Docket Number EPA-HQ-OPP-2011-0105 www.regulations.gov



## Amitrole Summary Document Registration Review: Initial Docket
June 20113 

### TABLE OF CONTENTS

I. Preliminary Work Plan (PWP) 4

II. Fact Sheet 12

III. Summary of Data Gaps 17

________________________ ______________________ ____________________

Please Note

This Preliminary Work Plan and Fact Sheet su mmarize the Environmental Protection Agency's current position based on the following documents:

1. Registration Review – Problem Formulation for the Ecological Risk and Drinking Water Exposure Assessments for Amitrole (P C Code 004401; DP Barcode D390513)

. M. Wagman. June 10, 2011.

2. Amitrole: Human Health Risk Scoping Do cument in Support of Registration Review . D. Drew. June 13, 2011.

3. BEAD Chemical Profile for Registration Review: Amitrole: PC Code 004401. K. RienzoStack. May 25, 2011.

4. Amitrole Use and Usage Information . August 19, 2010.

5. Amitrole Review of Human Incidents . K. Oo. March 1, 2011.

These and other supporting documents for the amitr ole registration review case may be found in the docket EPA-HQ-OPP-2011-0105 at http://www.regulations.gov.4 

### I. PRELIMINARY WORK PLAN – AMITROLE

Introduction :

The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program. All pesticides distributed or sold in the United Stat es (U.S.) generally must be registered by the Environmental Protection Agency (EPA or the Ag ency), based on scientific data showing that they will not cause unreasonable ri sks to human health or the environment when used as directed on product labeling. The registration review program is intended to ma ke 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 unreasonabl e 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 prog ram, the Agency periodically r eevaluates pesticides to make sure that as change occurs, products in the mark etplace can be used safely. Information on this program is provided at: http://www. epa.gov/oppsrrd1/registration_review/.

The Agency is implementing the registration revi ew program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), a nd will review each registered pesticide every 15 years to determine whether it continues to meet th e 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 belie ves are needed to make a registration review decision. After reviewing and responding to co mments and data received in the docket during this initial comment period, the Agency will de velop and commit to a final work plan and schedule for the registration review of amitrole.

Amitrole is a triazole-containing herbicide registered for use for outdoor general weed control to non-agricultural rights-of-way, industrial and construction sites, fencerows, and other

uncultivated areas. Tolerances are not curren tly established for amitrole as there are no registered food or feed uses. There are curren tly no residential uses for amitrole. One of amitrole’s degradates, cyanamide – a separate pesticide active ingredient, may be of toxicological concern because av ailable data indicate that cyan amide may be more toxic to aquatic organisms than the parent amitrole. Amitrole was first registered in 1948, and the Reregistration Eligibility Decision (RED) for Amitrole was completed in August 1996.

Anticipated Risk Assessment and Data Needs :

The Agency anticipates the need to require data and to conduct a comprehensive ecological risk assessment, including an endangered species a ssessment, for all uses of amitrole and its degradates of concern. For human health, EPA anticipates the need to require data and to conduct a dietary (drinking water only) assessment and revised occupational risk assessments during registration review. If t oxicological endpoints or points of departure are revised based on the data that are required for registration review, they will be considered in the new assessment, as well as any changes to the st andard operating procedures or default exposure assumptions. Below is a summary of the issues relevant to the registration review of amitrole.5 Ecological Risk:

• The most recent comprehensive ecological risk assessment for amitrole was completed in support of the 1996 Amitrole RED.

• An updated ecological risk assessment of a ll registered uses of amitrole and its degradates of concern will be conducted dur ing registration review. The new assessment will incorporate the most up-to-date modeling methodologies, updated toxicological endpoints, and data submitted under the antici pated registration review data call-in.

• A risk assessment that supports a complete endangered species determination has not been conducted for amitrole. The ecological risk assessment planned during registration review will allow the Agency to determin e whether amitrole’s use has “no effect” or “may affect” federally listed threatened or endangered species (listed species) or their designated critical habitats. When an asse ssment 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 Service and/or Nationa l Marine Fisheries Service (the Services), as appropriate.

