Document ID: EPA-HQ-OPP-2010-0022-0012
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2010-03-31T04:00Z

Docket Number:  EPA-HQ-OPP-2010-0022

www.regulations.gov

The Allethrins Summary Document

Registration Review: Initial Docket

	March 2010	

 

TABLE OF CONTENTS

										    Page #

Preliminary Work Plan (PWP)					  4

Fact Sheet								  11

________________________________________

Please Note

This Preliminary Work Plan and Fact Sheet summarize the Environmental
Protection Agency's current position based on the following documents:

Registration Review: Preliminary Problem Formulation for Environmental
Fate, 

Ecological Risk, and Endangered Species Assessments for the Allethrins. 
March 9, 2009.

Allethrins.  Human Health Assessment Scoping Document in Support of
Registration Review.  March 5, 2010.

Revised Reregistration Eligibility Decision for the Allethrins.  May 27,
2009.  (Available from
http://www.epa.gov/oppsrrd1/REDs/allethrins-amended-red.pdf)

Updated Review of The Allethrins Incident Reports.  August 29, 2009.

Screening Level Use Analysis (SLUA) for Allethrins.  June 5, 2009.

Appendix A for Allethrins.  May 29, 2009.

Additional supporting documents for the allethrins may be found in the
docket located on the internet at   HYPERLINK
"http://www.regulations.gov"  www.regulations.gov .

I.  Preliminary Work Plan – The Allethrins

Introduction:

The Food Quality Protection Act (FQPA) of 1996 mandated a registration
review program.  All pesticides sold or distributed in the United States
generally must be registered by the Environmental Protection Agency
(EPA), based on scientific data showing that they will not cause
unreasonable risks to human health or the environment when used as
directed on product labeling.  The registration review program is
intended to make sure that, as the ability to assess risk evolves and as
policies and practices change, all registered pesticides continue to
meet the statutory standard of no unreasonable adverse effects to human
health or the environment.  Changes in science, public policy, and
pesticide use practices will occur over time.  Through the registration
review program, the Agency periodically reevaluates pesticides to make
sure that as change occurs, products in the marketplace can be used
safely.  Information on this program is provided at:
http://www.epa.gov/oppsrrd1/registration_review/. 

The Agency is implementing the registration review program pursuant to
Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act
(FIFRA), and will review each registered pesticide every 15 years to
determine whether it continues to meet the FIFRA standard for
registration.  The Agency will consider benefits information and data as
required by FIFRA.  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 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 the registration review of the allethrins.

The allethrins are members of the pyrethroid class of insecticides. The
allethrin series includes bioallethrin, esbiol, esbiothrin, and pynamin
forte.  They are used to control flying and crawling insects in a number
of commercial, horticultural and residential applications.  Common
product forms include wasp and hornet aerosols; yard and patio foggers;
flying insect killer aerosols; total release aerosols (indoor foggers);
mosquito repellants (mats and coils); space sprays; and crawling insect
killer aerosols.  The allethrins are registered for both indoor and
outdoor uses.  Outdoor product are applied to localized treatment areas
and are limited to foggers and spot treatments that are typically
packaged as small, hand-held units and mosquito repellent mats and
coils.  There are no food uses for allethrins; all food uses were
cancelled in 2004 (69 FR 188). 

The allethrins were the subjects of a Reregistration Eligibility
Decision (RED), which was completed on June 30, 2007.  Subsequent to
publication of the RED, the technical registrant (Valent BioSciences
Corporation) identified a product (EPA registration number 21165-62)
registered for use in commercial animal housing automatic misting
systems.  This use was not addressed in the 2007 RED or in the
supporting risk assessments.  As a result, the Agency updated the
allethrins occupational and residential risk assessment to include an
evaluation of this product and use pattern, and revised the RED
accordingly.  All other risk assessments described in the original RED
remained the same.  The RED Amendment was finalized on May 27, 2009.  

Anticipated Risk Assessment and Data Needs:

The Agency intends to require data needed to update and revise the
ecological risk assessment for the allethrins (including an endangered
species risk assessment) and update and revise the human health risk
assessment.  Below is a summary of the issues relevant to the
registration review of the allethrins and the data the Agency plans to
require:

Ecological Risk:

The most recent ecological risk assessment was completed to support the
allethrins RED in April 2007. 

