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

www.regulations.gov

The Allethrins Final Work Plan 

Registration Review 

August 2010 

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 THE ALLETHRINS FINAL WORK PLAN 

Introduction: 

This is the Environmental Protection Agency’s (EPA’s) Final Work Plan for the registration review 

of the allethrins. This work plan includes the expected registration review timeline. The work plan 

also addresses public comments received concerning the Preliminary Work Plan in the Summary 

Document, which was posted in the allethrins registration review docket (EPA-HQ-OPP-2010-

0022), and any other comments concerning the initial docket postings. The Summary Document

provided information on what EPA knows about the pesticide and what additional risk analyses and 

data or information the Agency believes are needed to make a registration review decision. 

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. 

Changes in science, public policy, and pesticide use practices will occur over time. 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. The public phase 

of registration review begins when the initial docket is opened for each case. Information on this 

program is provided at: http://www.epa.gov/oppsrrd1/registration_review/. 

The allethrins (case 0437) 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 products 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. 

Comments Received on Preliminary Work Plan: 

One comment was received during the 60-day public comment period on the Summary Document. 
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This comment and the Agency’s response are included in this document, and, as described, the 

comment did not result in changes to the preliminary work plan set out in the Summary Document. 

In the Summary Document, EPA also solicited comments on three specific topics: environmental 

justice, water body impairment, and trade irritants. No comments or information were received 

during the comment period concerning these issues. 

Anticipated Risk Assessment and Data Needs:

The Agency will conduct a comprehensive 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. 

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 will be conducted to incorporate new data and any 

relevant changes to risk assessment methodologies. 

• The Agency will require the following data in order to conduct a complete ecological risk 

assessment, including an endangered species assessment, for all uses: 

o Guideline number (GLN) 850.4100 – Seedling Emergence Phytoxicity (Tier II) 1 

o GLN 850.4150 – Vegetative Vigor Phytoxicity (Tier II)1

o GLN 850.3030 – Honey Bee Toxicity of Residues on Foliage 

o

• 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. 

 

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

tests. 
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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 will not conduct a drinking water assessment for the allethrins, since registered 

outdoor use is limited to spot treatment only. 

• During registration review, the Agency will conduct 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 are due in June 2011, the 

UV/Visible absorption data are due in August 2010, and the DNT data are 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) 

was held in July 2010 to discuss this issue, and a report of the SAP should be provided to the 

Agency in several months. For more information on the pyrethroid DNT requirement, see 

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. 

o 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. 

o A micronucleus assay with esbiothrin was previously submitted and classified as 

unacceptable. These data are 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. 
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• The Agency will require the following data in the registration review DCI for the allethrins in 

order to conduct a complete human health risk assessment: 

o GLN 870.5395 – In Vivo Cytogenetics 

o GLN 870.3100 – 90-day Oral Toxicity in Rodents 

o 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 lambdacyhalothrin, 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; 

http://www.regulations.gov/search/Regs/home.html#documentDetail?R=09000064809a62df

). This document was supported by the FIFRA Scientific Advisory Panel (SAP) and is 

available in the docket 

(http://www.regulations.gov/search/Regs/home.html#documentDetail?R=0900006480a1f8d7

). 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 were reviewed by the FIFRA SAP in July, 2010, and the Agency anticipates 

receipt of the Panel’s report. For information regarding EPA’s efforts to evaluate the risk to 

pyrethroids, see 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 
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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 completion of the registration review for the 

allethrins. 

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 
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Registration Review for the Allethrins – Projected Registration Review Timeline 

Activities Estimated Date 

Final Registration Review Decision & Begin Post-Decision 

Follow-up 2020 

Total (years) 2 10 

1. If the registrants choose to cite the six 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. 

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

estimate.

Summary of Comments and Agency Responses: 

The allethrins registration review docket was open for a 60-day comment period beginning on March 

31, 2010. During the comment period, the technical registrant submitted one comment on the 

ecological data requirements. This comment and the Agency’s response are below. This comment 

did not result in a change to the allethrins work plan. 

Comment from Valent BioSciences Corporation: 

“In the anticipated risk assessment data needs, the Agency indicated that the following data would be 

required: Guideline number (GLN) 850.4100 – Seedling Emergence Phytotoxicity (Tier II), and 