• On January 19, 2011, the Center for Biologi cal Diversity and the Pesticide Action
Network North America filed a lawsuit in th e United States District Court for the Northern District of California, against th e Environmental Protection Agency (EPA) for allegedly failing to undergo consultation with the Services regarding the effects of over 350 pesticides, including amitrole, on ove r 200 endangered and threatened species throughout the United States (Center for Biologi cal Diversity, et al. v. EPA, et al., No. C 11-00293 (N.D.Cal.).

• Data gaps exist in the environmental fate and toxicity databases for amitrole. EPA is currently reviewing si x of the environmental fate st udies identified below. Although these studies have been submitted to EPA, they will be considered data gaps at this time until they have been reviewed and found to be acceptable. EPA anticipates requiring the following guideline studies for use in conducti ng a complete ecological risk assessment, including an endangered species assessment, for the regist ration review of amitrole.

Environmental Fate Guidelines:

835.1410 – Volatility, laboratory 835.2240 – Photodegradation in water 1
835.2410 – Photodegradation in soil 1

835.4100 – Aerobic soil metabolism 1

835.4200 – Anaerobic soil metabolism 835.4300 – Aerobic aquatic metabolism 1
835.4400 – Anaerobic aquatic metabolism 1

1 Data are currently in review for thes e studies. Although these studies have been submitted to EPA, they will be

considered data gaps at this time until the data have been reviewed and found to be acceptable.6 835.6100 – Terrestrial field dissipation 1
[If data currently in review are determined to be acceptable, only the Environmental chemistry analytical methods and independent laboratory validation (ILV) for soil portions of this guideline would be required.]

835.6200 2 – Environmental chemistry analytical methods and independent laboratory

validation for water 835.7100 – Ground water monitoring

Ecotoxicological Guidelines:

850.1350 – Aquatic invertebrate life cycle toxicity (saltwater, mysid shrimp, A. bahia) 850.1400 – Fish early life stage toxicity te st, TGAI (freshwater, rainbow trout) 850.1400 – Fish early life stage toxicity te st, TGAI (saltwater, sheepshead minnow) 850.2100 – Acute avian oral toxicity te st using a passerine species, TGAI 850.4100 – Seedling Emergence, Tier II, TEP 850.4150 – Vegetative Vi gor, Tier II, TEP

Ecotoxicological Guidelines with amitrole’s degradate, cyanamide:

850.1350 – Aquatic invertebrate life cycle toxicity (saltwater, mysid shrimp, A.
bahia ) 850.1400 – Fish early life stage toxicity test (freshwater, rainbow trout) 850.1400 – Fish early life stage toxicity test (saltwater, sheepshead minnow)

• One of amitrole’s degradates, cyanamide, itsel f is a plant growth regulator and pesticide active ingredient (PC Code 014002) currently undergoing regist ration review (Docket ID: EPA-HQ-OPP-2007-1014). Since cyanamide may be a major degradate of amitrole and the available data indicate that cyanamide ma y be more toxic to aquatic organisms than the parent amitrole, the three studies listed a bove are anticipated to be needed for use in conducting the planned registration revi ew risk assessment for amitrole.

The 2007 cyanamide problem formulation noted data gaps, but did not request data, for

chronic estuarine/marine fish and invertebrate tests. The problem formulation noted that

submission of these studies would reduce uncer tainty, and in the absence of these data, effects to salt water organisms would be a ssumed equivalent to effects on freshwater species. The more widespread nature of the amitrole use pattern, versus the limited use of cyanamide on fruit trees, makes it more likely that cyanamide exposure to estuarine organisms will occur as a result of amitrole use. Therefore, given the data gaps for cyanamide and their potential effects on the eco logical risk assessment for amitrole, EPA anticipates requiring a chronic estuarine/mari ne invertebrate and fish early life stage studies to be conducted with cyanamide as listed above.

2 See footnote 7 of 40 CFR 150.1300. EPA anticipates requiring only the environmental chemistry analytical

methods and ILV portions of this guideline for water.7 The freshwater fish early life stage st udy (MRID 44076701) cited in the 2007 cyanamide problem formulation is classifi ed as supplemental because effects were observed at all

test concentrations and a no observed effect concentration (NOEC) was not observed. A NOEC is needed for risk assessment purposes, an d therefore, these data are anticipated as being needed to reduce uncertainties in the risk assessment for amitrole

Lastly, seedling emergence and vegetative vigor studies for cyanamide were required in the cyanamide registration review data call-in (RR-014002-28861) issued on January 6, 2010. Due to the parent/degradate relationship between amitrole and cyanamide, these data may need to be considered during the registration review of amitrole.

