Docket Number: EPA-HQ-OPP-2009-1015 www.regulations.gov



## Amitraz Registration Review Summary Document: Initial Docket
March 20103 

### TABLE OF CONTENTS

Page

I. Preliminary Work Plan (PWP) 4

II. Fact Sheet 10

________________________ ________________________

Please Note

This Preliminary Work Plan and Fact Sheet su mmarize 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 Ba rcode: D367925, September 20, 2009).

3. Food/Feed & Non-Food/Non-Feed Uses C onsidered in Registration Review Work Planning (April 07, 2009).

4. Updated Review of Amitraz Incidents Reports (DP Barcode: D368729, November 24, 2009)4 

### I. Preliminary Work Plan

Introduction: The Food Quality Protection Act of 1996 (FQP A) 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 re quired 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, wh ich is currently registered for use on cattle, swine, and canines to control vari ous insects such as ticks, lice, and mange mites. The mode of action for amitraz is through a mechanism which cau ses an increase in ne rve activity within arachnids; in addition, it also cau ses toxic effects through the oct opamine receptor (which causes the insect/mite to release their bite (on host an imals) before falling off the host animal and dying). There are two technical registrations a nd three end-use product re gistrations containing
amitraz.

Anticipated Risk Assessment and Data Needs: The Agency anticipates conducting comprehe nsive human health and ecological risk assessments including an endangered species assessment, for amitraz.

Ecological Risk:

• The most recent comprehensive ecological ri sk assessment was completed in January 1994 to support the amitraz Reregistra tion Eligibility Decision (RED).

• The Agency anticipates needing the fo llowing data in order to conduct an endangered species, non-target ecologi cal risk and possi ble drinking water
assessment for amitraz.5 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 toxi city, 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 th e 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 characterizati on 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 asse ssment that supports a complete endangered species determination. The ecological risk a ssessment 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 e ndangered species (listed species) or their designated critical habitats. When an assessm ent concludes that a pesticide’s use “may affect” a listed species or its designated critic al habitat, the Agency will consult with the
U.S. Fish and Wildlife Se rvice, as appropriate.

Amitraz degrades rapidly into several degradates. However, the two major degradates which the Agency will be considerin g during registration review ar e BTS 27271 and BTS 27919.

• Please refer to the document: Registration Review - Problem Formulation for Ecological Risk and Environmental Fate, Endangered Spe cies, and Drinking Wate r 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 a ssessment 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 followi ng 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-da y) Oral Toxicity Study in Rats

o (GLN 870.3150) Sub-chronic (90-day) Oral Toxicity Study in Dogs6 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 Deve lopmental Toxicities – Rabbit

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

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

o (GLN 870.6300) Developmen tal Neurotoxicity Study

o (GLN 870.7800) Immunotoxicity

• In response to a data call-in (DCI) from th e amitraz TRED, the registrants have submitted draft protocols for a modified one-gen eration reproduction study GLN 870.3800 which includes pertinent measurements for deve lopmental neurotoxicity and possible immunotoxicity parameters. If this study is successfully completed, it may be used to satisfy data needs for neurotoxicity, re production 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 c onducted 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 to lerance covers metabolites and degradates of amitraz and (ii) that compliance with the specified tolera nce levels is to be determined by measuring only the specific compounds mentioned in th e tolerance expression to reflect current methodology and policy.

• Use of dog collars impregnated with amitraz is anticipated to re sult in residential handler/applicator and post-application expos ures. New toxicity studies may identify new endpoints for assessment and new re sidential exposure assessment SOPs are expected to be in place by the time th e amitraz human health risk assessment is conducted. Therefore the Agency plans to condu ct a revised resident ial handler and postapplication risk assessment during the re gistration review of amitraz.

• Revisions to the residential ri sk assessment for amitraz would require a revised aggregate
risk assessment to include f ood plus residential exposures.

• The Agency anticipates conducting an occupa tional handler risk assessment during the registration review of amitraz, but does not anticipate conducti ng a post-application occupational assessment (based on minimal worker interactions with treated animals in a professional environment).7 • Please refer to the document: Updated Amitraz Human He alth 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 chemical s 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 Nati onal Cancer Institute (NCI), the EPA, and the National Institute for Occupational Safety and Hea lth (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 focu ses particularly on fa rmers' 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 he alth 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 ca n show some statistical associations. More
information on the AHS can be found at: http://aghea lth.nci.nih.gov

.