GLN 850.4150 – Vegetative Vigor Phytotoxicity (Tier II). The Problem Formulation document 

indicated that these requirements stem from 13 incidents reports between 1995 and 2005. During the 

re-registration process, many allethrins uses that have the potential for direct contact with plants 

were canceled as stated in the problem formulation document (drainage systems, golf course turf, 

wide area/general outdoor treatment, airports/landing fields, uncultivated agricultural areas, paved 

areas). The current allethrins outdoor uses as stated in table 3.2 consist of wasp and hornet 

nest/aerosol spray, yard and patio/fogger, mosquito repellant/mat and localized spot treatments of 

outdoor areas. These uses involve direct sprays to plants but only as spot treatments of localized 

areas. Broadcast applications to plants and other vegetation are prohibited. Therefore, contact with 

vegetation is extremely limited. Examples of these uses involve foggers that protect a patio area (3 

second spray) during which surrounding vegetation may be sprayed, limited spot treatments of lawns 

and ornamental plants in landscape areas; wasp and hornet sprays (3 seconds spray on the nest) and 

spot applications to trees to kill tent caterpillars, and mosquito repellent mats. Therefore, Valent 

Bioscience Corporation, the technical registrant of allethrins, requests that these studies be waived 

for lack of relevance based on the use pattern. Similarly, GLN 850.3030 – Honey Bee Toxicity of 

Residues on Foliage is not applicable for the same reasons indicated above (very limited direct 

contact with plant foliage and direct spray on plants).” 

EPA Response: 

As stated in the Problem Formulation for the allethrins, registrants have reported 13 aggregated 

terrestrial plant incidents for allethrins that occurred from 1995 until 2005. At least eight of the 

reported plant incidents (62%) were the result of wasp and hornet spray applications of allethrins. In 
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the absence of additional information on the remaining aggregated plant incidents, it is assumed that 

these incidents were also associated with currently registered uses of allethrins. Therefore, based on 

the available incident data, there is evidence that at least some of the current uses that Valent 

describes as having “extremely limited” contact with vegetation (i.e., wasp and hornet sprays) can 

cause adverse effects to non-target terrestrial plants. Without toxicity data from terrestrial plants it 

will not be possible to determine a threshold of potential effects to plants (including those that are 

federally listed as endangered or threatened) from allethrins use and risks to terrestrial plants will be 

assumed. Therefore, if future endangered species risk assessments are performed without these data, 

the Agency would have to presume risk to non-target terrestrial plants from the use of allethrins. As 

a result, use of the allethrins and their formulated products may need to be restricted in areas where 

listed species could be exposed. The lack of these data will limit the flexibility the Agency and 

registrants have in coming into compliance with the Endangered Species Act and could result in use 

restrictions for the allethrins that are unnecessarily severe. 

Regarding GLN 850.3030 (honey bee toxicity of residues on foliage), the Agency reiterates that 

under the 40 CFR Part 158 (July 1, 2009) guideline requirements, data on honey bee toxicity of 

residues on foliage are required when the acute honey bee contact LD50 <11 μg/bee and the use 

pattern(s) indicate(s) that honey bees may be exposed to the pesticide. The acute contact LD50 for 

allethrin is 3.4 μg a.i./bee (allethrin, MRID 162751), and there is a potential for exposure to bees 

from the currently registered uses. Therefore, the lack of information on toxicity of residues on 

foliage to the honey bee is identified as a data gap. Since precautionary honey bee language is not 

on allethrins product labels, the Agency requires a honey bee toxicity of residues on foliage study. 

The Agency will assume risks to terrestrial invertebrates if honey bee toxicity of residues on foliage 

data are not submitted. As mentioned above, lack of these data could result in unnecessarily severe 

restrictions for allethrins in order to comply with the Endangered Species Act. 

Availability of Agency Response to Public Comments: 

The comment (above) received during the public comment period has been addressed by the 

Environmental Fate and Effects Division’s document Review of the Data Waiver Request for 

Allethrins and Terrestrial Plant and Honey Bee Toxicity Data Requirements for Registration 

Review, dated June 29, 2010. This document is available in the allethrins docket (EPA-HQ-OPP2010-0022).

Next Steps: 

o The Agency plans to issue a DCI in mid-2011, requiring the allethrins studies needed to 

complete both the ecological and human health risk assessments.

o The Agency will conduct an ecological risk assessment, including an endangered species 

assessment, and a human health risk assessment for the allethrins.

Studies To Be Included in DCI:

The studies that will be included in the registration review DCI for esfenvalerate are listed in the 

table below. 
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Guideline 

Number Data Requirement Test Material 

Estimated 

Timeframe 

850.4150 Vegetative Vigor (Tier II*) TEP 12 

850.4100 Seedling Emergence (Tier II*) TEP 12 

850.3030 Honey Bee Toxicity of Residues on Foliage TEP 12 

870.5395 In Vivo Cytogenetics TGAI 9 

870.3100 90-day Oral Toxicity in Rodents TGAI 24 

870.4200 Carcinogenicity Study in Mice TGAI 48 

*

Registrants may opt to conduct a Tier I study, with the understanding that any adverse effects 

(even if <25%) may necessitate a Tier II study. A Tier II study will enable the Agency to conduct an 

endangered species assessment for nontarget plants.