The Agency has not conducted a risk assessment that supports a complete
endangered species determination.  The ecological risk assessment
planned during registration review will allow the Agency to determine
whether use of the allethrins has “no effect” or “may affect”
federally listed threatened or endangered species (listed species) or
their designated critical habitats.  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/or National Marine Fisheries Services (the
Services), as appropriate.

An updated ecological assessment is planned to be conducted to
incorporate new data and any relevant changes to risk assessment
methodologies.

The Agency intends to require the following data in order to conduct a
complete ecological risk assessment, including an endangered species
assessment, for all uses:

Guideline number (GLN) 850.4100 – Seedling Emergence Phytoxicity (Tier
II)  

GLN 850.4150 – Vegetative Vigor Phytoxicity (Tier II)1

GLN 850.3030 – Honey Bee Toxicity of Residues on Foliage

Please refer to the Registration Review: Preliminary Problem Formulation
for Environmental Fate, Ecological Risk, and Endangered Species
Assessments for the Allethrins located in the docket, for a detailed
discussion of the anticipated risk assessment needs.

Human Health Risk:

The most recent comprehensive human health assessment was completed on
June 27, 2007 in support of reregistration and a petition to establish a
tolerance for use in food handling establishments (FHE).

The Agency does not plan to conduct a drinking water assessment for the
allethrins, since registered outdoor use is limited to spot treatment
only.  

During registration review, the Agency foresees conducting a full
reassessment of dietary (food only), occupational, residential, and
aggregate risk, taking into account anticipated changes to toxicological
endpoints, safety factors, exposure values, and applicable standard
operating procedures.

An immunotoxicity study (GLN 870.7800), an inhalation indoor exposure
study (875.1400), a UV/Visible absorption study (870.7800), and a
developmental neurotoxicity (DNT) study (GLN 870.6300) were required in
the allethrins reregistration generic data call-in (GDCI) issued in
December 2009.  The immunotoxicity and inhalation exposure data is due
in June 2011, the UV/Visible absorption data is due in August 2010, and
the DNT data is due in December 2013.

Based on the Agency’s review of existing pyrethroid data, EPA has come
to the conclusion that the DNT is not a particularly sensitive study for
comparing the sensitivity of young and adult animals to pyrethroids. 
EPA has recently determined that, as an alternative to the generation
and submission of a new DNT study, pyrethroid registrants may instead
choose to cite the six previously submitted DNT studies for pyrethroid
pesticides.  The Agency is also investigating the need for additional
experimentation, specific to the mode of action and pharmacokinetic
characteristics of pyrethroids, to evaluate the potential for increased
susceptibility of young organisms.  A meeting of the FIFRA Scientific
Advisor Panel (SAP) is planned for July 2010 to discuss this issue.  EPA
is currently soliciting proposals for study design and protocols to
evaluate potential differential sensitivity between juvenile and adult
rats.  For more information on the pyrethroid DNT requirement, see  
HYPERLINK
"http://www.epa.gov/oppsrrd1/reevaluation/pyrethroids-pyrethrins.html" 
http://www.epa.gov/oppsrrd1/reevaluation/pyrethroids-pyrethrins.html .

During the registration review human health scoping process for the
allethrins, several additional uncertainties in the toxicity data base
were identified.  

Dosing in the submitted mouse carcinogenicity study (MRID 41519804) with
esbiothrin was considered inadequate and was not supported by the 8-week
range-finding study.  Therefore, a 90-day oral toxicity study in rodents
(GLN 870.3100) for esbiothrin is required to determine if doses in the
submitted mouse carcinogenicity study (GLN 870.4200) were adequate.  If
not, then a new mouse carcinogenicity study must be conducted.  

A micronucleus assay with esbiothrin was previously submitted and
classified as unacceptable.  This data is still required.  The new 40
CFR part 158 guideline in vivo cytogenetics study (GLN 870.5395) will be
required to fill this mutagenicity data gap.  

