Page #

Preliminary Work Plan (PWP)…………………………3

Fact Sheet………………………………………………...7

Ecological Risk Assessment Problem Formulation……10

Human Health Effects Scoping Document……………..26

Glossary of Terms and Abbreviations………………….32

PRELIMINARY WORK PLAN

Etofenprox

Introduction

Amendments to the Federal Fungicide Insecticide and Rodenticide Act
(FIFRA) in the Food Quality Protection Act of 1996 mandated a new
program: Registration Review.  All pesticides distributed or sold in the
United States must be registered by the U.S. Environmental Protection
Agency (the Agency), after an assessment of scientific data shows that
they will not cause unreasonable risks to human health or the
environment when used as directed on product labeling.  The Agency’s
understanding of the potential for adverse effects from use of a
pesticide can evolve, because changes in science, public policy, and
pesticide use practices will occur over time.  The new registration
review program is intended to make sure that, as the ability to assess
and reduce risk evolves and as policies and practices change, all
registered pesticides continue to meet the statutory standard of no
unreasonable adverse effects.  Information on this program is provided
at: http://www.epa.gov/oppsrrd1/registration_review/.

This document opens the first reevaluation of etofenprox under
Registration Review.  The Agency plans to review each registered
pesticide every 15 years to determine whether it continues to meet the
FIFRA standard for registration.  The public phase of registration
review begins when the initial docket is opened for each case.  The
docket is the Agency’s opportunity to state clearly what it knows
about the pesticide and what additional risk analyses and data or
information it believes are needed to make a registration review
decision.  After reviewing and responding to comments and data received
in the docket during this initial comment period, the Agency will
develop and commit to a final work plan and schedule for registration
review of etofenprox.

Anticipated Risk Assessment and Data Needs

The Agency anticipates conducting an additional ecological risk
assessment under registration review that will include an assessment of
potential risk to endangered and threatened species (“listed
species”) in a manner consistent with agreements between the Agency
and the U.S. Fish and Wildlife Service and the National Marine Fisheries
Service (‘the Services”).  Please refer to Section III of this
document, Ecological Risk Assessment Problem Formulation, for a detailed
discussion of the anticipated ecological risk assessment needs. The
Agency also expects to conduct an additional human health risk
assessment.

	Ecological Risk

A screening level ecological risk assessment has been conducted for
etofenprox.  The most recent assessment for etofenprox was completed
September 20, 1999.  Also, there have been two previous Section 18 risk
assessments for use on rice in Louisiana completed March 16, 2006 and
January 31, 2007.

The Agency foresees needing additional ecotoxicity studies prior to
conducting the planned assessments; however, the Agency is aware that a
full suite of ecotoxicity studies has been submitted and review of these
data is awaiting assessment of the pending Section 3 use on rice, which
should occur in 2008.  Should these studies be acceptable, the Agency
does not foresee the need for additional ecotoxicity data.

Based on the preliminary exposure estimates, previous risk assessment
endpoints, and assumptions discussed in Section III (“Registration
Review – Preliminary Problem Formulation for the Ecological Risk
Assessment of Etofenprox” July 25, 2007), risks (due to direct effects
from acute exposure) are possible to listed aquatic invertebrates.  The
available data for the assessment of acute risk to aquatic animals is
currently limited to freshwater species (i.e., no guideline toxicity
data for estuarine/marine species are available for etofenprox).

Chronic exposures were not estimated for taxa other than mammals due to
lack of reviewed chronic toxicity data; however, should the submitted
ecotoxicity studies be acceptable, the Agency does not foresee the need
for additional ecotoxicity or environmental fate data.

No reviewed acute or chronic toxicity data are currently available for
aquatic or terrestrial plants; however, should the submitted ecotoxicity
studies be acceptable, the Agency does not foresee the need for
additional ecotoxicity or environmental fate data.  Although etofenprox
is described as an insecticide and is therefore not anticipated to cause
adverse effects to plants, data are needed to determine whether this is
the case or not.  Hence, risks to species in these taxa are presumed.

The Agency foresees needing additional environmental fate studies prior
to conducting the planned assessments; however, the Agency is aware that
a full suite of environmental fate studies have been submitted and
review of these data is awaiting assessment of the pending Section 3 use
on rice, which should occur in 2008.  Should these studies be
acceptable, the Agency does not foresee the need for additional data.
These environmental fate data are needed to adequately characterize the
environmental fate of etofenprox associated with the use as an outdoor
fogger.

The planned ecological risk assessment will allow the Agency to
determine whether etofenprox’s use has "no effect" or "may affect"
federally listed threatened or endangered species (listed species) or
their designated critical habitat.  If the assessment indicates that
etofenprox "may affect" a listed species or its designated critical
habitat, the assessment will be refined.  The refined assessment will
allow the Agency to determine whether use of etofenprox is “likely to
adversely affect” the species or critical habitat or "not likely to
adversely affect" the species or critical habitat.  When an assessment
concludes that a pesticide's use "may affect" a listed species or its
designated critical habitat, the Agency will consult with the U.S. Fish
and Wildlife Service and National Marine Fisheries Service (the
Services), as appropriate.

Human Health Risk

There are currently no Section 3 food uses for etofenprox; however,
there is a Section 18 food use on rice in Louisiana (February 8, 2007).
Time-limited tolerances for residues of etofenprox have been established
on rice grain and straw.  The Section 18 assessment indicates no risks
of concern.

Section 3 request for use on rice is currently pending and has a PRIA
date of November 2008.

Data are required for the pending Section 3 food use on rice and have
been submitted, but no new data are required for the currently
registered etofenprox uses.

The Agency anticipates the need for new risk assessments for scenarios
using a reassessed short-term incidental oral endpoint.

Timeline

EPA has created the following estimated timeline for the completion of
the etofenprox registration review.

Activities	Estimated Completion

Phase 1: Opening the docket

Open Public Comment Period for Etofenprox Docket  	August 2007

Close Public Comment Period 	November 2007

Phase 2:  Case Development

Develop Final Work Plan (FWP)	1st Q 2008

Open Public Comment Period for Preliminary Risk Assessments 	3rd Q 2010

Close Public Comment Period	4th Q 2010

Phase 3: Registration Review Decision

Open Public Comment Period for Proposed Reg. Review Decision 	1st Q 2011

Close Public Comment Period 	2nd Q 2011

Final Decision and Begin Post-Decision Follow-up	2011

Total (years)	4

Note:  The Agency reserves the option to issue a DCI or require the data
as a condition of registration for the pending Section 3 registration if
the data that are currently in-house and unreviewed are determined to be
inadequate.  If a DCI is issued, additional time to complete
registration review will be necessary.

Guidance for Commenters

The public is invited to comment on EPA’s preliminary registration
review work plan and rationale.  The Agency will carefully consider all
comments as well as any additional information or data provided in a
timely way prior to issuing a final work plan for the etofenprox case.

Through the registration review process, the Agency intends to solicit
information on typical use patterns, state or local restrictions,
incidents, monitoring data, and environmental fate and toxicity data.
There are currently no Section 3 food uses for etofenprox; however,
there is a Section 18 food use on rice in Louisiana.  Time-limited
tolerances for residues of etofenprox have been established on rice
grain and straw.  The Section 18 assessment indicates no risks of
concern.

Etofenprox is not identified as a cause of impairment for any water
bodies listed as impaired under section 303(d) of the Clean Water Act,
based on information provided at   HYPERLINK
"http://oaspub.epa.gov/tmdl/waterslist.impairments"
http://oaspub.epa.gov/tmdl/waterslist.impairments .  The Agency invites
submission of water quality data for this pesticide.  To the extent
possible, data should conform to the quality standards in Appendix A of
the “OPP Standard Operating Procedure: Inclusion of Impaired Water
Body and Other Water Quality Data in OPP’s Registration Review Risk
Assessment and Management Process” (see:
http://www.epa.gov/oppfead1/cb/ppdc/2006/november06/session1-sop.pdf ),
in order to ensure they can be used quantitatively or qualitatively in
pesticide risk assessments.

There are currently no Section 3 food uses for etofenprox; therefore no
trade irritant issues due to differing tolerance and maximum residue
levels in different countries are expected.  The public is invited to
comment on any trade concerns.

Stakeholders are specifically asked to provide information and data in
the following areas:

typical use patterns for the yard and patio fogger

typical sites of application

duration of spray events

any information regarding the potential for drift

maximum application rates

annual frequency of application, date of initial application per year,
application intervals, and maximum number of applications per year

any geographic limitations on use

state or local use restrictions

ecological incidents (non-target plant damage and avian, fish,
reptilian, amphibian and mammalian mortalities) not already reported to
the Agency

monitoring data

environmental fate and toxicity data on any etofenprox degradates of
concern that may be identified

Next Steps

After the comment period closes, the Agency will prepare a Final Work
Plan for this pesticide.

II. FACT SHEET

Background Information

Etofenprox (also known as Ethofenprox) Registration Review Case Number:
7407

Etofenprox PC Code:  128965, CAS#:  80844-07-1

Technical Registrant:  Mitsui Chemicals America, Inc.

One technical product, and twenty-two end-use products (end-use products
contain other active ingredients—MGK 264, piperonyl butoxide,
prallethrin, pyriproxyfen, and pyrethrins) are currently registered.

First product (EPA reg. #: 33657-6) registered on September 14, 2001.

Not subject to reregistration; thus, no Reregistration Eligibility
Decision (RED) is available.