• Please refer to the June 10, 2011 document Registration Review – Problem Formulation for the Ecological Risk and Drinking Wate r Exposure Assessments for Amitrole (PC Code 004401; DP Barcode D390513) in the amitrole registration review docket (EPAHQ-OPP-2011-0105) for a detailed discussion of the anticipated risk assessment and data

needs.

Human Health Risk:

• The most recent comprehensive human health risk assessment for amitrole was conducted in December 1995. Toxicological endpoints were revised in May 1996, and the changes were incorporated into the 1996 Amitrole RED.

• A dietary (food) exposure assessment is not anticipated as being needed during registration review because there are curren tly no registered food or feed uses for amitrole, and dietary (food) exposure is not expected based on registered uses.

• A drinking water dietary assessment for amitr ole has not previously been conducted, and EPA anticipates conducting one during registration review.

• Since there are no residential us es and no anticipated resident ial exposures from amitrole, residential handler and post-a pplication exposure assessments are not anticipated as being needed during registration review.

• Updates to the occupational handler expos ure assessments using current standard operating procedures and exposure assumptions are expected during registration review for currently registered amitrole products. It is anticipated that inhalation exposures will be assessed. However, a dermal exposure assessment is not an ticipated because the endpoint selected from the dermal developm ental toxicity study (1,500 mg/kg/day) is above the exposure expected based on the curr ently registered uses of amitrole. In addition to updating the three occupational handler scenarios asse ssed in the 1995 risk assessment, a handler assessment is expected to be performed duri ng registration review for mixing, loading, and applying water-dispersible granules. This scenario has not been previously assessed.

• Occupational post-applica tion inhalation exposures are expect ed to be negligible because re-entry is restricted until sprays have dr ied, and volatilization will be negligible. The8 dermal endpoint for an occupational post-ap plication dermal exposure assessment is above the exposure expected based on the curren tly registered uses of amitrole. For these reasons, occupational post-applic ation assessments for amitrole are not anticipated during registration review.

• EPA anticipates the need to require the following data for use in reevaluating and updating the human health toxicity profile for the registration review of amitrole:

870.1300 – Acute inhalation toxicity - rat 870.3465 – 90-day inhalation - rat

870.6200 – Acute and subchroni c neurotoxicity - rat 870.7800 – Immunotoxicity

• Please refer to the June 13, 2011 document Amitrole: Human Health Risk Scoping Document in Support of Registration Review in the amitrole registration review docket (EPA-HQ-OPP-2011-0105) for a detailed discussi on of the anticipated risk assessments

and data needs.

Endocrine Disruptor Screening Program :

As required by FIFRA and FFDCA, EPA reviews num erous studies to asse ss potential adverse outcomes from exposure to chemicals. Collectiv ely, these studies includ e acute, subchronic and chronic toxicity, including asse ssments of carcinogenicity, ne urotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influe nce, including effects on endocri ne target organ histopathology, organ weights, estrus cyclicity, sexual maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess gr owth, developmental and reprod uctive effects in different taxonomic groups. As part of its reregistration decision, EPA reviewed th ese data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA secti on 408(p), amitrole is subj ect to the endocrine screening part of the Endocrine Di sruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whet her 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 ot her such endocrine effect s as the Administrator may designate.” The EDSP employs a two-tiered approach to making th e statutorily required

determinations. Tier 1 consists of a battery of 11 scr eening 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 dose-response relationship between the dose and the E, A, or T effect.

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 679 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. Amitrole is not among the group of 58 pesticide active ingredients on the initial list to be screened under the EDSP. Accordingly, as part of registration review, EPA will issu e future EDSP orders/data callins, requiring the submission of EDSP screening assays for amitrole. For further information on the status of the EDSP, the policie s and procedures, the lis t of 67 chemicals, future lists, 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 timelin e for the completion of amitrole’s registration

review.

