Docket Number: EPA-HQ-OPP-2009-1015 

www.regulations.gov 

Amitraz Registration Review 

Summary Document: Initial Docket 

March 2010 

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TABLE OF CONTENTS 

 Page 

I. Preliminary Work Plan (PWP) 4 

II. Fact Sheet 10 

________________________________________________ 

Please Note 

This Preliminary Work Plan and Fact Sheet summarize the Environmental Protection Agency's 

current position on amitraz based on the following documents: 

1. Registration Review - Problem Formulation for Ecological Risk and Environmental Fate, 

Endangered Species, and Drinking Water Assessments for Amitraz (PC Code 106201). 

(DP Barcode: D367920, January 07, 2010). 

2. Updated Amitraz Human Health Assessment Scoping Document in Support of 

Registration Review. (DP Barcode: D367925, September 20, 2009). 

3. Food/Feed & Non-Food/Non-Feed Uses Considered in Registration Review Work 

Planning (April 07, 2009). 

4. Updated Review of Amitraz Incidents Reports (DP Barcode: D368729, November 24, 

2009) 
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I. Preliminary Work Plan 

Introduction:

The Food Quality Protection Act of 1996 (FQPA) mandated a registration review program. All 

pesticides distributed or sold in the United States (U.S.) generally must be registered by the 

Environmental Protection Agency (EPA or the Agency), 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 

amitraz. 

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. 

Anticipated Risk Assessment and Data Needs: 

 The Agency anticipates conducting comprehensive human health and ecological risk 

assessments including an endangered species assessment, for amitraz. 

Ecological Risk: 

• The most recent comprehensive ecological risk assessment was completed in January 

1994 to support the amitraz Reregistration Eligibility Decision (RED).

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

endangered species, non-target ecological risk and possible drinking water 

assessment for amitraz. 
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o (GLN 835.1240) Absorption/desorption - batch equilibrium for degradates 

only 

o (GLN 850.2100) Avian oral toxicity - Passerine species (Amitraz and 

degradates) 

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

(Amitraz and degradates) 

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

and degradates) 

o (GLN 850.5400) Aquatic Plant Growth: algae, Tier 1 (Amitraz and 

degradates) 

• The need for ecological data requirements for plant toxicity studies mentioned above is 

primarily based on uncertainties the Agency has with the lack of label directions for how 

to dispose of amitraz waste, which may lead to environmental exposures. The 

submission of use and disposal characterization may alleviate the need for some of data 

requirements. Please see the Guidance for Commenter’s Section for additional details on 

information needs. 

• 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, as appropriate. 

Amitraz degrades rapidly into several degradates. However, the two major degradates which 

the Agency will be considering during registration review are BTS 27271 and BTS 27919. 

• Please refer to the document: Registration Review - Problem Formulation for Ecological 

Risk and Environmental Fate, Endangered Species, and Drinking Water Assessments for 

Amitraz, available in the docket, for a more detailed discussion of the anticipated 

ecological risk assessment needs. 

Human Health Risk: 

• A comprehensive human health risk assessment was conducted to support the 1995 

Reregistration Eligibility Decision (RED) in December of 1994. In July of 2006, a 

human health risk assessment (for dietary and residential exposures) was conducted in 

support of the Tolerance Reassessment Eligibility Decision (TRED). 

• The Agency anticipates requiring the following studies, in accordance with the revised 

CFR 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 
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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 successfully completed, it may be used to 

satisfy data needs for neurotoxicity, reproduction and immunotoxicity studies. 

 

• Based upon the anticipated data, the Agency may revise the toxicological endpoints 

during the registration review of amitraz. 

• A new drinking water assessment may be conducted during registration review, which 

would include any updated hazard information. 

• 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. 

• 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 postapplication risk assessment during the registration review of amitraz. 

• Revisions to the residential risk assessment for amitraz would require a revised aggregate 

risk assessment to include food plus residential exposures. 

• The Agency anticipates conducting an occupational handler risk assessment during the 

registration review of amitraz, but does not anticipate conducting a post-application 

occupational assessment (based on minimal worker interactions with treated animals in a 

professional environment). 
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• Please refer to the document: Updated Amitraz Human Health Assessment Scoping 

Document in Support of Registration Review for a detailed discussion of the anticipated 

human health risk assessment needs.