Special Review and Reregistration Division (SRRD), Chemical Review
Manager (CRM):  Sherrie Kinard,   HYPERLINK
<EMAIL_ADDRESS><EMAIL_ADDRESS>
Registration Division (RD), Product Manager (PM):  George Larocca,
HYPERLINK<EMAIL_ADDRESS><EMAIL_ADDRESS>
Use & Usage Information (For additional details, please refer to the
BEAD Appendix A document in the etofenprox docket.)

Etofenprox can be used as an insecticide as follows:

Spot treatment for cats;

Indoor and outdoor residential settings;

Non-food handling areas of commercial food-handling establishments;

Section 18 use on rice with a Section 3 use on rice pending (PRIA date:
November 2008);

Section 3 use as a mosquito adulticide is pending (PRIA date: August
2008).

Etofenprox is formulated as an emulsifiable concentrate, granular,
pressurized liquid, and a ready-to-use solution.

Etofenprox may be applied as a spray, fogger, or as a fumigant.

Recent Actions

An ecological risk assessment for a Section 18 use on rice in Louisiana
was completed January 31, 2007.

A health effects risk assessment for the etofenprox residential uses was
completed in April 2006 and an assessment for a Section 18 use on rice
in Louisiana was completed in February 2007.

Ecological Risk Assessment Status:  Please refer to Section III of this
document, Ecological Risk Assessment Problem Formulation, for a detailed
discussion of the anticipated ecological risk assessment needs.  Below
is a summary of the findings:

Avian acute oral toxicity tests indicate that etofenprox is practically
non-toxic to avian test species.

There are no registrant-submitted studies that have been reviewed for
etofenprox that address chronic toxicity to taxa other than mammalian;
however, the Agency is aware that a full suite of ecotoxicity studies
have been submitted and review of these data is awaiting assessment of
the pending Section 3 use on rice, which should occur in 2008.  Should
these studies be acceptable, the Agency does not foresee the need for
additional ecotoxicity data.

There are no registrant-submitted studies that have been reviewed for
etofenprox that address acute or chronic toxicity for aquatic and
terrestrial plants however, the Agency is aware that a full suite of
ecotoxicity studies have been submitted and review of these data is
awaiting assessment of the pending Section 3 use on rice, which should
occur in 2008.  Should these studies be acceptable, the Agency does not
foresee the need for additional ecotoxicity data.

Based on these preliminary exposure estimates, previous risk assessment
endpoints, and the assumptions discussed in Section III, risks (due to
direct effects from acute exposure) are possible to listed aquatic
invertebrates.  The potential for direct adverse effects as a result of
chronic exposures were not estimated for taxa other than mammals because
toxicity data have not been reviewed.

Before the risk assessments are developed for public comment, the Agency
will ensure that all currently registered uses of etofenprox have an
endangered species assessment completed.  The ecological risk assessment
will allow the Agency to determine whether etofenprox use has "no
effect" or "may affect" federally listed threatened or endangered
species (listed species) or their designated critical habitat.  If the
assessment concludes that a pesticide's use "may affect" a listed
species or its designated critical habitat, the Agency will consult with
the U.S. Fish and Wildlife Service and National Marine Fisheries Service
(Services), as appropriate.

Human Health Risk Assessment Status:  Please refer to Section IV of this
document, Human Health Effects Scoping Document, for a detailed
discussion of the anticipated risk assessment needs for human health.
Below is a summary of the findings:

Dietary (Food and Water):

There are currently no Section 3 food uses for etofenprox; however,
there is a Section 18 food use on rice in Louisiana.  Time-limited
tolerances exist for rice grain and straw.  The Section 18 assessment
indicates no risks of concern.

A Section 3 use on rice is pending.

Residential

Assessments completed on etofenprox indicate that residential exposure
scenarios did not result in risks of concern.  No new data will be
required; however, the Agency anticipates the need for new residential
risk assessments for scenarios using a reassessed short-term incidental
oral endpoint.

Occupational

Assessments completed on etofenprox indicate that occupational scenarios
did not result in risks of concern.  No new data will be required;
however, the Agency anticipates the need for new occupational risk
assessments using a reassessed short-term incidental oral endpoint.

Data Call-In (DCI) Status

No outstanding DCIs; however, the Agency reserves the option to issue a
DCI or require the data as a condition of registration for the pending
Section 3 registration if the data that are currently in-house and
unreviewed are determined to be inadequate.

Tolerances

No tolerances are required at this time since there are currently no
registered Section 3 food uses; however, time-limited tolerances for the
Section 18 etofenprox use on rice in Louisiana are established on rice
grain and straw.

A Section 3 use on rice is pending.

Labels

A list of registration numbers is included below and the labels can be
obtained from the Pesticide Product Label System (PPLS) website:
HYPERLINK "http://oaspub.epa.gov/pestlab1/ppls.home"
http://oaspub.epa.gov/pestlab1/ppls.home .

Etofenprox Registrations

Registration Number	Product Name	Company 	Active Ingredient

69332-4	Pl #1001 Etofenprox Spot-On	Pet Logic, L.L.C.	55

69332-3	Spi #8208-55d	Pet Logic, L.L.C.	55

33657-37	Premium Roach Spray	Mitsui Chemicals America, Inc.	1

33657-36	Crawling Insect Killer I	Mitsui Chemicals America, Inc.	1

33657-35	Flying Insect Killer II	Mitsui Chemicals America, Inc.	0.5

33657-34	Yard And Patio Fogger	Mitsui Chemicals America, Inc.	0.5

33657-9	1% Etofenprox Aerosol	Mitsui Chemicals America, Inc.	1

33657-8	1% Etofenprox Fogger	Mitsui Chemicals America, Inc.	1

33657-7	Etofenprox 3 Emulsifiable Concentrate	Mitsui Chemicals America,
Inc.	32.5

33657-6	Technical	Mitsui Chemicals America, Inc.	97

2724-786	RF 2050 Spray	Wellmark International	0.5

2724-705	Etofenprox IGR Fogger II	Wellmark International	0.5

2724-702	Etofenprox IGR Home & Carpet Spray II	Wellmark International
0.5

2724-701	Etofenprox IGR Home and Carpet Spray I	Wellmark International	1

2724-700	Etofenprox IGR Fogger I	Wellmark International	1

2724-699	Crawling Insect Killer II	Wellmark International	0.5

2724-677	Yard & Patio Fogger	Wellmark International	0.5

2724-675	Premium Roach Spray	Wellmark International	1

2724-668	Flying Insect Killer II	Wellmark International	0.5

2724-667	Crawling Insect Killer I	Wellmark International	1

2724-504	Rf2004 (Ccso)	Wellmark International	40

2724-EUP-48	NA	Wellmark International	100

06LA01	NA	LA Dept. of Agriculture & Forestry	NA

III. ECOLOGICAL RISK ASSESSMENT PROBLEM FORMULATION

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON D.C., 20460

August 16, 2007

	PC Code:  128965

	DP Barcode: 341891

MEMORANDUM

Subject:	Registration Review – Preliminary Problem Formulation for the
Ecological Risk Assessment of Etofenprox

To:		Anne Overstreet, Team Leader

		Sherrie Kinard, Chemical Review Manager

		Special Review Branch

		Special Review and Reregistration Division

From:		Christopher Salice, Biologist

		Greg Orrick, Environmental Scientist

		Environmental Risk Branch 4

		Environmental Fate and Effects Division

Through:	Elizabeth Behl, Chief

		Environmental Risk Branch 4

		Environmental Fate and Effects Division

Attached is the preliminary problem formulation for the ecological risk
assessment to be conducted as part of the Registration Review of the
insecticide etofenprox.

REGISTRATION REVIEW

ECOLOGICAL RISK ASSESSMENT PROBLEM FORMULATION FOR:

ETOFENPROX

2-(4-ethoxyphenyl)-2-methylpropyl 3-phenoxybenzyl ether

CAS Registry Number: 80844-07-1

PC Code: 128965

	Prepared by:

	Christopher Salice, Biologist

Greg Orrick, Environmental Scientist	U. S. Environmental Protection
Agency

Office of Pesticide Programs

Environmental Fate and Effects Division

Environmental Risk Branch IV

1200 Pennsylvania Ave., NW

Mail Code 7507P

Washington, DC 20460

Reviewed by:

Elizabeth Behl, Branch Chief

	BACKGROUND

The EFED etofenprox (also ethofenprox) Registration Review Team
evaluated the available environmental fate and ecotoxicity data and the
most recent assessments to determine the scope of work necessary to
support the registration review process for the use of etofenprox as an
outdoor fogger and as a spot treatment for pets (cats).  The primary
source for the scope of work was the most recent EFED assessment for
etofenprox (DP 259534, Sep. 20, 1999).  All sources reviewed during this
problem formulation are presented in Appendix B.

The purpose of this scoping effort is to determine whether sufficient
data are available to assess the potential risks of etofenprox use to
non-target organisms as well as to determine whether any new data have
been submitted since the last assessment that would necessitate
conducting a new ecological risk assessment in support of Registration
Review.