Registration Review for Amitrole – Pr ojected Registration Review Timeline

Activities Estimated Date Opening the Docket Open Docket and Public Co mment Period 2011 – June Close Public Comment 2011 – August Case Development

Final Work Plan 2011 – November Issue DCI 2012 – July – Sept. Data Submission 2014 – July – Sept. Open Public Comment Period for Draft Risk Assessments 2016 – Jan. – March Close Public Comment Period 2016 – April – June Registration Review Decision Open Public Comment Period for Proposed Registration Review

Decision 2016 – July – Sept.

Close Public Comment Period 2016 – Oct. – Dec. Registration Review Decision and Begin Post-Decision Follow-up 2017 Total (years) 6

Guidance for Commenters :

The public is invited to comment on EPA’s preliminary 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 fina l work plan for the amitrole 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 disparities between U.S. tolerances and MRLs in key export markets, providing as much specificity as possible regarding the na ture of the concern. Because amitrole is not registered for food/feed uses in the U.S., it has no U.S. tolerances. However, amitrole does have register ed food uses in other counties.10 Water Quality:

Amitrole is not identified as a cau se of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act 3 . In addition, no Total Maximum Daily Loads (TMDL) have been developed for amitrole 4 . More information on impaired water bodies and TMDLs can be found at the Agency’s website 5 . 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: Inclus ion of Impaired Water Body and Other Water Quality Data in OPP’s Registration Revi ew Risk Assessment and Management Process 6 in order to ensure they can be used quantitatively or qualitatively 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 any 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 amitrole 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 th e general population.

Other Information:

By a separate letter, EPA has asked the amitrole technical registrant, Nufarm Americas Inc., to provide additional information on several previously submitted environmental fate studies. This information is needed for use in conducting a full review of the submitted data.

Stakeholders are also specifically asked to prov ide information and data that will assist the Agency in refining the risk assessments, including any species-specific ecological determinations. The Agency is interested in obtaining the following information:

1. confirmation on the following label information

a. sites of application

b. formulations

c. application methods and equipment

d. maximum application rates

e. frequency of application, applicati on intervals, and maximum number of applications per season

f. geographic limitations on use

2. use or potential use distribution ( e.g. , acreage and geographical di stribution of relevant use sites)

3 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885

4 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl _pollutant_detail?p_pollutant_group_id=885&p_pollutant_

group_name=PESTICIDES

5 http://www.epa.gov/owow/tmdl/

6 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm11 3. use history

4. median and 90 th percentile reported use rates (lbs ai/1000 sq ft) from usage data – national, state, and county

5. application timing (date of firs t application and application in tervals) – national, state, and county

6. sub-county use site location data

7. usage/use information for non-agricultural uses

8. directly acquired county-level usage da ta (not derived from state level data)

a. maximum reported use rate (lbs a i/acre) from usage data – county

b. median and 90 th percentile number of applications – county

c. total pounds per year – county

d. the year the pesticide was last us ed in the county/sub-county area

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

9. typical application interval (days)

10. state or local use restrictions

11. ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian and mammalian mortalities) not alr eady reported to the Agency

12. monitoring data

Next Steps :

After the 60-day public comment period closes , the Agency will review and respond to any comments received in a timely manner and then i ssue a Final Work Plan for the registration

review of amitrole.12 

### II. FACT SHEET

Background Information :

• Amitrole registration review case number: 0095.

• Amitrole PC code: 004401.

• Amitrole CAS No.: 61-82-5.

• Amitrole was first registered for us e in the United States in 1948.

• The Amitrole RED was completed in August 1996.

• The technical registrant for amitr ole is Nufarm Americas, Inc.

• There are currently two end- use products and one technical product registered for amitrole. There are no active state-specifi c Special Local Need registrations or emergency exemptions.

• As a result of the product reregistration pr ocess following the Amitrole RED, one product was cancelled in 1997 and two were reregistered in 2006.

• Because there are no food or feed uses of amitr ole, there are no tolerances established for

this chemical.

• Pesticide Re-evaluation Di vision, Chemical Review Manager: Monica Wait, wait.monica@epa.gov

• Registration Division, Product Mana ger: Kable (Bo) Davis, davis.kable@epa.gov

Use & Usage Information : (For additional details on label rates and use sites, refer to Amitrole Use and Usage Information, August 19, 2010 and the BEAD Chemical Profile for Registration Review: Amitrole, May 25, 2011, in the amitrole registrati on review docket EPA-HQ-OPP2011-0105.)