Agricultural Health Study

Amitraz is among several agricultural chemicals included in the Agricultural Health Study 

(AHS). The AHS began in 1993 and is a collaboration of the National Institute of 

Environmental Health Sciences (NIEHS), the National Cancer Institute (NCI), the EPA, and the 

National Institute for Occupational Safety and Health (NIOSH). Designed as a large, long-term 

epidemiological study, the AHS collects and analyzes data on the health and work practices of 

nearly 90,000 farmers and their families in Iowa and North Carolina who enrolled in the study 

before any disease developed. The study focuses particularly on farmers' exposure to 50 

chemicals including many of the most widely used pesticides. As data are collected over a 

period of years, scientists can compare overall health outcomes for people who differ in whether 

they have had exposure to various chemicals. While these comparisons cannot conclusively 

demonstrate how exposure affects health, they can show some statistical associations. More 

information on the AHS can be found at: http://aghealth.nci.nih.gov. 

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 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. 

Amitraz is not among the group of 58 pesticide active ingredients 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 
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Review cases, including those for which EPA has already opened a Registration Review docket 

for a pesticide active ingredient. 

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 registration review of 

amitraz. 

Registration Review for Amitraz – Projected Registration Review Timeline 

Activities Estimated Date 

Phase 1: Opening the docket 

Open Public Comment Period for the Amitraz Docket 2010 – March 

Close Public Comment Period 2010 – May 

Phase 2: Case Development 

Develop Final Work Plan (FWP) 2010 – August 

Issue DCI 2011 – April - June 

Data Submission 2013 – April - June 

Open Public Comment Period for Preliminary Risk Assessments 2014 – Oct. – Dec. 

Close Public Comment Period 2015 – Jan. - March 

Phase 3: Registration Review Decision 

Open Public Comment Period for Proposed Reg. Review Decision 2015 – April - June 

Close Public Comment Period 2015 – July – Sept. 

Final Decision and Begin Post-Decision Follow-up 2016 

Total (years) 6 

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 for the amitraz 

case. 

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:
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Amitraz is 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 

http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=88

5. In addition, no Total Maximum Daily Loads (TMDL) have been developed for amitraz, based 

on information provided at 

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 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: 

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 many 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 amitraz, 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. 

One potential environmental justice issue particularly related to amitraz concerns the use of 

amitraz on dairy animals. Since milk is distributed in a relatively localized area, the Agency is 

looking into whether dairy animals in certain localities such as southern Texas and Puerto Rico 

are treated at a higher frequency than dairy animals in other parts of the country. During 

registration review, EPA is seeking information on high dairy treatment areas and milk 

distribution in order to determine if some subpopulations are disproportionately exposed to 

amitraz residues in milk. 

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: 

1. confirmation on the following label information 

a. sites of application 

b. maximum application rates 

c. frequency of application, application intervals, and maximum number of 

applications per year 

d. geographic limitations on use 
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2. use or potential use distribution (e.g., observed amounts applied to cattle and domestic 

canines) 

3. use history 

4. usage/use information for non-agricultural uses 

5. directly acquired county-level usage data (not derived from state level data) 

a. total pounds per year – county 

b. the year the pesticide was last used in the county/sub-county area 

c. the years in which the pesticide was applied in the county/sub-county area 

6. typical interval (days) 

7. state or local use restrictions 

8. ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian, insect 

(e.g., honey bees) and mammalian mortalities) not already reported to the Agency. 

9. monitoring data 

10. information regarding use on dairy animals including frequency and geographic 

distribution of use 

11. mass of amitraz per unit of volume of products 

12. estimates of how much chemical may wash off of livestock after treatment 

13. estimates of how much chemical overspray occurs during application to livestock. 

14. estimates of the maximum number of animals that may be treated at any given time 

15. practices of disposal for spent amitraz animal dips 

16. practices of disposal for rinsate from treating the walls and floors of swine houses. 

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 a Final Work Plan for the amitraz registration review 

case.
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II. FACT SHEET

 

Background Information:

• The registration review case number for amitraz is 0234. 

• The amitraz PC Code is 106201 and the CAS# is 33089-61-1. 

• The technical registrants are Arysta Lifescience America, Inc. and Fort Dodge Animal 

Health Division of Wyeth 

• Amitraz was first registered as an end-use product in 1975. 

• There are five active section 3 product registrations for amitraz: two technical products 

and three end-use products. 

• Amitraz belongs to the formamidine class of pesticides and is an alpha-adrenoceptor 

agonist insecticide/miticide registered for use on various species of ticks, lice and mites. 

• The Agency completed the amitraz RED in March 1995, and the TRED in July, 2006. 

• The Pesticide Re-evaluation Division Chemical Review Manager (CRM) is James 

Parker: parker.james@epa.gov. 

