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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), 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 new registration review program and will review each 

registered pesticide every 15 years to determine whether it continues to meet the Federal 

Insecticide, Fungicide, and Rodenticide 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 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/. 

Amitraz is a formamidine insecticide/miticide, which is currently registered for use on 

cattle, swine, and canines to control various insects such as ticks, lice, and mange mites. 

The mode of action for amitraz is through a mechanism which causes an increase in 

nerve activity within arachnids; in addition, it also causes toxic effects through the 

octopamine receptor (which causes the insect/mite to release their bite (on host animals) 

before falling off the host animal and dying). There are two technical registrations and 

three end-use product registrations containing amitraz. 

Comments Received on Preliminary Work Plan

Comments were received from the Physicians Committee for Responsible Medicine 

(PCRM) regarding the amitraz Preliminary Work 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 timeline established in the PWP. In addition, 

through the PWP, EPA 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 topics. 
 

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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 ecological 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 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 Service (the Services), as appropriate. 

• The Agency anticipates needing the following data in order to conduct an 

endangered species and non-target ecological risk (and possibly drinking water) 

assessment for amitraz. 

o (GLN 835.1240) Absorption/desorption – degradates only 

o (GLN 850.2100) Avian oral toxicity – Passerine species 

o (GLN 850.4100) Terrestrial Plant toxicity Tier 1 seedling emergence 

o (GLN 850.4150) Terrestrial Plant toxicity Tier 1 vegetative vigor 

o (GLN 850.5400) Aquatic Plant Growth: algae 

• For more information regarding the status 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 Eligibility Decision (RED). The most recent 

non-comprehensive human health assessment (dietary and residential exposures 

only) for amitraz was completed in 2006 to support the Tolerance Reassessment 

Eligibility Decision (TRED) for amitraz. 

• Based upon the anticipated data requirements, the toxicological endpoints may be 

revised during the registration review of amitraz. 
 

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• The Agency anticipates conducting an occupational handler assessment but does 

not anticipate conducting a post-application occupational assessment during the 

registration review of amitraz (based on minimal worker interactions with treated 

animals in a professional environment). 

• The Agency anticipates conducting a new 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 plant and livestock tolerance expressions 

in 40 CFR §180.287 to clarify (i) that the 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 result in residential 

handler/applicator and post-application exposures. New toxicity studies may 

identify new endpoints for assessment and new residential exposure assessment 

SOPs are expected to be in place by the time the amitraz human health risk 

assessment is conducted. Therefore the Agency plans to conduct a revised 

residential handler and post-application risk assessment during the registration 

review of amitraz. 

• The Agency anticipates requiring the following 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-day) 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-day/28-day) Inhalation Toxicity 

o (GLN 870.3700) Pre-Natal Developmental Toxicities – Rabbit 

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

o (GLN 870.6200b) Neurotoxicity Battery (sub-chronic studies) 

o (GLN 870.6300) Developmental Neurotoxicity Study 

o (GLN 870.7800) Immunotoxicity 

• In response to a data call-in (DCI) from the amitraz TRED, the registrants have 

submitted draft protocols for a modified one-generation reproduction study (GLN 

870.3800) which includes pertinent measurements for developmental 

neurotoxicity and possible immunotoxicity parameters. If this study is 
 

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successfully completed, it may be used to satisfy data needs for neurotoxicity, 

reproduction and immunotoxicity studies. 

• For more information on the status and review 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-OPPTS-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 Registration 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 Received During Docket Opening

The amitraz registration review docket was 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 change 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 studies which were identified as data 

requirements in the Summary and Scoping documents. PCRM indicated that data 
 

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may already exist either with the technical registrants or other 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, refine and ultimately replace the use of 

animals for toxicity testing. As a result, the Agency is working with the technical 

registrants to develop a very efficient “extended one-generation reproduction 

protocol” which will greatly minimize replication 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: reproduction, immununotoxicity, neurotoxicity, 

developmental, clinical chemistry, hematology, urinalysis, oral toxicity, 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 obligations under FIFRA, FFDCA and FQPA. 

For detailed responses to comments received 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 (DCI) notice for the data gaps listed under the 

“Risk Assessment and Data Needs” section above. 

Both an ecological risk assessment, which will include an endangered species 

assessment, and a human health risk assessment will be conducted as detailed in the 

“Risk Assessment and Data Needs” section above.