The Agency will likely require the following data in the registration
review DCI for the allethrins in order to conduct a complete human
health assessment:

GLN 870.5395 – In Vivo Cytogenetics  

GLN 870.3100 – 90-day Oral Toxicity in Rodents

GLN 870.4200 – Carcinogenicity Study in Mice 

The Agency will make a decision regarding the need for an FQPA or other
database uncertainty/safety factors for the allethrins following receipt
of required toxicity data and following a final determination of the
potential for increased susceptibility of infants and children to
pyrethroid pesticides based on the results of all available data.  

The allethrins are members of the pyrethroid class of insecticides. 
This class also includes permethrin, cypermethrin, cyfluthrin,
tau-fluvalinate, bifenthrin, fenpropathrin, and lambda-cyhalothrin,
among others.  EPA developed a draft science policy document on the
proposed common mechanism of toxicity for naturally-occurring pyrethrins
and synthetic pyrethroids (Proposed common mechanism grouping for the
pyrethrins and pyrethroids, draft, May 19, 2009;   HYPERLINK
"http://www.regulations.gov/search/Regs/home.html#documentDetail?R=09000
064809a62df" 
http://www.regulations.gov/search/Regs/home.html#documentDetail?R=090000
64809a62df  ).  This document was supported by the FIFRA Scientific
Advisory Panel (SAP) and is available in the docket (  HYPERLINK
"http://www.regulations.gov/search/Regs/home.html#documentDetail?R=09000
06480a1f8d7" 
http://www.regulations.gov/search/Regs/home.html#documentDetail?R=090000
6480a1f8d7 ).  EPA will finalize the policy document on the pyrethroid
common mechanism of toxicity taking into account the SAP comments. 
Pesticides with a common mechanism of toxicity are subject to cumulative
risk assessment under the FQPA.  Research is on-going by EPA’s Office
of Research and Development (ORD) to make improvements to the Stochastic
Human Exposure and Dose Simulation (SHEDS) probabilistic exposure model,
which are important for the cumulative risk assessment.  EPA ORD is also
developing physiologically-based pharmacokinetic models for several
pyrethroids.  The status of both of these research modeling efforts will
be reviewed by the FIFRA SAP in July, 2010.  For information regarding
EPA’s efforts to evaluate the risk to pyrethroids, see   HYPERLINK
"http://www.epa.gov/oppsrrd1/reevaluation/pyrethroids-pyrethrins.html." 
http://www.epa.gov/oppsrrd1/reevaluation/pyrethroids-pyrethrins.html. 

Please refer to Human Health Scoping Document in Support of Registration
Review for the Allethrins, located in the docket, for a detailed
discussion of the anticipated risk assessment needs for human health.

Endocrine Disruptor Screening Program

As required under FFDCA section 408(p), EPA has developed the Endocrine
Disruptor Screening Program (EDSP) to determine whether certain
substances (including pesticide active and other ingredients) may have
an effect in humans or wildlife similar to an effect produced by a
“naturally occurring estrogen, or other such endocrine effects as the
Administrator may designate.”  The EDSP employs a two-tiered approach
to making the statutorily required determinations.  Tier 1 consists of a
battery of 11 screening assays to identify the potential of a chemical
substance to interact with the estrogen, androgen, or thyroid (E, A, or
T) hormonal systems.  Chemicals that go through Tier 1 screening and are
found to have the potential to interact with E, A, or T hormonal systems
will proceed to the next stage of the EDSP where EPA will determine
which, if any, of the Tier 2 tests are necessary based on the available
data.  Tier 2 testing is designed to identify any adverse endocrine
related effects caused by the substance, and establish a quantitative
relationship between the dose and the E, A, or T effect.

Between October 2009 and February 2010, EPA issued test orders/data
call-ins for the first group of 67 chemicals, which contains 58
pesticide active ingredients (ais) and 9 inert ingredients.  This list
of chemicals was selected based on the potential for human exposure
through pathways such as food and water, residential activity, and
certain post-application agricultural scenarios.  This list should not
be construed as a list of known or likely endocrine disruptors.

The allethrins are not among the group of 58 pesticide ais on the
initial list to be screened under the EDSP.  Under FFDCA sec. 408(p) the
Agency must screen all pesticide chemicals.  Accordingly, EPA
anticipates issuing future EDSP orders/data call-ins for all
registration review cases, including those for which EPA has already
opened a registration review docket for a pesticide ai. 