• Registration Division Product Manager (PM): Venus Eagle: eagle.venus@epa.gov. 

Use & Usage Information: 

• Amitraz is an insecticide/miticide registered for use on cattle, swine and canines to 

control various insects such as ticks (e.g., American Dog Tick, Spinose Ear Tick, and 

Black-legged Tick), lice (e.g., Biting and Sucking Lice), and mites (e.g., Scab and Mange 

Mites). 

• Amitraz is formulated as an emulsifiable concentrate, impregnated collar/tag, and a ready 

to use liquid. Furthermore, amitraz is applied via spray-dip machines, sprayers, low 

pressure ground sprayers, applicator tips, and by hand. 

Recent Actions:

• The Agency completed the product reregistration process for amitraz on June 16, 2008. 

Ecological Risk Assessment Status: 

The most recent ecological risk assessment for amitraz was completed in 1994 for the 1995 

RED. This risk assessment included the agricultural uses on cotton and pears and concluded that 

minimal exposure would occur from the livestock and pet uses. The agricultural uses of cotton 

and pears were cancelled in 2005 and only livestock and pet uses remain. A summary of amitraz 

risks from the cancelled uses in the 1994 assessment follows: 

Risks to Mammals 

• Amitraz use on pears and cotton posed chronic risk to nontarget mammalian species. 

Risks to Birds 

• Amitraz use on pears and cotton were found to pose potential chronic risk to nontarget 

avian species. No acute risks were seen from parent amitraz, but potential acute risks 

were noted from a major amitraz degradate (BTS-27271). 
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Risks to Aquatic Species 

• Amitraz use on cotton was not likely to cause acute or chronic risks to aquatic organisms 

because it dissipates rapidly in the environment. However, amitraz use on pears was 

found to produce chronic risks to aquatic organisms because it is used at higher 

application rates. Also, amitraz degradates BTS 27271 and BTS 27919 were found to be 

more persistent than the parent compound and thus likely to be acutely toxic to aquatic 

organisms. 

Risks to Non-Target Plants and Beneficial Insects 

• No guideline studies on non-target plants have been submitted; therefore risks to plants 

were not assessed in 1994.

• Amitraz was found to be practically nontoxic to beneficial insects (e.g., bees). Risk 

assessments were not conducted for beneficial insects in 1994. 

Please refer to the document: Registration Review - Problem Formulation for the Ecological 

Risk, Environmental Fate, Endangered Species, and Drinking Water Assessments for Amitraz in 

the registration review docket for more detailed information on any future ecological risk 

assessment for amitraz. 

Human Health Risk Assessment Status: 

Please refer to the document: Updated Amitraz Human Health Assessment Scoping Document in 

Support of Registration Review in the registration review docket for a detailed summary of the 

key findings of the most recent human health assessment. A summary follows: 

Hazard Characterization: 

• Two studies, an oral and a metabolism study conducted with human subjects, were 

considered together as the basis of the human health risk assessment conducted for the 

2006 TRED. 

• Based on the human metabolism study in two subjects, neurotoxic effects were seen in 

the central nervous system (CNS) of the two human subjects shortly after dosing, these 

effects disappeared within 12 hours. 

• In 2006, the amitraz carcinogenicity classification was re-evaluated and reclassified as 

“suggestive evidence of carcinogen” with no quantification required because the tumor 

data for amitraz was not perceived to be compelling by the Agency (e.g., no tumors 

identified in rats). 

Dietary (Food Only): 

• The acute dietary assessment conducted in support of the 2006 amitraz TRED did not 

include a drinking water or a chronic dietary assessment. The drinking water exposure 

assessment was not considered in the dietary risk assessment because in 2006 amitraz 

was not expected to enter water-bodies based on registered uses. No chronic dietary 

assessment was conducted because the Agency determined that the low endpoint from the 

acute assessment would be protective and because of rapid recovery, chronic exposure 

could be considered as a series of acute exposures. 

• Based upon the endpoint identified from the human study data and nationwide exposure 

estimates of 0.1% ai per head of cattle and swine and the tolerance revocation for hops, 
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all dietary risks were below the Agency’s level of concern for dietary exposures with the 

most highly exposed population at 28% of the aPAD.

Residential: 

• A residential assessment of the amitraz-impregnated pet collar use “Amitraz Revised 

Human Health Risk Assessment for the Tolerance Reassessment Eligibility Decision” 

was completed in support of the July 2006 amitraz TRED. 

