2 

### Amitraz Final Work Plan

Introduction

This is the Environmental Protection Agency’s (EPA’s) Final Work Plan (FWP) for the registration review of amitraz. The FWP includes the expected registration review timeline. The FWP also addresses public comments received concerning the Preliminary

Work Plan in the Summary Document , which was posted in the amitraz registration review docket (EPA-HQ-OPP-2009-1015), a nd any other comments concerning the initial docket postings. The Summary Document provided information on what EPA knows about the pesticide and what additional ri sk analyses and data or information the Agency believes are needed to make a registration review decision.

The Agency is implementing the new registra tion review program and will review each registered pesticide every 15 years to determin e whether it continues to meet the Federal Insecticide, Fungicide, and R odenticide Act (FIFRA) standard for registration. Changes in science, public policy, and pesticide use practices will occur over time. The registration review program is intended to ma ke sure that, as the ability to assess risk evolves and as policies and pract ices change, all registered pe sticides continue to meet the statutory standard. The public phase of registration review begins when the initial docket is opened for each case. Inform ation on this program is provided at: http://www.epa.gov/oppsrr d1/registration_review/

.

Amitraz is a formamidine insecticide/miticide, which is currently registered for use on cattle, swine, and canines to control various in sects such as ticks, li ce, and mange mites. The mode of action for amitraz is through a mechanism which causes an increase in nerve activity within arachni ds; in addition, it also cause s toxic effects through the octopamine receptor (which causes the insect/m ite to release their b ite (on host animals) before falling off the host animal and dying). There are two technical registrations and three end-use product registrati ons containing amitraz.

Comments Received on Preliminary Work Plan

Comments were received from the Physic ians Committee for Responsible Medicine (PCRM) regarding the amitraz Preliminary Wo rk Plan (PWP) during the 60-day public comment period, which began on March 31, 2010 and closed on June 1, 2010. This comment did not change the work plan or ti meline established in the PWP. In addition, through the PWP, EPA solicited comments on three specific topics: environmental justice, water body impairment, and trade irr itants. No comments or information were received during the comment period concerning these topics.3 Risk Assessment and Data Needs

Ecological Risk:

• The most recent ecological risk assessment was completed in January of 1994 in support of the amitraz Reregistration Eligibility Decision (RED).

• The Agency has not conducted a risk assessment that supports a complete endangered species determination. The eco logical risk assessment planned during registration review will allow the Agency to determine whether the use of amitraz has “no effect” or “may affect” federally listed threatened or endangered species (listed species) or their designated cr itical habitats. When an assessment concludes that a pesticide’s use “may aff ect” 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 Service (the Se rvices), as appropriate.

• The Agency anticipates needing the fo llowing data in order to conduct an endangered species and non-target ecologi cal risk (and possibly drinking water)

assessment for amitraz.

o (GLN 835.1240) Absorption/de sorption – degradates only

o (GLN 850.2100) Avian oral toxi city – Passerine species

o (GLN 850.4100) Terrestrial Plant toxi city Tier 1 seedling emergence

o (GLN 850.4150) Terrestrial Plant t oxicity Tier 1 vegetative vigor

o (GLN 850.5400) Aquatic Plant Growth: algae

• For more information regarding the stat us and review of ecological fate and effects of amitraz, please refer to the document: Registration Review - Problem Formulation for Ecological Risk and Environmental Fate, Endangered Species, and Drinking Water Assessments for Amitraz in the amitraz registration review docket (EPA-HQ-OPP-2009-1015)

.

Human Health Risk:

• The most recent comprehensive risk assessment for amitraz was conducted in 1994 to support the Reregistration Eligibil ity Decision (RED). The most recent non-comprehensive human health assessmen t (dietary and resi dential exposures only) for amitraz was completed in 2006 to support the Tolerance Reassessment Eligibility Decision (TRED) for amitraz.

• Based upon the anticipated data requiremen ts, the toxicological endpoints may be revised during the registration review of amitraz.4 • The Agency anticipates conducting an o ccupational handler assessment but does not anticipate conducting a post-applic ation occupational as sessment during the registration review of amitraz (based on mi nimal worker interactions with treated animals in a professional environment).

• The Agency anticipates conducting a ne w aggregate assessment, which will

include both food and residential data.

• The Agency’s residue chemistry database for amitraz is complete. However, the Agency anticipates revising the current pl ant and livestock to lerance expressions in 40 CFR §180.287 to clarify (i) that th e tolerance covers metabolites and degradates of amitraz and (ii) that compliance with the specified tolerance levels is to be determined by measuring only the specific compounds mentioned in the tolerance expression to reflect current methodology and policy.

• A new drinking water assessment may be conducted during registration review, which would include any updated hazard information.