For further information on the status of the EDSP, the policies and
procedures, the list of 67 chemicals, the test guidelines and the Tier 1
screening battery, please visit our website:  http://www.epa.gov/endo/.

Timeline:

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

Registration Review for the Allethrins – Projected Registration Review
Timeline

Activities	Estimated Date

Opening the Docket

Open Docket and Public Comment Period	March 2010

Close Public Comment 	May 2010

Case Development	

Issue Final Work Plan (FWP)	August 2010

Issue Data Call-in (DCI)	April – June 2011

Data Submission1	April – June 2017

Open Public Comment Period for Preliminary Risk Assessments 	October –
December 2018

Close Public Comment Period	January - March 2019

Registration Review Decision

Open Public Comment Period for Proposed Registration Review Decision
April – June 2019

Close Public Comment Period	July - September 2019

Final Registration Review Decision & Begin Post-Decision Follow-up	2020

Total (years) 2	10

If the registrants choose to cite the 6 previously submitted DNT studies
as explained above, and if the results of the 90-day oral toxicity test
confirm that a new carcinogenicity study is not necessary, then this
time estimate will likely be shortened by approximately 3 years.   

An assessment of the potential cumulative risk from the pyrethroid class
of insecticides may impact this time estimate.

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 manner prior to issuing a final work plan (FWP) for the
allethrins.

Trade Irritants:

Through the registration review process, the Agency intends to solicit
information on trade irritants and, to the extent feasible, take steps
toward facilitating irritant resolution.  Growers and other stakeholders
are asked to comment on any trade irritant issues resulting from lack of
Maximum Residue Limits (MRLs) or disparities between U.S. tolerances and
MRLs in key export markets, providing as much specificity as possible
regarding the nature of the concern.

Water Quality:

The allethrins are 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://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d
?p_cause_group_id=885" 
http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?
p_cause_group_id=885 .  In addition, no Total Maximum Daily Loads (TMDL)
have been developed for the allethrins, based on information provided at

  HYPERLINK
"http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detai
l?p_pollutant_group_id=885&p_pollutant_group_name=PESTICIDES" 
http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail
?p_pollutant_group_id=885&p_pollutant_group_name=PESTICIDES .  More
information on impaired water bodies and TMDLs can be found at  
HYPERLINK "http://www.epa.gov/owow/tmdl/"  http://www.epa.gov/owow/tmdl/
.  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:  
HYPERLINK
"http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm" 
http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm )
in order to ensure they can be used quantitatively or qualitatively in
pesticide risk assessments.  

Environmental Justice:

EPA seeks to achieve environmental justice, the fair treatment and
meaningful involvement of all people, regardless of race, color,
national origin, or income, in the development, implementation, and
enforcement of environmental laws, regulations, and policies.  To help
address potential environmental justice issues, the Agency seeks
information on any groups or segments of the population who, as a result
of their location, cultural practices, or other factors, may have
atypical, unusually high exposure to the allethrins, compared to the
general population.  Please comment if you are aware of any
sub-populations that may have atypical, unusually high exposure compared
to the general population.

Other Information:

Stakeholders are also specifically asked to provide information and data
that will assist the Agency in refining the risk assessments, including
any species-specific ecological effects determinations.  The Agency is
interested in receiving the following information: 

confirmation on the following label information

sites of application

formulations

application methods and equipment

maximum application rates in units related to mass per unit area of
treatment zone

frequency of application, application intervals and maximum number of
applications per season

geographic limitations on use

use or potential use distribution use history

application timing (date of first application and application intervals)

typical interval (days)

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

Next Steps:

After the 60-day comment period closes, the Agency will review and
respond to any comments received in a timely manner, and then issue its
Final Work Plan (FWP) for the allethrins.

II.  FACT SHEET

The Pesticide Chemical (PC) codes and Chemical Abstract Service (CAS)
numbers for the allethrins:  

Bioallethrin- PC code 004003, CAS no. 260359-57-7

Esbiol- PC code 004004, CAS no. 28434-00-6

Esbiothrin- PC code 004007 (formerly 004003/004004), CAS no. 260359-57-7

Pynamin Forte- PC code  004005, CAS no. 231937-89-6

Registration review case number:  0437

Technical registrants:  Valent BioSciences Corporation (bioallethrin,
esbiol, esbiothrin) and Sumitomo Chemical Company, Ltd. (pynamin forte)

First registered for use in the U.S. in 1948.