• The amitraz residential assessment used to support the TRED in 2006 was based upon a 

carbaryl pet collar study which was later reclassified as supplemental (upgradable). A 

new carbaryl study has been submitted to refine the exposures from pet collars. That 

study is acceptable and shows lower exposures than were seen in the previous study. 

• No residential handler/applicator exposure scenarios were assessed in the 2006 TRED 

because the post-application residential assessment was deemed to be protective of all 

residential exposure scenarios (e.g., handler/applicator and post-application exposure). 

• Based on the 2.4 g ai pet collar use, all residential exposure scenarios, including toddler 

dermal and incidental oral (hand-to-mouth) exposures (MOE of 97), were not of concern 

to the Agency. 

Aggregate: 

• Generally, the Agency calculates aggregate risks consistent with potential exposure duration, 

including acute, short-term, intermediate-term and/or chronic. For acute aggregate risk, the 

Agency combines acute dietary food + water. For all other aggregate scenarios, the Agency 

combines chronic dietary with the appropriate residential exposure(s). 

• In the case of Amitraz, only acute dietary risks were estimated. Chronic dietary risks were 

not estimated due to a lack of appropriate endpoints. The Agency believes that the acute 

dietary risk is protective of the chronic dietary risk. The Agency estimated acute dietary risk 

at 28% of the aPAD for the highest exposed population subgroup.

• An atypical aggregate risk was estimated for amitraz which combined acute dietary 

exposures (food + water) with residential exposures resulting in an estimated MOE = 76. 

The Agency believes the estimated aggregate risk for amitraz to be conservative because 

aggregation of acute dietary exposure scenarios with short, intermediate, and/or long-term 

exposure scenarios is likely to over estimate potential exposures and risks. 

Occupational:

• Occupational handler exposures were anticipated by the Agency. However occupational 

handler risks have not been previously assessed because occupational handler exposures 

are anticipated to be considerably less than residential exposures/risks. 

• Occupational post-application Restricted Entry Intervals (REI’s) were required for the 

pear and cotton uses in the 1994 amitraz RED; however these uses have since been 

cancelled.

• The Agency has not assessed occupational exposures/risks from the treatment of cattle, 

swine and enclosed animal premises. 

Cumulative: 

• The Agency does not have data to determine whether amitraz shares a common mechanism 

of toxicity with other substances. As a result, the Agency has not made a common 
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mechanism of toxicity finding as to amitraz and any other substances, and amitraz does not 

appear to produce a toxic metabolite that is produced by other substances which have 

tolerances in the U.S. Therefore, EPA has not assumed that amitraz has a common 

mechanism of toxicity with other substances. 

Human studies

• For amitraz, humans are the most sensitive species tested with clinical signs similar to 

those observed in animals. 

• The three intentional exposure human toxicity studies listed below were reviewed by 

EPA in 2006 during the development of the amitraz human health risk assessment for 

tolerance reassessment: 

o Campbell J (1984). A Comparison of The Metabolism of (14c)-Amitraz in Rats, 

Mice, Baboon and Human. FBC Limited. MRID 160964. 

o Cass, L (1992) T-344, Amitraz: Report of A Double Blind Tolerance Study of 

Amitraz in Six Adult Healthy Volunteers: Lab Project. Number RD 197/20170. 

Unpublished study prepared by Simbec Research Ltd. MRID 43283101. 

o Langford, H. (1998) Amitraz (Code AE B049974): Human Volunteer DoubleBlind Dermal Tolerance Study: Lab Project Number: C00350: TOX 97228: RD 

197/21690. Unpublished study prepared by Simbec Research Ltd. MRID 

4463901. 

• OPP performed science and ethics reviews of these studies, applying the standards set 

forth in EPA’s Amended Rule for the Protection of Human Subjects of Research at 40 

CFR part 26. In addition, the studies were reviewed for scientific and ethical 

acceptability in April 2006 by the Human Studies Review Board (HSRB), as required for 

intentional exposure human studies reporting a toxic effect initiated before April 7, 2006 

and proposed for EPA reliance (40 CFR 26.1602(b)(2)). 

• The HSRB concluded that Campbell (1984) and Cass (1992), when considered together, 

were appropriate for establishing the point of departure for assessing acute dietary risk, 

but not appropriate for developing a point of departure for assessing chronic dietary risk, 

short-term oral exposure, or inhalation risk. The HSRB recommended against the use of 

Langford (1998) in the amitraz risk assessment due to significant scientific deficiencies in 

the study. 