• Use of dog collars impregnated with amitraz is anticipated to re sult in residential handler/applicator and post-application exposures. New toxi city studies may identify new endpoints for assessment a nd new residential exposure assessment SOPs are expected to be in place by the time the amitraz human health risk

assessment is conducted. Therefore th e Agency plans to conduct a revised residential handler and post -application risk assessment during the registration

review of amitraz.

• The Agency anticipates requiring the fo llowing studies, in accordance with the revised 40CFR Part 158, to conduct a comprehensive human health risk assessment for the registration review of amitraz.

o (GLN 870.3100) Sub-chronic (90-da y) Oral Toxicity Study in Rats

o (GLN 870.3150) Sub-chronic (90-day) Oral Toxicity Study in Dogs

o (GLN 870.3200) 21/28-Day Dermal Toxicity

o (GLN 870.3250) Sub-chronic ( 90-day) Dermal Toxicity

o (GLN 870.3465) Sub-chronic (90-da y/28-day) Inhalation Toxicity

o (GLN 870.3700) Pre-Natal Devel opmental Toxicities – Rabbit

o (GLN 870.6200a) Neurotoxicity Battery (acute studies)

o (GLN 870.6200b) Neurotoxicity Ba ttery (sub-chronic studies)

o (GLN 870.6300) Developmen tal Neurotoxicity Study

o (GLN 870.7800) Immunotoxicity

• In response to a data call-in (DCI) fro m the amitraz TRED, the registrants have submitted draft protocols for a modified one-generation reproduction study (GLN 870.3800) which includes pertinent m easurements for developmental neurotoxicity and possible immunotoxic ity parameters. If this study is5 successfully completed, it may be used to satisfy data needs for neurotoxicity, reproduction and immunotoxicity studies.

• For more information on the status and re view of the human health effects of amitraz, please refer to the document: Updated Amitraz Human Health Assessment Scoping Document in Support of Registration Review in the amitraz registration review docket (EPA-O PPTS-OPP-2009-1015) for a detailed discussion of previous human health assessments.

Timeline

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

Registration Review for Amitraz Projected Registration Review Timeline

Milestone Date Opening the Docket Open Docket & Public Comment Period for Amitraz March 2010 Close Public Comment Period May 2010 Case Development Final Work Plan Sept. 2010 Issue DCI Apr. – June 2011 Data Submission Apr. – June 2013 Open Public Comment for Preliminary RA Oct. – Dec. 2014

Close Public Comment Period Jan. – Mar. 2014 Registration Review Decision Open Public Comment for Proposed Regist ration Review Decision Apr. – June 2015 Close Public Comment Period July – Sept. 2015 Final Reg. Review Decision and begin post-decision follow-up 2016

Total 6 years

Summary of Comments Receive d During Docket Opening

The amitraz registration review docket wa s open for a 60-day public comment period which began on March 26, 2010. During that time, the Physicians Committee for Responsible Medicine (PCRM) submitted comments to the Agency which are

summarized below. The comments did not chan ge the work plan or timeline set out in the preliminary work plan. Consequently, this document makes final the work plan for the amitraz registration review process.

Comment from PCRM The Physicians Committee for Responsible Medicine (PCRM) submitted comments regarding a series of animal st udies which were identified as data requirements in the Summary and Scoping documents. PCRM indicated that data6 may already exist either with the technical registrants or othe r sources that could fulfill some of the Agency’s data requirements, which would reduce animal testing and costs.

EPA Response The Agency is committed to reduce, re fine and ultimately replace the use of animals for toxicity testing. As a result, the Agency is worki ng with the technical registrants to develop a very effici ent “extended one-generation reproduction protocol” which will greatly minimize repl ication of testing and animal usage. This protocol will combine multiple tests into one combined comprehensive study which will negate the need for additional animal testing. The toxicologicol studies that will be combined include: repr oduction, immununotoxic ity, neurotoxicity, developmental, clinical chemistry, hematol ogy, urinalysis, oral t oxicity, and etc. Furthermore, the Agency has reviewed the references submitted by PCRM, the Agency believes that the data originally required in the HED Scoping is still necessary to fulfill EPA’s obligati ons under FIFRA, FFDCA and FQPA.

For detailed responses to comments recei ved from PCRM, see the document entitled “Amitraz: Response to PCRM Comments on Data Requirements (09/10/10)” in the amitraz registration review docket (EPA-OPPTS-OPP-2009-1015).

Next Steps

The Agency will develop a data call-in (DC I) notice for the data gaps listed under the

“Risk Assessment and Data Needs” section above.

Both an ecological risk assessment, wh ich will include an endangered species assessment, and a human health risk assessm ent will be conducted as detailed in the

“Risk Assessment and Data Needs” section above.