The RED for the allethrins was completed on June 30, 2007.  A RED
Amendment was finalized on May 27, 2009.  

There are currently 228 end-use products and 4 technical products
registered.  

Since there are no food uses for the allethrins, there are no
tolerances.

Pesticide Re-evaluation Division Chemical Review Manager:  Molly
Clayton, clayton.molly@epa.gov            

Registration Division Contact:  Richard Gebken, gebken.richard@epa.gov 

Use & Usage Information:  (For additional details, please refer to the
Appendix A and SLUA documents in the allethrins docket.)

The allethrins are synthetic, type I pyrethroid insecticides.  They are
typically used as a “knock-down” agent.  A different, residual
pesticide is co-formulated with the allethrin in the end-use products to
kill the target pests.  Allethrins typically make up less than 1% of an
end-use product.

Commercial applications include space, broadcast and crack-and-crevice
treatments in a variety of commercial, industrial, residential, and
institutional sites.  Horticultural applications include foliar and
fogger treatment on non-food plants.  Residential uses include pest
control in homes and outdoor domestic structures, on gardens, and direct
application to pets.  Allethrins are also approved for use in commercial
animal premise (indoor) misting systems.  

Formulation types include:  pressurized liquids, ready-to-use liquids,
emulsifiable concentrates, liquid concentrates, pet shampoos and dips,
mosquito coils and mats.

Allethrin products are applied by power, mechanical, and commercial
sprayer; automatic misting system; aerosol can; and thermal fogger.  

Typical concentrations of allethrins ai in residential use products
range between 0.05 % and 0.25%.  Total release aerosol fogger
concentrations are typically 0.6% to 3% (total volume of the can versus
the area it is designed to treat).  Concentration of allethrins in mats
range from 7% and 24% and release ai into the air by heating the mat. 
Coils range from 0.1% to 0.3% in concentration and also release ai into
the air by burning of the coil (the ai is volatilized off of the coil
just behind the burning part of the coil.).  The maximum allethrin
product spray concentration for automatic misting systems is 0.05%.

Less than 30,000 lbs. of allethrins ais are marketed on average per
year.  Of the four allethrins, bioallethrin is the predominant form of
allethrin sold in the U.S.  Allethrins outdoor use generally totals less
than 10,000 pounds ai per year.  Pynamin forte is used exclusively in
the mat and coil formulations.  The majority of allethrins are used in
the consumer market (i.e., homeowner uses in space and surface sprays
for flying and crawling insects), and a small amount is sold into the
institutional/industrial market.

Recent and Pending Actions:  

On April 15, 2009 the EPA approved revised labels for the four
allethrins technical products.  The technical, or manufacturing-use,
products are used to formulate end-use products containing allethrins. 
The technical labels were revised to include the mitigation measures
specified in the 2007 RED, since no changes were made to the label
language specification when the RED was revised in 2009.  The statements
below now appear in the Directions For Use section of the allethrins
technical labels:

Only for formulation into an insecticide for: Domestic Indoor
(household); Domestic Outdoor (localized treatments only, including
total release foggers, space, spot and crack and crevice sprays);
Commercial/Industrial/Institutional Uses (space, general surface, spot,
and crack-and-crevice applications); and Greenhouse Ornamentals.

Not for formulation into end-use products with directions for use as an
application directly to pets.

Formulation into ready-to-use total release foggers with directions for
use outdoors is limited to a maximum of 1.5 ounces of product per
container.

Formulation into products with directions for use as a spot treatment in
residential settings is limited to a maximum 0.25% ai dilution strength.

Formulations with greater than 0.1% ai dilution strength must contain
directions for use limiting applications in indoor residential settings
to spot treatments only.  Indoor broadcast use must be prohibited.

Formulation into products with directions for use as a broadcast spray
outdoors is prohibited. Outdoor use is limited to spot treatments only.
(Note: outdoor broadcast use with ready-to-use total release foggers is
permitted).

Not for formulation into products for use in or on drainage systems,
golf course turf, airports/landing fields, uncultivated agricultural
areas, boat/ship hulls, and paved areas such as sidewalks and roads.