STRESSOR SOURCE AND DISTRIBUTION

Etofenprox [2-(4-ethoxyphenyl)-2-methylpropyl 3-phenoxybenzyl ether] is
a pyrethroid-like insecticide currently used as an indoor non-food crack
and crevice insecticide, a spot treatment for pets, and as an outdoor
fogger to control a variety of insect pests.  The labels for the yard
and patio fogger state that the product is only to be used in backyards,
patios, barns, picnic areas, and other areas where flying and crawling
insects are a problem.  The current patio fogger formulation is composed
of 0.50% etofenprox.  The spot treatment for pets is for use on cats and
contains up to 55% etofenprox.

Although there are a number of specified uses of etofenprox for use as
an indoor crack and crevice insecticide, exposures to non-target
wildlife and plants are not expected to occur as a result of these uses.
 Hence, this problem formulation quantitatively assesses for exposure
only the uses of the outdoor fogger and spot treatment for pets
formulations.

INTEGRATION OF AVAILABLE INFORMATION

The risk assessments that serve as the basis for this problem
formulation include the following (for details, see Appendix B):

One FIFRA Section 3 New Use (S3NU) assessment for indoor non-food crack
and crevice uses (DP 259534, Sep. 20, 1999)

Three FIFRA Section 18 risk assessments for use on rice in Louisiana or
Texas (DP 325107, Mar. 16, 2006; DP 335102, Jan. 31, 2007; DP 339676,
Jul. 17, 2007)

No EFED review was requested of the patio fogger use (registered Jan.
24, 2002) or the spot treatment for pets.  The Agency has received
applications for S3NUs including a mosquito adulticide use and a use on
rice.  Drinking water exposure and ecological risk assessments are
expected to be completed for these new uses by their PRIA due dates,
August, 2008 and November, 2008, respectively.

ECOLOGICAL EFFECTS

TOXICITY STUDIES

There are few available ecotoxicity data for etofenprox.  However, a
full suite of ecotoxicity studies have been submitted in support of the
upcoming Section 3 registration requests.  Thorough review of these
studies is pending.  Table 1 lists the currently available, reviewed
toxicity data for etofenprox.  Provisional data from several studies
were used prior to thorough review for several Section 18 requests for
use of etofenprox on rice.  Because these studies have not been
thoroughly reviewed, they are not included in Table 1, below.

Table 1.  Summary of Most Sensitive Ecotoxicity Endpoints for
Etofenprox.

Environment	Taxa	Exposure	Endpoints	Units	MRID

	Type	Value

Aquatic	Freshwater Fish	Acute	LC50	2.7	µg ai/L	436213-01

Chronic	No data

Freshwater Invertebrates	Acute	EC50	0.57	µg ai/L	404497-30

Chronic	No data

Plants	Acute	No data

	Terrestrial	Avian	Acute-oral	LD50	>2000	mg ai/kg-bw	404497-25

Acute-diet	LC50	>5000	mg ai/kg-diet	404497-26,-27

	Mammalian	Acute	LD50	>5000	mg ai/kg-bw	404497-24

Chronic	NOAEC	3.7	mg ai/kg/day	404497-13

	Plants	No data

Two acute toxicity tests on freshwater fish were reviewed for the
section 3 assessment.  The 96-hour LC50 for rainbow trout (MRID
436213-02) is 13.0 ppb.  Etofenprox is slightly more toxic to bluegill
sunfish (MRID 436213-01) with a 96-hour LC50 of 2.7 ppb.  Both studies
indicate that etofenprox is very highly toxic to freshwater fish on an
acute exposure basis.

An acute study on the freshwater invertebrate, Daphnia magna, resulted
in a 48-hour EC50 of 0.57 ppb (MRID 404497-30) which classifies
etofenprox as very highly toxic to aquatic invertebrates on an acute
exposure basis.

An avian acute oral toxicity test (MRID 404497-25) indicates that
etofenprox is practically non-toxic to Mallard ducks.  The estimated
LD50 is > 2000 mg/kg-bw (the highest concentration tested).  Two avian
subacute dietary toxicity tests also show that etofenprox is practically
non-toxic to avian test species.  For both the Northern bobwhite quail
(MRID 404497-26) and the mallard duck (MRID 404497-27), the LC50 > 5000
mg/kg-feed (the highest concentration tested).  No other avian toxicity
tests have been reviewed.

Toxicity studies reviewed by the Health Effects Division indicate that
on an acute exposure basis, etofenprox is practically non-toxic to
mammals with an LD50 > 5000 mg/kg-bw (the highest concentration tested).
 There are a number of longer-duration toxicity tests on mammals.  A
chronic dietary study indicated a NOAEL of 3.7 mg/kg-bw/day and a
corresponding LOAEL of 25.5 mg/kg-bw/day.  The endpoint chosen was
increased thyroid weight, which may or may not relate directly to
growth, survival, and reproduction.  For this review, we used HED’s
endpoints to evaluate the toxicity of etofenprox to mammals.  If future
assessments are required, the endpoints will be reviewed by EFED to
determine which are most appropriate for ecological receptors.

A full suite of ecotoxicity studies have been submitted to the Agency;
review of these studies is pending the Section 3 registration process.
If these toxicity studies are deemed ‘acceptable’, they will provide
a more comprehensive understanding of the toxicological effects of
etofenprox and will reduce uncertainties associated with assessing the
ecological risks of this pesticide.

INCIDENT REPORTS

The Agency has received no report of adverse field effects to non-target
animals or plants that have been attributed to the use of etofenprox.
The Agency also has no incident report from pesticide registrants
concerning etofenprox contamination of ground water or surface water.

A lack of reported incidents does not necessarily mean that such
incidents have not occurred.  In addition, incident reports for
non-target plants and animals typically provide information on mortality
events only.  Reports for other adverse effects, such as reduced growth
or impaired reproduction, are rarely received.

EXPOSURE CHARACTERISTICS

There are no reviewed environmental fate data for etofenprox.  A full
suite of studies on the fate characteristics of etofenprox have been
submitted in support of the upcoming Section 3 registration requests.
The reported vapor pressure and very low solubility of etofenprox, as
listed in the Section 3 assessment, suggest that vapor phase transport
to air may be an important loss mechanism for etofenprox.  Moreover,
because etofenprox is related to the synthetic pyrethroid class of
compounds, the compound likely has a strong potential for concentrating
in sediment if the compound should enter aquatic habitats.

Generally, because the only current relevant uses for ecological
receptors are the outdoor patio fogger and the pet spot treatment, EFED
does not expect etofenprox to reach levels in the environment likely to
cause adverse effects to non-target species.  This is based on the
assumption that, typically, use is restricted to a finite, relatively
small area near or within homes or businesses.  As such, the total
loading of etofenprox to nearby habitats is likely small.  However, in
the absence of suitable environmental fate data and typical use
patterns, conservative assumptions were made in this review to provide
some sense of the potential for adverse environmental effects.

CHARACTERISTICS OF ECOSYSTEMS POTENTIALLY AT RISK

For etofenprox and pesticides in general, the ecosystems at greatest
risk are those in close proximity to the use areas.  For the use of
etofenprox as an outdoor patio fogger, these would include terrestrial
habitats in close proximity to the use site and water bodies directly
adjacent to use sites that may receive chemical residues via drift,
runoff, and/or discharged ground water.  For the spot treatment use, the
ecosystems at greatest risk are water bodies that receive storm drainage
from nearby developments.  Within water bodies, the water column,
sediments, and pore water are all environmental compartments of concern.

Generally, organisms of concern include birds, mammals, reptiles, fish,
and terrestrial and aquatic invertebrates, plants, and amphibians.  The
assessment endpoints are intended to reflect population sustainability
and community structure within ecosystems and hence relate back to
ecosystems at risk.  If risks are expected for given species/taxa based
on the screening-level assessment, then risks might be expected to
translate to higher levels of biological organization.

ASSESSMENT ENDPOINTS

Assessment endpoints are defined as “explicit expressions of the
actual environmental value that is to be protected.”  Defining an
assessment endpoint involves two steps: 1) identifying the valued
attributes of the environment that are considered to be at risk; and 2)
operationally defining the assessment endpoint in terms of an ecological
entity (i.e., a community of fish and aquatic invertebrates) and its
attributes (i.e., survival and reproduction).  Therefore, selection of
the assessment endpoints is based on valued entities (i.e., ecological
receptors), the ecosystems potentially at risk, the migration pathways
of pesticides, and the routes by which ecological receptors are exposed
to pesticide-related contamination.  The selection of clearly defined
assessment endpoints is important because they provide direction and
boundaries in the risk assessment for addressing risk management issues
of concern.  Changes to assessment endpoints are typically estimated
from the available toxicity studies, which are used as the measures of
effects to characterize potential ecological risks associated with
exposure to a pesticide, such as etofenprox.

Typically, to estimate exposure concentrations, the ecological risk
assessment considers an application(s) at the maximum application rate
to use sites that have vulnerable soils.  Given the uses of etofenprox
as an outdoor fogger and a spot treatment, however, requires modified
approaches based on typified discharges from spray cans, foggers, and
pet treatments.  The most sensitive toxicity endpoints are used from
test species to estimate treatment-related direct effects on acute
mortality and chronic reproductive, growth and survival assessment
endpoints.  Toxicity tests are intended to determine effects of
pesticide exposure on birds, mammals, fish, terrestrial and aquatic
invertebrates, and plants.  The toxicity studies are used to evaluate
the potential of a pesticide to cause adverse effects, to determine
whether further testing is required, and to determine the need for
precautionary label statements to minimize the potential adverse effects
to non-target animals and plants.