• Consistent with the recommendations of the HSRB, EPA used Campbell (1984) and Cass 

(1992) to establish the point of departure for acute dietary risk assessment, and did not 

use Langford (1998) in the 2006 amitraz human health risk assessment. 
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• EPA will reconsider Campbell (1984) and Cass (1992) in the course of registration 

review, and will consider as well any other research involving intentional exposure of 

human subjects to amitraz brought to its attention. If EPA decides to rely on Campbell 

(1984) and/or Cass (1992) or any other human studies in future risk assessments, EPA 

will ensure that all applicable regulatory requirements are met. 

• In addition to the three human toxicity studies discussed above, EPA relied upon the 

following intentional exposure human study in 2006 for assessing the risks associated 

with the pet collar uses of amitraz: 

o Emlay, D.; Rudolph, R. (1977) Determination of the Quantity of Carbaryl 

Removed by Petting Dogs Wearing 16% Carbaryl Dog Collars: Lab Project 

Number: TR-506. Unpublished study prepared by Zoecon Industries, Inc. 14 p. 

{OPPTS 875.1500). Transferable Residues from Dogs Treated with 16% 

Carbaryl Collar (MRID 45792201). 

• The Agency performed an ethics review of the carbaryl pet collar study (MRID 

45792201), applying the standards in 40 CFR part 26 subpart Q, and concluded that the 

study was appropriate for EPA reliance. HSRB review was not required because the 

study does not report a toxic endpoint and was initiated before the effective date of 

EPA’s human studies rule. 

• Recently, however, EPA concluded that MRID 45792201 lacks appropriate quality 

assurance and quality control (QA/QC) procedures and adequate documentation for data 

generated in the laboratory and in the field, and that it is therefore not appropriate for use 

in EPA risk assessments. As a result, in registration review, the Agency plans to reassess 

the amitraz pet collar uses based on a different study which did not involve intentional 

human exposure, and will not rely on MRID 45792201 in future risk assessments. 

Incident Reports: 

• No ecological incidents in the EIIS database have been reported to the Agency for 

currently labeled uses of amitraz. 

• The Agency incident database has approximately 6000 reported domestic animal 

incidents with amitraz from the time period of 1992-2010. These reports include 

incidents on livestock and companion animals. The Agency will be conducting a 

thorough review of the domestic animal incident reports during registration review. 

• Five human incidents have been identified in the OPP Incident Data System (IDS) from 

2002 to present for amitraz. The Agency also consulted the Centers for Disease Control 

and Prevention/National Institute for Occupational Safety and Health (CDC/NIOSH) 

Sentinel Event Notification System for Occupational Risk (SENSOR) database and 

identified eight definite, probable or possible cases which involved amitraz incidents. 

Please refer to the document: Updated Review of Amitraz Incidents Reports for a detailed 

discussion of the anticipated human health risk assessment needs. 

Tolerances: 
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• U.S. Tolerances for amitraz are listed under 40CFR §180.287, and are expressed in terms 

of the combined residues of amitraz and its metabolites containing the 2, 4-

dimethylaniline moiety in or on the foods. Codex MRLs have also been established for 

amitraz in/on various commodities, and are currently expressed in terms of amitraz per 

se. Current incompatibility between U.S. tolerances of Codex levels exists due to 

tolerance differences in expression and analytical enforcement methods. 

 

• The tolerance expression in 40CFR §180.287 will be reviewed during registration review 

to ensure that it appropriately covers the metabolites and degrades of amitraz, and that it 

specifies the residues to be measured for each commodity. Any proposed revisions 

would be to the chemical description rather than the individual tolerance level(s). 

Data Call-In Status:

• Based on the 2008 amitraz reregistration Generic Data Call-In (GDCI), (GLN 870.3800) 

a modified Two Generation Reproduction and Fertility Effect study with reproduction 

and fertility effects data are due to be submitted to the Agency by April 23, 2012. UVVisibility Data from this 2008 DCI have been received. 

Labels: 

• Amitraz labels can be obtained from the Pesticide Label System (PPLS) website: 

http://oaspub.epa.gov/pestlabl/ppls.home. A summary of amitraz labels is provided in the 

table below. 

Amitraz Products 

Registration 

Number 

Product Name Active Ingredient 

2382-104 PREVENTIC TICK COLLAR FOR 

DOGS

9% 

54382-3 TAKTIC E.C. 12.5% 

80490-1 AMITRAZ SOLID 98% 

80490-2 PROMERIS SPOT ON FOR DOGS 14.34% 

85904-1 AMITRAZ INSECTICIDE 97%