There is a pending action (petition # 6H5743) proposing a tolerance at
1.0 parts per million (ppm) in or on all food items for use in food
handling establishments (FHE).

Ecological Risk Assessment Status:

The following are key findings of the most recent ecological risk
assessments for the allethrins.   Please refer to the Registration
Review:  Preliminary Problem Formulation for Ecological Risk,
Environmental Fate, Endangered Species, and Drinking Water Assessment
for the Allethrins, located in the docket, for a detailed discussion of
previous ecological risk assessments.

The four registered allethrins ais are nearly identical except in the
ratios and amounts of the major isomers, which are assumed to be
equipotent.  Therefore, data have been bridged between the allethrins
databases in previously conducted ecological assessments.

The allethrins have a tendency to sorb to surface soils, particularly in
soils that are not low in organic matter, and synthetic pyrethroids as a
class tend to photodegrade fairly quickly.  

Allethrins are early-generation pyrethroids and differ structurally from
more recently developed pyrethroids, which have structural modifications
that make them more persistent.  Allethrins are among the least
persistent of pyrethroids.

There are no agricultural uses of allethrins.  A small amount of
allethrins ai is used per application to residential or commercial
outdoor treatment sites, and the methods of application (i.e., spray
cans, mosquito coils, patio yard and foggers) do not result in large
outdoor exposure areas.  

The most recent ecological screening assessment (2007) determined that
the potential for ecological risk from use of allethrins products is
limited or eliminated by the application methods described on the
product labels. 

Human Health Risk Assessment Status:

The following are key findings of the most recent human health risk
assessments for the allethrins.  Please refer to The Allethrins: 
Registration Review Scoping Document for Human Health Assessments,
located in the docket, for a detailed discussion of previous human
health risk assessments.

The most recent comprehensive human health risk assessment was completed
on June 27, 2007 in support of reregistration and a petition to
establish a tolerance for use in FHEs.

An updated occupational assessment was completed February 17, 2009 to
include risk estimates for use of allethrins in animal premise automatic
misting systems employed in commercial and industrial horse barns, dog
kennels, and zoo quarters.

Past allethrins risk assessments rely in part on data in generic
databases from studies in which adult human subjects were intentionally
exposed to a pesticide to determine their dermal and inhalation
exposure.  Many such studies, involving exposure to many different
pesticides, comprise generic pesticide exposure databases such as the
Non-dietary Exposure Database and the Pesticide Handler Exposure
Database.  EPA has reviewed all the studies supporting these
multi-pesticide generic exposure databases, and has found no clear and
convincing evidence that the conduct of any of them was either
fundamentally unethical or significantly deficient relative to the
ethical standards prevailing at the time the research was conducted. 
There is no regulatory barrier to continued reliance on these studies,
and all applicable requirements of EPA’s Rule for the Protection of
Human Subjects of Research (40 CFR Part 26) have been satisfied.

Hazard Characterization:

lack an α-cyano substituent).  Pyrethroids are neurotoxicants which act
by prolonging the opening of the sodium channel in nervous tissue,
resulting in a hyperexcitable state.  Neurotoxicity in rats of type I
pyrethroids is characterized as tremor, prostration, enhanced startle
response, and aggressive behavior.  Similar signs of neurotoxicity were
observed in the guideline studies conducted with allethrins.

Since the four registered allethrins ais are structurally similar
differing only in the relative proportions of stereoisomers, and they
caused similar types of neurotoxicity and liver toxicity at generally
similar doses, one set of risk assessment endpoints covering all four
chemicals was selected from the combined database.

In the most recent comprehensive human health risk assessment (June
2007), the Agency applied a database uncertainty factor (UFDB) of 10x
for non-occupational inhalation and incidental oral exposures due to the
lack of a DNT study. 

EPA has recently determined that, as an alternative to the generation
and submission of a new DNT study, registrants may instead choose to
cite to the six previously submitted DNT studies for pyrethroid
pesticides.  The six chemicals with acceptable DNTs include: bifenthrin,
cyfluthrin, cyhalothrin, cypermethrin (zeta), fenpropathrin, and
deltamethrin.  Given the similarity of certain results across all these
studies, EPA has concluded that, when considered together, these studies
provide sufficient information for EPA to determine that the conclusions
are applicable to all pyrethroids.  EPA will therefore consider citation
of all of the six studies as a substitute for generating a single new
study for a given pyrethroid chemical.  