CONCEPTUAL MODEL

The conceptual model is used to depict the potential exposure pathways
and effects associated with etofenprox use.  Through a preliminary
iterative process of examining use patterns and fate and effects data,
the conceptual model has been modified to reflect the exposure pathways
and the organisms for which risk is most likely.  Based on a preliminary
risk screening and past assessments indicating that etofenprox is highly
toxic to freshwater fish and invertebrates on an acute exposure basis
and causes potential reproductive effects in mammals when chronically
exposed, the hypothesis for the risks of etofenprox to non-target
animals (depicted in Figure 1) focuses on both aquatic and terrestrial
environments.  Therefore, exposure as a result of direct spray and
runoff will be considered.  Risk to terrestrial and aquatic plants is
also considered in this screening-level assessment.  For birds and
mammals, the major route of exposure considered is the dietary route;
consumption of food items such as plant leaves or insects that have
etofenprox residues as a result of spraying and drift.  Terrestrial
plants may be exposed via drift or runoff.  For aquatic animal species,
the major routes of exposure are considered to be via the respiratory
surface (gills) and/or the integument.  Aquatic plants may be exposed
via direct uptake and adsorption.

Estimated exposure concentrations for all organisms are obtained through
a simplified modification of current Agency approaches for estimating
exposure, which are designed more to address agricultural applications
of pesticides.  The modified approach is based on the maximum discharges
from a spray can or fogger and the treatment of an entire pet.  As such,
the total amount of etofenprox released to the environment is expected
to be low and localized to areas near the use site.

RISK HYPOTHESIS

Risk hypotheses are specific statements about potential adverse effects
(i.e., changes in assessment endpoints) and are tested using theory and
logic, empirical data, mathematical models, or probability models
(USEPA, 2004).  For this assessment, the risk is stressor-initiated,
where the stressor is the release of etofenprox to the environment.  The
following risk hypothesis is presumed for this screening level
assessment:

Based on the application methods, mode of action, and the sensitivity of
non-target aquatic and terrestrial species, etofenprox has the potential
to reduce survival, reproduction, and/or growth in terrestrial and
aquatic organisms.

In order for a chemical to pose an ecological risk, it must reach
non-target organisms at concentrations found to cause adverse effects.
The exposure pathway is the way by which a pesticide moves in the
environment from the application site to non-target organisms.  The
assessment of ecological exposure pathways in this assessment includes
an examination of the source and potential migration pathways for
etofenprox, and the determination of potential exposure routes to
non-target species.

DIAGRAM

Application methods for the use of etofenprox involve a manual yard and
patio fogger for use on insect pests near residences.  Ecological
receptors that may potentially be exposed to etofenprox include
terrestrial and semi-aquatic wildlife (i.e., mammals, birds, amphibians,
terrestrial invertebrates, reptiles, and plants).  In addition, aquatic
receptors (e.g., freshwater and estuarine/marine fish and invertebrates,
amphibians, and aquatic plants) may also be exposed as a result of
potential migration of etofenprox via spray drift and/or runoff from the
site of application to various watersheds and other aquatic
environments.  These data form the basis for identifying potential
endpoints, stressors, and ecological effects associated with etofenprox
fogger use (see Figure 1).

Use of etofenprox as a spot treatment for pets may result in
environmental concentrations of etofenprox in surface waters as a result
of washing pets after etofenprox has been applied.  Ecological receptors
that may potentially be exposed to etofenprox as a result of this
particular use are mostly limited to aquatic animals and aquatic and
semi-aquatic plants.  Figure 2 provides a representation of the
potential exposure routes and effects as a result of etofenprox use as a
spot treatment for pets.

Figure 1.  Conceptual model of the transport and effects of etofenprox
in the environment as a result of the outdoor fogger use.

*Dotted lines indicate that although this exposure route or pathway was
considered, it was not thought to contribute significantly to the fate
and transport of etofenprox.

Figure 2.  Conceptual model of the transport and effects of etofenprox
in the environment as a result of the spot treatment for pets.

ANALYSIS PLAN OPTIONS

In Registration Review, pesticide ecological risk assessments will
follow the Agency’s Guidelines for Ecological Risk Assessment, will be
in compliance with “Overview of the Ecological Risk Assessment Process
in the Office of Pesticide Programs, U.S. Environmental Protection
Agency” (“Overview Document”; USEPA, 2004), and will be conducted
in accordance with Section 7 of the Endangered Species Act.

A review of previously completed assessments indicates that assessments
of acute and chronic risk to non-target organisms have not been
completed for the outdoor fogger use or the spot treatment use; only the
inside crack and crevice uses were previously evaluated.  The conclusion
from that assessment was that etofenprox “should pose no risks to
terrestrial and aquatic organisms from the proposed indoor non-food use
pattern”.  This conclusion is based on the assumption that little, if
any, etofenprox is expected to reach the environment from indoor uses.

In emergency exemption (Section 18) risk assessments for etofenprox, the
risk conclusion included a potential for direct adverse effects to fish
and invertebrates.  These assessments were based on both reviewed and
provisional data and a use pattern that is characterized by direct
application of granules to rice paddy water.  Results from the Section
18 assessments are not directly applicable to the use of etofenprox as
an outdoor fogger.

 Furthermore, due to a lack of toxicity data, potential risks to
estuarine/marine organisms, aquatic vascular plants, and terrestrial
plants have not previously been assessed by the Agency.  Also, the
potential chronic risks to avian species have not been previously
assessed.

Appendix B shows the current status of risk assessments for registered
uses of etofenprox.  In addition to conducting screening level
assessments (and refined assessments, if necessary) for all etofenprox
uses, other uncertainties and potential paths forward are described
below.

The available reviewed data for the assessment of acute risk to aquatic
animals is currently limited to freshwater species (i.e., no guideline
toxicity data for estuarine/marine species are available for
etofenprox).  If the additional submitted toxicity data for
estuarine/marine species are not acceptable or are not located in the
open literature, and in the absence of information that would suggest
otherwise, we will assume that etofenprox is as toxic to
estuarine/marine species as it is to freshwater organisms.  Furthermore,
there are no reviewed data available for assessing the potential for
chronic risk to any aquatic species.  In the absence of acceptable data,
we will assume that etofenprox is toxic to aquatic species on a chronic
exposure basis.

No reviewed toxicity data are currently available for aquatic or
terrestrial plants.  Although etofenprox is described as an insecticide
and is therefore not anticipated to cause adverse effects to plants,
acceptable data are needed to confirm whether this is the case or not.

There are no reviewed environmental fate data for etofenprox.  These
data are needed to adequately characterize the environmental fate of
etofenprox associated with the use as an outdoor fogger.  Without
acceptable fate data for etofenprox, many conservative assumptions will
be used to estimate environmental concentrations.  Some important
assumptions are that etofenprox does not degrade or volatilize and that
for aquatic exposure estimates, 100% of the active ingredient reaches
the water body and stays in the water column.

Unlike agricultural pesticides, where estimated exposure concentrations
are based on label-specified application rates, fogger uses require an
alternate approach because there is no specified application rate.

To be conservative, we will estimate potential exposures based on the
use of one entire can of patio fogger at a single time.  This likely
represents the maximum reasonable use rate and would represent a
homeowner spraying a considerable amount of their patio and/or back
yard.

The yard and patio fogger label states that one can treats up to 10,000
square feet.  Hence, exposure estimates to terrestrial species will be
based on the amount of etofenprox in one 15 oz. can applied to 10,000
square feet.  This value will be converted to lbs a.i./acre.

For aquatic exposure estimates, we will assume that one 15 oz. can has
been discharged into the standard farm pond scenario.  We recognize that
this is an extremely unlikely event.  However, in the absence of
suitable fate data, this approach will likely generate an extremely
conservative estimate of possible exposure concentrations.

Refinements to the exposure estimates can be made when suitable
environmental fate data are available or when EFED is provided typical
use patterns for the outdoor fogger.  This pattern might include typical
spray durations or areas covered.

Preliminary Assessment: Based on Complete Discharge of Fogger

Assuming a specific gravity of 1 g/ml and 0.5% etofenprox applied over
10,000 square feet, the preliminary estimated application rate would be
about 0.021 lbs a.i./acre.  Using this as an application rate input into
T-REX (v.1.2.3) yielded estimated environmental concentrations (EECs)
for terrestrial species food items that ranged from 0.3 to 5.0 ppm; no
RQs exceeded any acute risk LOCs for birds and mammals.  No reviewed
chronic toxicity data are available for birds; however, the chronic risk
LOC was not exceeded for mammals based on endpoints identified by the
Health Effects Division.

Estimated exposure concentrations for aquatic species were calculated by
assuming one 15 oz. can is discharged into the standard farm pond water
body, which is 20,000 cubic meters.  One 15 oz. can contains
approximately 2.22 g etofenprox (assuming a specific gravity of 1 g/ml).
 Dividing 2.22g by 20,000 cubic meters and converting to ppb yields an
estimated exposure concentration of 0.10 µg/L (ppb). The acute RQs for
freshwater fish and invertebrates are 0.04 and 0.19, respectively.
These results indicate that the listed species acute risk LOC is
exceeded for aquatic invertebrates.

The estimated exposure concentration for aquatic species is very
conservative, assuming that users will not discharge the fogger directly
into water bodies.  Another interpretation of this approach is that a
user near a water body discharges an entire can in their back yard and
100% runoff of etofenprox occurs.  This too is highly unlikely.
Assuming further that any etofenprox that enters a water body is the
result of runoff or spray drift, at least 27% of the etofenprox sprayed
would have to enter the water body to result in RQs that exceed the
acute risk LOC for listed invertebrates.