Endocrine Disruptor Screening Program:

As required under FFDCA section 408(p), EP A has developed the Endocrine Disruptor Screening Program (EDSP) to determine whether certain substances (inc luding pesticide active and other ingredients) may have an effect in humans or wildlife si milar 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 ap proach 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 estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine related eff ects caused by the substance, and establish a quantitative relationship betw een 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 pesticid e active ingredients and 9 inert ingredients.
This list of chemicals was selected based on th e potential for human exposure through pathways such as food and water, residen tial activity, and certain post-applic ation agricultural scenarios.
This list should not be construed as a lis t of known or likely endocrine disruptors.

Amitraz is not among the group of 58 pesticide active i ngredients on the initial list to be screened under the EDSP. Under FFDCA sec. 408(p) the Agen cy must screen all pesticide chemicals. Accordingly, EPA anticipates issuing future EDSP orders/data call-ins for all Registration8 Review cases, including those for which EPA ha s already opened a Registration Review docket for a pesticide active ingredient.

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, pl ease visit our website: http://www.epa.gov/endo/

.

Timeline: EPA has created the following estimated timeline fo r the completion of the registration review of
amitraz.

Registration Review for Amitraz – Proj ected 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 comme nt on EPA’s preliminary regist ration review work plan and rationale. The Agency will carefully consid er all comments as well as any additional information or data provided in a timely manner pr ior to issuing a final work plan for the amitraz

case.

Trade Irritants: Through the registration review process, the Ag ency intends to solicit information on trade irritants and, to the extent feas ible, take steps toward facilitating irritant resolution. Growers and other stakeholders are asked to comment on any tr ade irritant issues resulting from lack of Maximum Residue Limits (MRLs) or disparitie s between U.S. tolerances and MRLs in key export markets, providing as much specificity as possible regarding the nature of the concern.

Water Quality:9 Amitraz is not identified as a cause of impairme nt for any water bodies listed as impaired under section 303(d) of the Clean Water Ac t, 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 (T MDL) have been developed for amitraz, based on information provided at http://iaspub.epa.gov/tmdl_waters10/attains_ nation.tmdl_pollutant_de tail?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 exte nt possible, data should conform to the quality standards in Appendix A of the OPP Standard Operating Procedur e: Inclusion of Impaired Water Body and Other Water Quality Data in OPP’s Regist ration Review Risk Assessment and Management Process (see: http://www.epa.gov/oppsrrd1/regist ration_review/water_quality_sop.htm ) in order to ensure they can be used quantitatively or qualitati vely in pesticide risk assessments.

Environmental Justice:
EPA seeks to achieve environmenta l justice, the fair tr eatment and meaningful involvement of all people, regardless of race, color, national origi n, or income, in the deve lopment, implementation, and enforcement of environmental laws, regulati ons, 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 thei r location, cultural practices, or other factors, may have atypical, unusually high exposure to amitraz, compared to the gene ral population. Please comment if you are aware of any sub-populatio ns that may have atypical, unusually high exposure compared to the general population.

One potential environmental just ice 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 anim als in other parts of the country. During registration review, EPA is seeking informa tion on high dairy treatment areas and milk
distribution in order to determine if some subpopulations are dispropor tionately exposed to
amitraz residues in milk.

Other Information: Stakeholders are also specifically asked to prov ide information and data that will assist the Agency in refining the risk assessments, incl uding 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, applicati on intervals, and maximum number of applications per year
d. geographic limitations on use10 2. use or potential use distribu tion (e.g., observed amounts appl ied to cattle and domestic canines)
3. use history
4. usage/use information for non-agricultural uses
5. directly acquired county-level usage da ta (not derived from state level data)

a. total pounds per year – county
b. the year the pesticide was last us ed 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 anim als including frequency and geographic
distribution of use
11. mass of amitraz per unit of volume of products
12. estimates of how much chemical may wa sh 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 ri nsate from treating the walls and floors of swine houses.

Next Steps: After the 60-day comment period closes, the Ag ency will review and respond to any comments received in a timely manner, and then issue a Fi nal Work Plan for the amitraz registration review

case.11 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 regi strations 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 regi stered 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 (P M): Venus Eagle: eagle.venus@epa.gov.

