1 Docket Number: EPA-HQ-OPP-2010-0022 www.regulations.gov



## The Allethrins Final Work Plan Registration Review August 20103 THE ALLETHRI NS 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 exp ected 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 re gistration review doc ket (EPA-HQ-OPP-2010- 0022), and any other comments concerni ng the initial docket postings. The Summary Document provided information on what EPA k nows 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 Rode nticide Act (FIFRA), and will re view 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 do cket is opened for each case. Information on this program is provided at: http://www.epa.gov/oppsrr d1/registration_review/

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The allethrins (case 0437) are members of the pyreth roid class of insecticides. The allethrin series includes bioallethrin, esbiol, esbiot hrin, and pynamin forte. They are used to control flying and crawling insects in a number of commercial, horticultural and re sidential applications. Common product forms include wasp and hornet aerosols; yard and patio foggers; flying in sect killer aerosols; total release aerosols (in door foggers); mosquito repellants (mats and coils); space sprays; and crawling insect kille r aerosols. The allethrins are regist ered for both indoor and outdoor uses. Outdoor products are applied to localized treatment areas and ar e 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; al l food uses were cancelled in 2004 (69 FR 188).

The allethrins were the subjects of a Reregi stration Eligibility Decision (RED), which was completed on June 30, 2007. Subsequent to publication of the RED, the techni cal 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, th e Agency updated the allethrins occupational and residential risk assessment to incl ude 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

.4 This comment and the Agency’s response are incl uded 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 c oncerning 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 re vise the human health ri sk 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 asse ssment 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 endangere d species (listed species) or their designated

critical habitats. When an assessment conclude s that a pesticide’s use “may affect” a listed species or its designated critical habitat, th e Agency will consult with the U.S. Fish and

Wildlife Service and/or National Marine Fisherie s Services (the Services), as appropriate.

• An updated ecological assessment will be condu cted 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 – Seedli ng 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

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

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

tests.5 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 as sessment 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 aggregat e risk, taking into accoun t anticipated changes to toxicological endpoints, safety factors, expos ure values, and applicab le standard operating procedures.

• An immunotoxicity study (GLN 870.7800), an inhalation indoor exposure study ( 875.1400) , a UV/Visible absorption study (870.78 00), and a developmental neurotoxicity (DNT) study (GLN 870.6300) were required in the allethrins reregist ration generic data call-in (GDCI) issued in December 2009. The immunotoxicity and inhalati on 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 pyret hroid 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, pyr ethroid registrants may instead choose to cite the six previously submitted DNT studies fo r pyrethroid pesticides. The Agency is also investigating the need for additional experime ntation, 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, a nd 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/reevalua tion/pyrethroids-pyrethrins.html

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• During the registration review human health scoping process for the allethrins, several

additional uncertainties in the toxicity data ba se were identified.

o Dosing in the submitted mouse carcinogenicity study (MRID 41519804) with esbiothrin was considered inadequate and was not s upported by the 8-week range-finding study. Therefore, a 90-day oral toxi city 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 ne w 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.6 • The Agency will require the following data in th e 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 fo llowing receipt of requi red 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, cyflut hrin, tau-fluvalinate, bifenthr in, fenpropathrin, and lambdacyhalothrin, among others. EPA developed a dr aft science policy document on the proposed common mechanism of toxicity for naturally-occurring pyrethri ns and synthetic pyrethroids (Proposed common mechanism grouping for the pyrethrins and pyrethroids, draft, May 19, 2009; http://www.regulations.gov/search/R egs/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/R egs/home.html#documentDetail?R=0900006480a1f8d7 ). EPA will finalize the policy document on th e pyrethroid common mechanism of toxicity taking into account the SAP comm ents. Pesticides with a comm on mechanism of toxicity are subject to cumulative risk assessment under the FQPA. Research is on-going by EPA’s Office of Research and Developm ent (ORD) to make improvements to the Stochastic Human Exposure and Dose Simulation (SHEDS) probabilis tic 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 re garding EPA’s efforts to evaluate the risk to pyrethroids, see http://www.epa.gov/oppsrrd1/reevaluati on/pyrethroids-py rethrins.html.

• Please refer to Human Health Scoping Document in Support of Registration Review for the Allethrins, located in the docket, for a detailed discu ssion of the anticipate d 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 su bstances (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 effect s as the Administrator may designate.” The EDSP employs a two-tiered approach to making the statutorily required determinations . Tier 1 consists of7 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 a ny, 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 es tablish a quantitative relationship between the dose and the E, A, or T effect.

Between October 2009 and February 2010, EPA issued te st orders/data call-ins for the first group of 67 chemicals, which contains 58 pesticide active ingredie nts (ais) and 9 inert ingred ients. This list of chemicals was selected based on the potential fo r 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 know n 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 cal l-ins for all registration review cases, including those for which EPA has already opened a regi stration review docket for a pesticide ai.

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

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Timeline :

EPA has created the following estimated timeline fo r 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 Submission 1 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 20198 Registration Review for the Allethrins – Projected Registration Review Timeline

Activities Estimated Date
Final Registration Review D ecision & Begin Post-Decision Follow-up 2020

Total (years) 2 10
1. If the registrants choose to cite the six previously subm itted 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 th e 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. Th is 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 – Seedli ng Emergence Phytotoxicity (Tier II), and GLN 850.4150 – Vegetative Vigor Ph ytotoxicity (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 alleth rins uses that have the potentia l for direct contact with plants were canceled as stated in the problem formula tion document (drainage syst ems, golf course turf, wide area/general outdoor treatm ent, 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 a nd 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 proh ibited. 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 landscap e areas; wasp and hornet sprays (3 seconds spray on the nest) and spot applications to trees to kill tent caterpillars, and mosquito re pellent mats. Therefore, Valent Bioscience Corporation, the techni cal registrant of allethrins, reque sts that these studies be waived for lack of relevance based on the use patter n. Similarly, GLN 850.3030 – Honey Bee Toxicity of Residues on Foliage is not applicable for the sa me reasons indicated above (very limited direct contact with plant foliage a nd direct spray on plants).”

EPA Response:

As stated in the Problem Formulation for the al lethrins, registrants have reported 13 aggregated terrestrial plant incidents for a llethrins 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. In9 the absence of additional informati on on the remaining aggregated plan t incidents, it is assumed that these incidents were also associated with currently registered uses of alleth rins. Therefore, based on the available incident data, there is evidence that at least some of the current uses that Valent describes as having “extremely limite d” contact with vegetation ( i.e ., wasp and hornet sprays) can

cause adverse effects to non- target terrestrial plants. Without toxicity data fr om terrestrial plants it will not be possible to determine a threshold of poten tial effects to plants (including those that are federally listed as endangered or th reatened) from allethrins use and ri sks to terrestrial plants will be assumed. Therefore, if future endangered species risk assessments are perf ormed without these data, the Agency would have to presume risk to non-target terrestrial plants from th e 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 thes e data will limit the flexibility the Agency and registrants have in coming into compliance with th e Endangered Species Act and could result in use

restrictions for the allethrins that are unnecessarily severe.

Regarding GLN 850.3030 (honey bee toxi city 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 LD 50 <11 μg/bee and the use pattern(s) indicate(s) that honey bees may be exposed to the pe sticide. The acute contact LD 50 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 prec autionary honey bee language is not on allethrins product labels, the Ag ency requires a honey bee toxicity of residues on foliage study. The Agency will assume risks to terrestrial inverteb rates 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 E ffects 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 ri sk assessment for the allethrins.

Studies To Be Included in DCI:

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

table below.10 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, w ith 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.