Preliminary Assessment: Based on Spot Treatment for Pets

There is potential for discharge of etofenprox into surface water as a
result of washing pets (cats only) that have been treated with
etofenprox as a preventative spot treatment.  EECs are estimated using
multiple conservative assumptions and the USEPA OPPT Down-the-Drain
component of the E-FAST model.

It assumes that there is no degradation of etofenprox as a result of
water flows through treatment works and that 100% of the applied
etofenprox is washed off the cat and is dissolved in the waste water.

Given a spot treatment containing 55% etofenprox, a specific gravity of
1.062, and a treatment volume of 2 ml, the amount of etofenprox in one
treatment is about 1.17 g.  Based on the Down-the-Drain component of the
E-FAST model, the 50th percentile per capita daily indoor water usage is
388 L per person, or 1552 L per day for a family of four.  The
concentration of etofenprox in the waste stream given the above
conditions would be 753 ppb ((g/L).  However, this estimated
concentration would be diluted by the wastewater flows from other
households that do not have pets and/or are not using the etofenprox
formulated treatment and/or are not washing their pets on a given day.
The American Water Works Association estimates that total per capita
wastewater production for municipalities is about 689 L/person/day.  A
recalculation of the estimated etofenprox calculation using this water
usage estimate yields an EEC of 424 ppb.

In a typical 50,000 person municipality, the number of cats that must be
washed on a given day to equal the endangered species LOC for freshwater
invertebrates (0.57 µg/L X 0.05 = 0.0285 µg/L) and fish (2.7 µg/L X
0.05 = 0.135 µg/L) would be:

Aquatic Invertebrates:

	Number of cats = [(0.0285 g/L)(50,000 people)(689 L/person)]/1.2E+06
µg/dog)

		Number of cats = 0.84

Fish

	Number of cats = [(0.135 g/L)(50,000 people)(689 L/person)]/1.2E+06
µg/dog)

 		Number of cats = 3.98

This analysis indicates that in a municipality of 50,000 people, there
would be sufficient etofenprox in the untreated municipal wastewater
discharge from treatment facilities to exceed the listed species acute
risk LOC for invertebrates if one cat was washed.  For listed fish, four
cats would need to be washed for concentrations of etofenprox in the
untreated wastewater to exceed the listed species acute risk LOC.

As stated above, this approach incorporates several conservative
assumptions.  The assessment method assumes that 100% of the etofenprox
applied to cats is removed during pet washing.  This is a conservative
assumption considering that many spot treatments are designed to be
absorbed by the pet thereby providing extended protection.  Furthermore,
this assessment assumes that 100% of the etofenprox washed from a pet
remains in the water column.  Given that etofenprox is similar to
pyrethroids, it is possible that etofenprox will sorb to sediments or
other solids thereby reducing availability.  In addition, there is the
potential for microbial degradation within treatment facilities that
would further reduce etofenprox concentrations.  Environmental fate data
for etofenprox is needed to better address these assumptions and
uncertainties.

Conclusions Based on Preliminary Assessment Methods

Based on these preliminary exposure estimates, previous risk assessment
endpoints, and the assumptions discussed above, risks (due to direct
effects from acute exposure) are possible to listed aquatic
invertebrates.  The potential for direct adverse effects as a result of
chronic exposures were not estimated for taxa other than mammals because
chronic toxicity data are not reviewed.  Therefore, chronic risks to
listed birds (and, thus, reptiles, terrestrial amphibians), aquatic
invertebrates, and fish (and, thus, aquatic phase amphibians) cannot be
precluded at this time.  Similarly, toxicity data are not reviewed for
aquatic and terrestrial plants and hence, risks to species in these taxa
are presumed.

Because of the potential risk from direct effects to the listed and
non-listed taxa described above, should exposure occur, listed species
in all taxa may potentially be affected indirectly due to alterations in
food availability or habitat.

If the planned ecological risk assessment continues to indicate that
etofenprox may potentially impact, either directly or indirectly, listed
species and/or their designated critical habitat (if applicable), and
therefore does not support a “no effect” determination, further
refinements will be made.  This will involve determining whether use of
etofenprox “may affect” a particular listed species, and if so,
whether it is “likely to adversely affect” the species, or in the
case of designated critical habitat, whether use of the pesticide may
destroy or adversely modify any principle constituent elements for the
critical habitat, and if so, whether the expected impacts are “likely
to adversely affect” the critical habitat.  The first step in the
process is to improve the exposure estimates based on refining the
geographic proximity of etofenprox’s use and the listed species and/or
critical habitat.  If there is no geographic proximity, this information
would support a determination that etofenprox use will have no effect on
the species or critical habitat.  If after conducting the first step of
this analysis the Agency determines that geographic proximity exists,
both potential direct effects and any potential indirect effects of the
pesticide use will be examined.  This process is consistent with the
Agency's Overview Document.  The Agency will consult as necessary with
the U.S. Fish and Wildlife Service and National Marine Fisheries Service
(Services), consistent with the Services' regulations.

If the baseline risk assessment identifies potential concerns for
indirect effects on listed species, the next step for EPA and the
Services would be to identify which listed species and critical habitat
are potentially implicated.  Analytically, the identification of such
species and critical habitat can occur in either of two ways.  First,
the agencies could determine whether the action area overlaps critical
habitat or the occupied range of any listed species.  If so, EPA would
examine whether etofenprox’s potential impacts on non-endangered
species would affect the listed species indirectly or directly affect a
constituent element of the critical habitat.  Alternatively, the
agencies could determine which listed species depend on biological
resources, or have constituent elements that fall into, the taxa that
may be directly or indirectly impacted by etofenprox.  Then EPA would
determine whether the use of etofenprox overlaps the critical habitat or
the occupied range of those listed species.

ANTICIPATED DATA NEEDS

In order to more fully estimate and characterize the potential for
adverse environmental effects associated with the use of the etofenprox
outdoor fogger, the Agency needs a complete ecotoxicity and
environmental fate dataset.  Submission of these studies is likely to
have a significant impact on risk estimation and conclusions.  The
Agency is aware that ecotoxicity and environmental fate studies have
been submitted and review of these should commence during the Section 3
registration process initiated in 2007 for the proposed uses of
etofenprox on rice and/or as a mosquitocide.

The Agency will also conduct a search of the open literature to ensure
that all best available science is utilized.  The Agency uses the ECOTOX
database as its mechanism for searching the open literature for
ecological effects information.  ECOTOX integrates three previously
independent databases - AQUIRE, PHYTOTOX, and TERRETOX - into a system
which includes toxicity data derived predominately from the
peer-reviewed literature, for aquatic life, terrestrial plants, and
terrestrial wildlife, respectively.

OTHER INFORMATION NEEDS

There is specific information that will assist the Agency in refining
the ecological risk assessment, including any species-specific effects
determinations.  The Agency is interested in obtaining the following
information:

typical use patterns for the yard and patio fogger

typical sites of application

duration of spray events

any information regarding the potential for drift

maximum application rates

annual frequency of application, date of initial application per year,
application intervals, and maximum number of applications per year

any geographic limitations on use

state or local use restrictions

ecological incidents (non-target plant damage and avian, fish,
reptilian, amphibian and mammalian mortalities) not already reported to
the Agency

monitoring data

environmental fate and toxicity data on any etofenprox degradates of
concern that may be identified

The analysis plan will be revisited and may be revised depending upon
the data available in the open literature and the information submitted
by the public in response to the opening of the Registration Review
docket.

REFERENCES

USEPA.  2004.  Overview of the Ecological Risk Assessment Process in the
Office of Pesticide Programs, U.S. Environmental Protection Agency.
Endangered and Threatened Species Effects Determinations.  U.S.
Environmental Protection Agency, Office of Prevention, Pesticides and
Toxic Substances, Office of Pesticide Programs, Washington, DC.  January
23, 2004.

APPENDIX A:  Current Etofenprox Registrations and Uses

ETOFENPROX REGISTRATIONS:

EPA Reg. #	Name	Percent Active Ingredient

2724-667	CRAWLING INSECT KILLER I	1

2724-675	PREMIUM ROACH SPRAY	1

2724-677	YARD & PATIO FOGGER	0.5

2724-699	CRAWLING INSECT KILLER II	0.5

33657-34	YARD AND PATIO FOGGER	0.5

33657-36	CRAWLING INSECT KILLER I	1

33657-37	PREMIUM ROACH SPRAY	1

2724-668	FLYING INSECT KILLER II	0.5

2724-700	ETOFENPROX IGR FOGGER I	1

2724-701	ETOFENPROX IGR HOME AND CARPET SPRAY 1(2)	1

2724-702	ETOFENPROX IGR HOME & CARPET SPRAY II	0.5

33657-35	FLYING INSECT KILLER II	0.5

33657-7	ETOFENPROX 3 EMULSIFIABLE CONCENTRATE	32.5

33657-8	1% ETOFENPROX FOGGER	1

33657-9	1% ETOFENPROX AEROSOL	1

69332-3	SPI #8208-55D	55

69332-4	PL #1001 ETOFENPROX SPOT-ON	55

2724-504	RF2004 (CCSO)	40

2724-705	ETOFENPROX IGR FOGGER II	0.5

2724-786	RF2050 SPRAY	0.5

APPENDIX B:  Past Ecological Risk Assessments for Etofenprox

DOCUMENT DATE	TYPE OF REGISTRATION/

ASSESSMENT	USE(S)	POTENTIAL RISK IDENTIFIED	SUMMARIZED ECOLOGICAL
CONCLUSIONS

9/20/1999	S3NU	Indoor crack and crevice	No	No exposure

3/16/2006	S18	Rice in Louisiana	Yes	Potential to adversely affect
aquatic invertebrates and fish.  Potential for direct adverse effects to
2 listed fish species and potential for adverse indirect effects to
other listed species.  Inadequate data to characterize risk to listed
species.