Use & Usage Information:

• Amitraz is an insecticide/miticide register ed 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 Suck ing Lice), and mites (e.g., Scab and Mange Mites).

• Amitraz is formulated as an emulsifiable c oncentrate, impregnated collar/tag, and a ready to use liquid. Furthermore, amitraz is a pplied via spray-dip machines, sprayers, low pressure ground sprayers, a pplicator tips, and by hand.

Recent Actions:

• The Agency completed the product reregi stration 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 agricultu ral 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 an d 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 chroni c 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).12 Risks to Aquatic Species

• Amitraz use on cotton was not likely to cause ac ute 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 BT S 27919 were found to be more persistent than the pare nt 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 practica lly nontoxic to beneficial insects (e.g., bees). Risk
assessments were not conducted fo r 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 detail ed information on any future ecological risk
assessment for amitraz.

Human Health Risk Assessment Status:
Please refer to the document: Updated Amitraz Human Health Assess ment 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 st udy conducted with human subjects, were considered together as the ba sis of the human health risk assessment conducted for the
2006 TRED.

• Based on the human metabolism study in two su bjects, neurotoxic eff ects were seen in the central nervous system (CNS) of the tw o human subjects shor tly after dosing, these effects disappeared within 12 hours.

• In 2006, the amitraz carcinogenicity classificatio n was re-evaluated and reclassified as “suggestive evidence of carcinogen” with no quantification require d 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 base d on registered uses. No chronic dietary assessment was conducted because the Agency de termined that the low endpoint from the acute assessment would be protective and b ecause of rapid recovery, chronic exposure
could be considered as a se ries 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 a nd swine and the tolera nce revocation for hops,13 all dietary risks were below the Agency’s leve l of concern for dietar y exposures with the most highly exposed populat ion at 28% of the aPAD.

Residential:

• A residential assessment of the amitraz-im pregnated 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 wa s later reclassified as supp lemental (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 exposur e 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 expos ures 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 antici pated by the Agency. However occupational handler risks have not been previously asse ssed because occupati onal handler exposures are anticipated to be considerably le ss than residential exposures/risks.

• Occupational post-application Restricted Entr y Intervals (REI’s) were required for the pear and cotton uses in the 1994 amitraz RE D; however these uses have since been
cancelled.

• The Agency has not assessed occupational expo sures/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 common14 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 spec ies tested with clinical signs similar to
those observed in animals.

• The three intentional exposure human toxicity studies listed belo w 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 Me tabolism 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 Pr oject 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, appl ying the standards set
forth in EPA’s Amended Rule for the Protec tion of Human Subjects of Research at 40 CFR part 26. In addition, the studies we re reviewed for scientific and ethical acceptability in April 2006 by the Human Studi es 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) a nd Cass (1992), when considered together, were appropriate for establis hing the point of departure fo r assessing acute dietary risk,
but not appropriate for developing a point of de parture 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 scientif ic deficiencies in the study.

• Consistent with the recommendations of the HSRB, EPA used Campbell (1984) and Cass (1992) to establish the point of departure fo r acute dietary risk assessment, and did not use Langford (1998) in the 2006 amitr az human health risk assessment.15 • EPA will reconsider Campbell (1984) and Ca ss (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) Determina tion 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. HS RB 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 th erefore not appropriate for use in EPA risk assessments. As a result, in re gistration review, the Agency plans to reassess the amitraz pet collar uses based on a differe nt 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 appr oximately 6000 reported domestic animal incidents with amitraz from the time pe riod of 1992-2010. These reports include incidents on livestock and companion animals. The Agency will be conducting a thorough review of the domestic animal in cident 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 Occ upational Safety and Health (CDC/NIOSH) Sentinel Event Notification System for O ccupational Risk (SENSOR) database and identified eight definite, pr obable 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:16 • U.S. Tolerances for amitraz are listed unde r 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. to lerances 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 me tabolites and degrades of amitraz, and that it specifies the residues to be measured fo r each commodity. Any proposed revisions
would be to the chemical de scription rather than the i ndividual tolerance level(s).

Data Call-In Status:

• Based on the 2008 amitraz reregistration Gene ric Data Call-In (GDCI), (GLN 870.3800) a modified Two Generation Reproduction a nd 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 la bels 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%