The cancer classification for esbiothrin is "suggestive evidence of
carcinogenicity, but not sufficient to assess human carcinogenic
potential."  

Dietary (Food and Drinking Water):

	

The Agency has not previously conducted a drinking water assessment for
the allethrins because their use is limited to indoor non-food use
settings and outdoor use is limited to spot treatments (e.g., wasp and
hornet sprays, foggers).  

An acute and chronic dietary (food only) risk assessment was performed
in the 2007 assessment in support of the proposed FHE use.  The acute
and chronic dietary risk estimates were below the Agency’s level of
concern (LOC).  

       

Residential:

In the 2007 risk assessment, risk estimates for all residential handler
exposure scenarios assessed were above the Agency’s target margin of
exposure (MOE) of 1000 after mitigation measures identified in the RED
were incorporated, and therefore, were not of concern to the Agency.

For residential post-application exposure scenarios, the MOEs were
greater than the target MOE of 1000 after mitigation measures identified
in the RED were incorporated, except for inhalation exposures from yard
and patio total release foggers.  However, the Agency does not
anticipate a risk of concern from this use due to the product use
pattern and dose spacing methodology in the inhalation study on which
the risk estimate is based.

Aggregate:

An aggregate exposure assessment considers food, drinking water, and
residential exposures from three major exposure routes: oral, dermal,
and inhalation.  The residential component of the allethrins aggregate
assessments included only incidental oral exposure.  Inhalation exposure
was not aggregated because the endpoint for inhalation exposure was
based on a different effect (neurotoxicity) and no endpoints were
identified for dermal exposure.  Drinking water dietary exposure was
also not aggregated because a drinking water has not been conducted due
to the limited nature of allethrins’ outdoor use.  Aggregate risk was
calculated for combined food (from the pending FHE use) and residential
(incidental oral) exposure.  The estimated allethrins aggregate risks
are below the Agency’s LOC.   

Occupational:

All occupational handler and post-application risk estimates were above
the Agency’s target MOE of 100 after mitigation measures identified in
the RED were incorporated, and therefore, were not of concern to the
Agency.

Cumulative:

The allethrins are members of the pyrethroid class of insecticides. 
This class also includes permethrin, cypermethrin, cyfluthrin,
tau-fluvalinate, bifenthrin, fenpropathrin, and lambda-cyhalothrin,
among others.  EPA developed a draft science policy document on the
proposed common mechanism of toxicity for naturally-occurring pyrethrins
and synthetic pyrethroids (Proposed common mechanism grouping for the
pyrethrins and pyrethroids, draft, May 19, 2009;   HYPERLINK
"http://www.regulations.gov/search/Regs/home.html#documentDetail?R=09000
064809a62df" 
http://www.regulations.gov/search/Regs/home.html#documentDetail?R=090000
64809a62df  ).  This document was supported by the FIFRA Scientific
Advisory Panel (SAP) and EPA will finalize the policy document on the
pyrethroid common mechanism of toxicity taking into account the SAP
comments.  Pesticides with a common mechanism of toxicity are subject to
cumulative risk assessment under the FQPA.  Research is on-going by
EPA’s Office of Research and Development (ORD) to make improvements to
the SHEDS probabilistic exposure model, which are important for the
cumulative risk assessment.  EPA ORD is also developing
physiologically-based pharmacokinetic models for several pyrethroids. 
The status of both of these research modeling efforts will be reviewed
by the FIFRA SAP in July, 2010.  For information regarding EPA’s
efforts to evaluate the risk to pyrethroids, see   HYPERLINK
"http://www.epa.gov/pesticides/cumulative/" 
http://www.epa.gov/pesticides/cumulative/  .

Incidents:

Ecological:

The Agency consulted the Avian Incident Monitoring System (AIMS), the
Ecological Incident Information System (EIIS, version 2.1), and the
Aggregate Incident Reports (AIR) database for reports of ecological
incidents. 

There are currently no reported incidents involving allethrins listed in
the AIMS database. 