1/31/2007	S18	Rice in Louisiana	Yes	Potential to adversely affect
aquatic invertebrates and fish.  Potential for direct adverse effects to
2 listed fish species and potential for adverse indirect effects to 2
listed bird species.  Inadequate data to characterize risk to listed
species.

APPENDIX C:  Preliminary EECs and RQs for Aquatic and Terrestrial
Organisms

Table 1. Agency Levels of Concern (LOCs).

Risk Presumption	Taxa	LOC

Acute Risk	Birds, mammals, aquatic animals	0.5

	Plants	1

Acute Restricted Use	Birds, mammals	0.2

	Aquatic animals	0.1

Acute Endangered Species	Birds, mammals	0.1

	Aquatic animals	0.05

	Plants	1

Chronic Risk	Birds, mammals, aquatic animals	1

Table 2.  Preliminary Tier I Aquatic Estimated Environmental
Concentrations (EEC) of Etofenprox, reported in µg/L.

Use pattern	EPA Reg. No.	Max. use amount	Peak EEC	Notes on Assessment
Method

Patio fogger

1- 15 oz. can	0.10 ppb	Based on discharge of one can into standard farm
pond.

Spot Treatment

1 – 2 ml applicator (per pet)	424-723 ppb	Estimate for one household;
see assessment text for more details.

Table 3.  Summary of Preliminary Risk Quotient Calculations for Aquatic
Organisms for Various Etofenprox Application Rates.

Use pattern	EPA Reg. No.	Max. use amount	RQ

	Aquatic Invertebrate	Fish	Non-Vascular Aquatic Plant

Patio fogger

1 – 15 oz. can	0.19	0.04	No Data

Spot Treatment

1 – 2 ml applicator (per pet)	See Assessment Text for Discussion

Table 4. Summary of Preliminary Risk Quotient Calculations for Mammals
Based on Upper Bound Kenega EECs (Calculated Using T-REX 1.3.1, and the
Estimated Application Rate Based on Fogger Use – 0.021 lb a.i./acre.

Table X. Upper 90th Percentile Kenaga, Acute Avian Dose-Based  Risk
Quotients

Size Class

(grams)	Adjusted

LD50	EECs and RQs

Short Grass	Tall Grass	Broadleaf Plants/

Small Insects	Fruits/Pods/

Seeds/

Large Insects

EEC	RQ	EEC	RQ	EEC	RQ	EEC	RQ

20	1440.86	5.74	0.00	2.63	0.00	3.23	0.00	0.36	0.00

100	1834.29	3.27	0.00	1.50	0.00	1.84	0.00	0.20	0.00

1000	2591.00	1.47	0.00	0.67	0.00	0.82	0.00	0.09	0.00

Table X.  Upper 90th Percentile Kenega, Subacute Avian Dietary Based
Risk Quotients

LC50	EECs and RQs

	Short Grass	Tall Grass	Broadleaf Plants/

Small Insects	Fruits/Pods/

Seeds/

Large Insects

	EEC	RQ	EEC	RQ	EEC	RQ	EEC	RQ

5000	5.04	0.00	2.31	0.00	2.84	0.00	0.32	0.00

Size class not used for dietary risk quotients

Table X.  Upper 90th Percentile Kenega, Chronic Avian Dietary Based Risk
Quotients

NOAEC (ppm)	EECs and RQs

	Short Grass	Tall Grass	Broadleaf Plants/

Small Insects	Fruits/Pods/

Seeds/

Large Insects

	EEC	RQ	EEC	RQ	EEC	RQ	EEC	RQ

0	5.04	#####	2.31	#####	2.84	#####	0.32	#####

Size class not used for dietary risk quotients

Table X. Upper 90th Percentile Kenaga, Acute  Mammalian Dose-Based  Risk
Quotients

Size Class

(grams)	Adjusted

LD50	EECs and RQs

Short Grass	Tall Grass	Broadleaf Plants/

Small Insects	Fruits/Pods/

Seeds/

Large Insects	Granivore

EEC	RQ	EEC	RQ	EEC	RQ	EEC	RQ	EEC	RQ

15	10989.15	4.81	0.00	2.20	0.00	2.70	0.00	0.30	0.00	0.07	0.00

35	8891.40	3.32	0.00	1.52	0.00	1.87	0.00	0.21	0.00	0.05	0.00

1000	3845.80	0.77	0.00	0.35	0.00	0.43	0.00	0.05	0.00	0.01	0.00

Table X.  Upper 90th Percentile Kenega, Acute Mammalian Dietary Based
Risk Quotients

LC50 (ppm)	EECs and RQs

	Short Grass	Tall Grass	Broadleaf Plants/

Small Insects	Fruits/Pods/

Seeds/

Large Insects

	EEC	RQ	EEC	RQ	EEC	RQ	EEC	RQ

0	5.04	#####	2.31	#####	2.84	#####	0.32	#####

Size class not used for dietary risk quotients

Table X.  Upper 90th Percentile Kenega, Chronic Mammalian Dietary Based
Risk Quotients

NOAEC (ppm)	EECs and RQs

	Short Grass	Tall Grass	Broadleaf Plants/

Small Insects	Fruits/Pods/

Seeds/

Large Insects

	EEC	RQ	EEC	RQ	EEC	RQ	EEC	RQ

74	5.04	0.07	2.31	0.03	2.84	0.04	0.32	0.00

Size class not used for dietary risk quotients

Table X.  Upper 90th Percentile Kenega, Chronic Mammalian Dose-Based
Risk Quotients

Size Class

(grams)	Adjusted NOAEL	EECs and RQs

Short Grass	Tall Grass	Broadleaf Plants/

Small Insects	Fruits/Pods/

Seeds/

Large Insects	Granivore

EEC	RQ	EEC	RQ	EEC	RQ	EEC	RQ	EEC	RQ

15	8.13	4.81	0.59	2.20	0.27	2.70	0.33	0.30	0.04	0.07	0.01

35	6.58	3.32	0.50	1.52	0.23	1.87	0.28	0.21	0.03	0.05	0.01

1000	2.85	0.77	0.27	0.35	0.12	0.43	0.15	0.05	0.02	0.01	0.00

IV. HUMAN HEALTH EFFECTS SCOPING DOCUMENT

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF

PREVENTION, PESTICIDES AND

TOXIC SUBSTANCES

May 16, 2007

  SEQ CHAPTER \h \r 1 MEMORANDUM

SUBJECT:	Etofenprox/Ethofenprox:  HED Registration Review Problem
Formulation Document.

		PC Code: 128965 ; DP Barcode: D337767.

FROM:	Donna Davis, Chemist & Risk Assessor

		Timothy Dole, CIH, Industrial Hygienist

		Whang Phang, Toxicologist

		Reregistration Branch 1

		Heath Effects Division (7509P)

THROUGH:	Deborah Smegal, MPH, Senior Scientist

		Michael S. Metzger, Branch Chief

		Reregistration Branch 1

		Health Effects Division (7509P)

TO:		Dayton Eckerson, Chemical Review Manager

Special Review and Reregistration Division (7508P)

Attached please find the Health Effects Division’s Chapter of the
Etofenprox (also known as Ethofenprox) Problem Formulation Document to
support the Registration Review of this chemical.

Section 1.  Introduction

The HED Etofenprox Registration Review Team evaluated the available data
and the most recent human health risk assessments for the insecticide,
etofenprox (also known as ethofenprox), to determine the scope of work
necessary to support the registration review process.  The team
considered the current use patterns as well as the available toxicity
and exposure information for etofenprox.  The primary source for the
status update was the most recent HED Human Health Risk Assessment
conducted in April of 2006 (D327831, J. Arthur, 4/5/2006).  A
comprehensive listing of all sources consulted during problem
formulation is presented in Section 12 of this document.

The purpose of this screen is to determine whether sufficient data are
available to assess the safety of this pesticide, as well as to
determine whether any new data have been submitted since the last
assessment that would necessitate conducting a new human health risk
assessment to support Registration Review.  The HED Etofenprox
Registration Review team includes Donna Davis (chemistry/risk
assessment), Timothy Dole (occupational and residential exposure) and
Whang Phang (toxicology).

Etofenprox is an insecticide that is currently registered for use as a
spot treatment to cats, in indoor and outdoor residential settings, as
well as for use in other public and private settings, including the
nonfood-handling areas of commercial food-handling establishments.  HED
is not aware of any agricultural use registrations for etofenprox and
there are no tolerances established for etofenprox.

Section 2.  Physical/Chemical Properties

Physical and Chemical properties for etofenprox are summarized in Table
1, below.

Table 1.  Physical/Chemical Properties of Etofenprox

Structure

Common Name	Etofenprox; also known as Ethofenprox

Chemical Name	2-[ethoxyphenyl]-2-methylpropyl-3-phenoxy benzyl ether

CAS Number	080844-07-1

Chemical Formula	C25H28O3

Physical State	White crystalline powder

Molecular Weight	376.47

Melting Point1 	36.4 – 38.0 °C

Boiling Point			200 °C at 0.18 mm Hg

Water Solubility1		 	0.0225 mg/L at 20 °C

Vapor Pressure1	2.5 x 10-8  mm Hg at 25 °C

Octanol-water Partition Coefficient (KOW)1	7.94 x 106

Specific Gravity	solid (23 °C): 	1.157 g/ml

liquid (40.1 °C): 	1.067 g/ml

Solubility

(g ai/100 ml solvent)

	acetone		 780 at 25°C

n-hexane	 270 at 25°C

methanol	 6.6 at 25°C

xylene		 480 at 25°C

Stability to heat			No loss during at least 3 months storage at 80°C.
Partial degradation at 100°C

Hydrolysis:			Stable in aqueous 1N NaOH or 1N HCL for at least 10 days.

1 Unreviewed data submitted to EFED and cited as Tognucci 2000 in EFED
memorandum D335102, G. Orrick, 	1/31/2007.

Section 3.  Toxicology

Hazard Characterization

Etofenprox is a synthetic pyrethroid-like substance.  It differs in
structure from pyrethroids in that it lacks a carbonyl group.
Etofenprox contains an ether moiety whereas pyrethroids contain ester
moieties. Its mode of action against insects is very similar to that of
pyrethroids, and its main action site is the neuronal axon; however, its
toxicity in test animals is different from that of a pyrethroid.

Etofenprox has low acute toxicity via the oral, dermal, and inhalation
routes.  It is not an acute eye or skin irritant and is not a dermal
sensitizer.  However, with repeated dermal exposure, etofenprox causes
skin irritation.  The major target organs for etofenprox are the
thyroid, liver, and kidney.  Males appear to be more susceptible than
females. Etofenprox accumulates in fat, tissues or organs which contain
high fat composition, and milk.

Etofenprox produced treatment-related increases in the incidence of
thyroid follicular cell tumors at 187 mg/kg/day for males and at 249
mg/kg/day for females.  The Cancer Assessment Review Committee evaluated
the tumor incidence information and all related data and concluded that
there were sufficient data to demonstrate that perturbation of thyroid
homeostasis was the key event in the thyroid tumor formation after
exposure to etofenprox.  The Committee classified etofenprox as "Not
likely to be carcinogenic to humans at doses that do not alter thyroid
homeostasis”.

The most recent review of the toxicology database for etofenprox
concluded that the database was complete and sufficient for selecting
toxicity endpoints for risk assessment.  HED is not aware of any new
toxicity data that have been submitted or are expected to be submitted
that will need to be reviewed during Registration Review.

The toxicity endpoints shown in Table 2, below were selected for the
latest risk assessment which was conducted in April, 2006.

Table 2.  Summary of Toxicological Doses and Endpoints for Etofenprox
for Use in Human Risk Assessments

Exposure

Scenario	Point of Departure	Uncertainty

Factor	RfD, Level of Concern for RA	Study and Toxicological Effects

Acute Dietary

(females 13-49) and General population	No adverse effects attributable
to a single dose of etofenprox were found in the database.

Chronic Dietary

(all populations)	NOAEL = 3.7 mg/kg/day	UFA  = 10x

UFH = 10x	RfD  = 0.037

mg/kg/day	Combined chronic toxicity/ carcinogenicity study in rats.

LOAEL=25.5 mg/kg/day based on increased thyroid weights. Related to
increased liver weights and histopathological changes in liver and
thyroid that occurred at the higher dose.

Incidental Oral

Short-Term

(1-30 days)	NOAEL=100 mg/kg/day	UFA  = 10x

UFH = 10x	LOC for MOE = 100	Developmental Toxicity in rabbit LOAEL = 300
mg/kg/day based on  decreased body weights, body weight gains, and food
consumption (maternal effects)

Incidental Oral

Intermediate- Term

(1- 6 months) 	NOAEL =20 mg/kg/day	UFA  = 10x

UFH = 10x	LOC for MOE = 100	Subchronic oral toxicity in rats LOAEL = 120
mg/kg/day based on decreased body weight gain, increased liver and
thyroid weights with corresponding histopathology, changes in
hematology, and clinical chemistry.

Dermal

(all durations)	Not required.  No systemic toxicity was found in the
dermal 28-day study at the highest dose tested (1000 mg/kg/day); no
developmental, or other toxicity not measured in dermal studies was
observed in the database.

Inhalation

(All durations)

	NOAEL = 10.6 mg/kg/day	UFA  = 10x

UFH = 10x	LOC for MOE  = 100

(Residential  and Occupational)	13- week inhalation toxicity study in
rats.  LOAEL=52.3 mg/kg/day based on organ weight changes and
histopathological changes in liver, adrenal, and thyroid.

Cancer Classification	“Not Likely to be carcinogenic to humans at
doses that do not alter rat thyroid hormone homeostasis.”

NOAEL = no observed adverse effect level.  LOAEL = lowest observed
adverse effect level.  UF = uncertainty factor.  UFA = extrapolation
from animal to human (interspecies). UFH = potential variation in
sensitivity among members of human population (intraspecies).  RfD =
reference dose.  MOE = margin of exposure.  LOC = level of concern.  RA
= risk assessment

The endpoints contained in Table 2 were reexamined by the Etofenprox
Registration Review Team.  The team noted that thyroid effects were seen
in several studies which were characterized by increases in thyroid
weights, changes in T4 and TSH levels, and an increase in the incidence
of thyroid follicular cell adenomas. The thyroid effects seen in the
studies with adult animals are of concern for the young animals because
changes in thyroid function in the developing animals may influence the
behavioral and nervous system developments.  However, the Etofenprox
Registration Review Team did not find that a comparative thyroid assay
was likely to be required since a developmental neurotoxicity study in
rats is available and shows that etofenprox produces alteration for
auditory startle and pup behavior at 169 mg/kg/day with a clear study
NOAEL for these behavioral and nervous system effects at 57 mg/kg/day.
This dose level is higher than the doses selected for most of the risk
assessments.  However, HED notes that the short-term incidental oral
endpoint is from a developmental toxicity study in the rabbit with a
NOAEL of 100 mg/kg/day.  The team recommends that the short-term oral
endpoint be reevaluated as part of Registration Review to determine if a
more appropriate point of departure, which would be protective of
thyroid effects in the young, should be selected from the developmental
neurotoxicity study.

With the exception of the short-term incidental oral endpoint, HED finds
that the endpoints contained in Table 2 appear to be consistent with
current science policy as well as valid based on the currently available
toxicity data, exposure durations, and use patterns.

HED does not anticipate that any new toxicology data would be required
for the registration review process.

Section 4.  Residue Chemistry

There are no permanently registered agricultural uses for this pesticide
at this time.  Etofenprox is currently registered for use in indoor and
outdoor residential settings, as well as for use in other public and
private settings, including the nonfood-handling areas of commercial
food-handling establishments.  No residue data have been submitted to
support the proposed uses in commercial establishments or residential
settings.  HED has previously recommended that the labels for these uses
include the following restrictions:

The label should indicate that food must be removed (not merely covered)
from food serving areas of commercial establishments prior to treatment,
and food-serving surfaces must be washed prior to returning food.

In homes, remove all food and cooking utensils, and cover all food
handling surfaces and wash thoroughly after treatment and before use.

With the recommended restrictions, it is unlikely that significant
contamination of foods in commercial or residential settings will occur;
therefore food residue data to support the proposed commercial and
residential uses of etofenprox are not required.

No new residue chemistry data are required for the registration review
of etofenprox.

Section 5.  Residential Exposures and Risks

Residential handler exposures were assessed for aerosol can application.
 Only inhalation exposure was assessed since a dermal endpoint was not
selected.  All of the handler inhalation MOEs are above the target MOE
of 100; therefore, the handler risks are not of concern.

In the most recent risk assessment, residential post application
inhalation exposures were assessed for space sprays and yard and patio
foggers.  All of the post application inhalation MOEs are greater than
the target MOE of 100 and are not of concern.  Additionally, residential
post application incidental oral exposures were assessed for indoor
fogger deposition onto floor surfaces and yard and patio fogger
deposition onto turf. The incidental oral MOEs for these two scenarios
were greater than 100 and were not of concern.   The calculated
short-term incidental oral risks were based on the point of departure of
100 mg/kg/day from the developmental toxicity study in rabbits.  HED has
recommended that this point of departure be reevaluated.  Should that
reevaluation result in the use of a point of departure of 57 mg/kg/day
from the developmental neurotoxicity study, it appears that risks will
still not be of concern for these two scenarios.

Additionally, in the most recent risk assessment, post application
incidental oral exposures were assessed for toddler hand to mouth
contact with pet cats treated with etofenprox spot on products.   The
Etofenprox Registration Review Team evaluated the exposure assessment
for toddlers in contact with treated pets and concluded that some of the
original default assumptions in terms of surface area and weight of
animal should be revised. Further, as noted above, the incidental oral
endpoint may need to be revised.  A preliminary assessment addressing
revised default assumptions and a new endpoint indicates that risks may
still be above 100; however, the Etofenprox team recommends that this
scenario be fully reassessed as part of the Registration Review of
etofenprox.