  SEQ CHAPTER \h \r 1 The EIIS database identified 1 ecological incident
involving a previously registered allethrins ai (PC Code 004001) that
was determined to be an act of sabotage (i.e., it was the result of
intentional misuse).  This ai was cancelled in 1992.

The AIR is a system whereby the Agency tracks certain types of incidents
that pesticide registrants report as aggregate counts of incidents
occurring per product per quarter.  Ecological incidents reported in
aggregate reports include those categorized as “minor fish and
wildlife”, “minor plant”, and “other non-target” incidents. 
“Other non-target” incidents include reports of adverse effects to
insects and other terrestrial invertebrates.  For the allethrins, 13
incidents were identified; all were minor terrestrial plant incidents
involving bioallethrin (PC Code 004003) and occurred between 1995 and
2005.  Unless additional information on these aggregated incidents
becomes available, they will be assumed to be representative of
registered uses of the allethrins in the risk assessment.  Because the
number of documented incidents in the available incident databases is
believed to be a small fraction of total ecological incidents caused by
pesticides for a variety of reasons, absence of reports does not
necessarily provide evidence of an absence of incidents.

Human Health:

EPA consulted the following two incident databases to prepare incident
reports for the four allethrins ais in preparation of the registration
review docket opening: OPP Incident Data System (IDS) and the Centers
for Disease Control and Prevention/National Institute for Occupational
Safety and Health (CDC/NIOSH) Sentinel Event Notification System for
Occupational Risk (SENSOR).  

In IDS, 26 single chemical incidents were reported between 2002 and
2009, i.e., there were 26 incidents in which the end-use product
associated with the incident contained only one of the four allethrins
ais and was not a product co-formulated with another ai as is common. 
An IDS query was also conducted for incidents involving multi-ai
products containing allethrins, which identified a moderately large
number of incidents.   Since these incidents involve more than one
active ingredient, there is considerable uncertainty as to whether the
incidents reported are a direct result of exposure to an allethrin ai or
another ai.

In NIOSH SENSOR, 177 cases were reported between 1998 and 2005 involving
esbiol or pynamin forte.  Cases reported for esbiol or pynamin forte
alone and where exposure was determined to be definite, probable, or
possible were reviewed in detail, as these cases provide more reliable
information about the potential effects of exposure to allethrins. 
Using these selection criteria, 2 cases were identified.  The symptoms
in these 2 cases included neurotoxic, dermal, and ocular effects.  Both
cases were classified as low severity.  NIOSH SENSOR was not searched
for bioallethrin or esbiothrin; however, this search will be conducted
during the development of the FWP.  Of the 175 NIOSH SENSOR cases in
which esbiol or pynamin forte are not the only ai, there were 144 cases
classified as low severity, 25 cases classified as moderate severity, 2
cases classified as high severity, 3 cases were considered unlikely to
be related to the pesticide product, and 3 cases were fatal.  All of the
high and fatal severity cases were cases of misuse; 4 were ingestion of
the product and the fifth was a case of dermal contact.

In general, both the IDS and NIOSH SENSOR queries resulted in moderately
large numbers of case reports.  However, most of these incidents were of
low severity and no patterns or trends were discerned among the reported
cases.  Subsequently, it is not clear human incident data warrant
further analysis for the risk assessment and/or risk management of
allethrins.  The Agency will continue to monitor the incident
information and if a concern is triggered, additional analysis will be
included in the risk assessment.

Tolerances and International Harmonization: 

No Codex, Canadian, or Mexican maximum residue limits (MRLs) have been
established for allethrins. 

DCIs:

The RED GDCIs for the four allethrins were issued on December 18, 2009. 
The following guideline studies were required:

GLN 870.6300 – DNT

GLN 875.1400 – Inhalation indoor exposure

GLN 830.7050 – UV/Visible absorption

GLN 870.7800 – Immunotoxicity

Labels:

 

A list of registration numbers for the allethrins can be found in the
docket and the labels for the allethrins can then be obtained from the
Pesticide Product Label System (PPLS) website:    HYPERLINK
"http://oaspub.epa.gov/pestlabl/ppls.home" 
http://oaspub.epa.gov/pestlabl/ppls.home .

 If appropriate plant incident data are submitted, the Agency may
consider a waiver for the plant toxicity tests. 

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