Combined handler and post application inhalation exposures to adults
resulted in MOEs greater than 100 which are not of concern.  Combined
post application inhalation and incidental oral risks for toddlers
exposed to etofenprox either from contact with treated pets or from
contact with surface residues from indoor or outdoor uses should be
reevaluated as part of the Registration Review for etofenprox.

No additional exposure information is needed for the registration review
of etofenprox.

Section 6.  Drinking Water Exposure and Risk

  SEQ CHAPTER \h \r 1

EFED has determined that residues of etofenprox in water are likely to
be negligible based on the current use patterns; therefore, a drinking
water assessment is not required to support Registration Review.

Section 7.  Occupational Exposure and Risk

Dermal exposures were not assessed for either handler or post
application exposures because no systemic effects were observed at the
limit dose in dermal toxicity studies in animals.    SEQ CHAPTER \h \r 1
Based on toxicological criteria and potential for exposure, only
inhalation exposures were assessed for a variety of occupational handler
scenarios.

The occupational handler exposure scenarios that were assessed include
general indoor applications using low pressure hand wands and aerosol
spray cans.   All of the inhalation MOEs are above the target MOE of 100
and the risks are not of concern.

Occupational post application inhalation exposures were not assessed
because ethofenprox has a low vapor pressure and it is not applied in a
manner (such as thermal or cold fogging) that would generate significant
post application aerosol exposures.  Only one product appears to be
intended for commercial use (Etofenprox Emulsifiable Concentrate,
33657-7) and this product is applied only as a thin stream baseboard
spray.  The remaining products appear to be intended for consumer use.

No new data to address occupational exposures and risks are required to
support registration review of etofenprox.

Section 8.  Incident Reports

HED has reviewed the most currently available incident data for
etofenprox, including Poison Control Center Data (PCC), Incident Data
system Data (IDS) for 1999 through the present, and National Institute
of Occupational Safety and Health Sentinel Event Notification System for
Occupational Risks Data (NIOSH/SENSOR) for 1998 through 2003.

PCC data reviewed reflect incidents for 1993 through 2005.  No cases
were reported in the PCC database for Etofenprox during that time
period.

The IDS contains data starting in 1992 and continuing through the
present.  Five cases were reported in the IDS during this time period,
three cases in 2005 and two cases in 2006.  Symptoms were primarily skin
irritations with one case of muscle weakness and nausea reported.
Reports submitted to the IDS represent anecdotal reports or allegations
only.  Typically, OPP does not draw conclusions implicating the
pesticide as a cause of any of the reported health effects.

NIOSH/SENSOR data reviewed were from 1998 through 2006.  Out of 5,899
reported cases from 1998 to 2003, no case was reported in the
NIOSH/SENSOR database involving Etofenprox.

Section 9.  Anticipated Data Needs

HED does not anticipate that additional toxicology, residue chemistry or
occupational/residential exposure data will be required for the
etofenprox registration review process.

Section 10.  Tolerances

There are currently no food uses for etofenprox; therefore a discussion
of tolerances and international harmonization is not pertinent to this
registration review action.

Section 11.  Overall Conclusions

No new data will be required for the Registration Review of etofenprox.
 The short-term incidental oral endpoint and those risk assessments for
both individual and aggregate scenarios using that endpoint should be
reassessed during Registration Review.

Section 12.  Reference Memoranda

Etofenprox:  Revised HED Risk Assessment for Conditionally Registered
Residential Uses; D327831; J. Arthur; 4/6/2006

Etofenprox:  Occupational and Residential Exposure Assessment for
Proposed Section 3 Registration on Domestic Pets; D327844; J. Arthur;
4/6/2006

Etofenprox: Third Report of the Cancer Assessment Review Committee. PC
Code: 128965.  TXR No. 0054080. J. Kidwell; Feb. 8, 2006

Review of Ethofenprox Incident Reports; D337771; M. Hawkins; 4/20/2007

Etofenprox:  Transmittal of Section 18 for Granular Etofenprox to
Control rice Water Weevil in Louisiana, D335102, G. Orrick, 1/31/2007.

V.  GLOSSARY OF TERMS AND ABBREVIATIONS

ai			Active Ingredient

AR			Anticipated Residue

CFR			Code of Federal Regulations

cPAD			Chronic Population Adjusted Dose

CSF			Confidential Statement of Formula

CSFII			USDA Continuing Surveys for Food Intake by Individuals

DCI			Data Call-In

DEEM			Dietary Exposure Evaluation Model

DFR			Dislodgeable Foliar Residue

DNT			Developmental Neurotoxicity

DWLOC		Drinking Water Level of Comparison

EC			Emusifiable Concentrate Formulation

EDWC			Estimated Drinking Water Concentration

EEC			Estimated Environmental Concentration

EPA			Environmental Protection Agency

EUP			End-Use Product

FDA			Food and Drug Administration

FIFRA			Federal Insecticide, Fungicide, and Rodenticide Act

FFDCA		Federal Food, Drug, and Cosmetic Act

FQPA			Food Quality Protection Act

FOB			Functional Observation Battery

GENEEC		Tier I Surface Water Computer Model

IR			Index Reservoir

LC50	Median Lethal Concentration.  A statistically derived concentration
of a substance that can be expected to cause death in 50% of test
animals.  It is usually expressed as the weight of substance per weight
or volume of water, air or feed, e.g., mg/l, mg/kg or ppm.

LD50	Median Lethal Dose.  A statistically derived single dose that can
be expected to cause death in 50% of the test animals when administered
by the route indicated (oral, dermal, inhalation).  It is expressed as a
weight of substance per unit weight of animal, e.g., mg/kg.

LOC	Level of Concern

LOAEL	Lowest Observed Adverse Effect Level

µg/g	Micrograms Per Gram

µg/L	Microgram Per Liter

mg/kg/day	Milligram Per Kilogram Per Day

mg/L	Milligrams Per Liter

MOE	Margin of Exposure

MRID	Master Record Identification (number).  EPA’s system of recording
and tracking submitted studies.

MUP	Manufacturing-Use Product

NA	Not Applicable

NAWQA	USGS National Ambient Water Quality Assessment

NPDES	National Pollutant Discharge Elimination System

NR	Not Required

NOAEL	No Observed Adverse Effect Level

OPP	EPA Office of Pesticide Programs

OPPTS	EPA Office of Prevention, Pesticides and Toxic Substances

PAD	Population Adjusted Dose

PCA	Percent Crop Area

PDP	USDA Pesticide Data Program

PHED	Pesticide Handler’s Exposure Data

PHI	Preharvest Interval

ppb	Parts Per Billion

PPE	Personal Protective Equipment

ppm	Parts Per Million

PRZM/EXAMS	Tier II Surface Water Computer Model

Q1*	The Carcinogenic Potential of a Compound, Quantified by the EPA’s
Cancer Risk Model

RAC	Raw Agricultural Commodity

RED	Reregistration Eligibility Document

REI	Restricted Entry Interval

Rfd	Reference Dose

RQ	Risk Quotient

SCI-GROW	Tier I Ground Water Computer Model

SAP	Science Advisory Panel

SF	Safety Factor

SLN	Special Local Need (Registrations Under Section 24c) of FIFRA

TGAI	Technical Grade Active Ingredient

TRED 	Tolerance Reassessment and Risk Management Decision

USDA	United States Department of Agriculture

UF	Uncertainty Factor

WPS	Worker Protection Standard

Docket Number:  EPA-HQ-OPP-2007-0804

  HYPERLINK "http://www.regulations.gov"  www.regulations.gov

 PAGE

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Docket Number:  EPA-HQ-OPP-2007-0804

  HYPERLINK "http://www.regulations.gov"  www.regulations.gov

Uptake/ Adsorption

Aquatic Plants

Plant Population

Reduced population growth

Individual Vertebrates and Invertebrates Reduced survival or
reproduction

Individual Plants

Reduced survival, growth, or reproduction

Wetland/ Riparian

Plants

Aquatic Invertebrates,

Vertebrates

Attribute

Changes

Receptors

Gill/

 Integument Uptake

Direct Contact/

Root Uptake

Exposure

Route

Receiving Water Body/ Sediment

Riparian/

Wetland Foliage/Soil

Source/

Exposure

Media

Wastewater flow

Source/

Transport

Pathways

Washing Pet After Etofenprox Used as Spot Treatment

Stressor

Spray

Drift

Uptake/ Adsorption

Aquatic Plants

Plant Population

Reduced population growth

Individual Vertebrates and Invertebrates Reduced survival or
reproduction

Individual Plants

Reduced survival, growth, or reproduction

Wetland/ Riparian

Plants

Aquatic Invertebrates,

Vertebrates

Individual Animals

Reduced survival or reproduction

Terrestrial

Upland

Plants

Terrestrial Vertebrates:

Birds, Mammals,

Reptiles, Terrestrial Phase Amphibians

Attribute

Changes

Receptors

Gill/

 Integument Uptake

Direct Contact/

Root Uptake

Direct Contact/

Root Uptake

Ingestion

Exposure

Route

Ground Water

Receiving Water Body/ Sediment

Riparian/

Wetland Foliage/Soil

Upland

Foliage/Soil

Terrestrial Food Items (foliage, fruit, insects, seeds)

Source/

Exposure

Media

Leaching

(Infiltration/

Percolation

Direct Application

Source/

Transport

Pathways

Etofenprox Applied as Yard and Patio Fogger

Stressor