• Amitrole is an herbicide registered for us e outdoors for general weed control to nonagricultural rights-of-way, i ndustrial and construction site s, fencerows, and other uncultivated areas. Amitrole is registered for use along highways, railroads, public utilities, and industrial areas and may be us ed to keep these areas vegetation free for maximum visibility, safety, and to prevent th e growth of potentially combustible weeds.

• There are no registered food or feed uses of amitrole, and there are no residential or
homeowner uses.

• Amitrole end-use products are formulated as a water-dispersible granule and in water soluble bags (formulation t ype not specified on label).

• Amitrole is applied by fixed-boom sprayers at tached to tractors, trucks, or railroad

wagons.

• Amitrole was previously classified as a “restr icted use” pesticide, but that classification was rescinded following incorporation of mitigation measures, use cancellations, and product cancellations specifi ed by the Amitrole RED.13 • EPA does not have a current nationwide esti mate of amitrole usage. Data from the California Department of Pesticide Regulat ion indicated that le ss than 10 pounds were applied per year from 2006 to 2008 for the state of California only.

• Although dated, the 1996 Amitrole RED estimated that national usage of amitrole was at or below 40,000 to 60,000 pounds of active ingredient per year.

Ecological Risk Assessment Status :

Please refer to the Registration Review – Problem Form ulation for the Ecological Risk and Drinking Water Exposure Assessments for Am itrole (PC Code 004401; DP Barcode D390513)

, June 10, 2011 for a detailed discussion of the key findings of the most recent ecological risk assessments. A summary follows:

Summary of Risks:

• The most recent comprehensive ecological risk assessment for amitrole was completed in support of the 1996 Amitrole RED.

• The ecological risk assessment conducted in support of the RED concluded that maximum labeled use rates of amitrole for regi stered uses at that time exceeded acute endangered species levels of c oncern (LOCs) for birds feedin g on short and tall grass and broadleaf plants and for small mammals consum ing short grass and insects. Since there was no mortality at the highest concentration in the avia n dietary test, amitrole was considered to represent low acute risk to birds.

• The RED concluded that no acute LOCs we re exceeded for freshwater fish or invertebrates, but risk to estuarine/marine invertebrates exceeded the acute endangered species LOC of 0.05.

• Chronic risk to mammals exceeded the ch ronic LOC of 1.0 for small herbivores consuming short grass, seeds and insects, whil e chronic risk to bird s, fish and aquatic

invertebrates was not assesse d due to a lack of data.

Human Health Risk Assessment Status :

Please refer to Amitrole: Human Health Ri sk Scoping Document in Support of Registration

Review

, June 13, 2011 for a detailed discussion of the key findings of the most recent human health risk assessment. A summary follows:

Hazard Characterization :

• The primary target organ is the thyroid. Data from short-term and chronic studies indicate that effects will appear in the thyroi d at lower dose levels than any other target

organ.14 • Amitrole was previously classified as a probable human carcinogen by the Office of Pesticide Programs (OPP) Carcinogenicity P eer Review Committee. This carcinogen classification was based on thyroid tumors in both sexes of multiple strains of rats, pituitary tumors in rats, and liver tumors in two strains of mice. In 2006, OPP’s Cancer Assessment Review Committee (CARC) re-eva luated the carcinogenic potential of

amitrole and reclassified amitrole as “ Not Likely To Be Carcinogenic To Humans At Doses That Do Not Alter Rat Thyroid Hormone Homeostasis. ” (See the Amitrole: Human Health Risk Scoping Document in Support of Registration Review for further details.)

• Based on the overall weight of the evidence fo und in the genotoxicity database, amitrole is not considered to be a mutagen or to cause thyroid follicular cell carcinogenesis through a mutagenic mode of action.

Dietary (Food and Drinking Water) :

• A dietary exposure assessment was no t conducted during the 1995 amitrole risk assessment because amitrole had no registered food uses.

• A drinking water assessment for amitrol e has not previously been conducted.

Residential (Non-occupational):

• All homeowner products were voluntarily cance lled following the 1984 Notice of Special Review for amitrole. Therefore, reside ntial handler and post-application exposure assessments were not required or co nducted for the 1995 risk assessment.

Aggregate:

• An aggregate risk assessment typically ev aluates the combined risk from dietary exposure (food plus drinking water) and any re sidential uses. However, since there were no residential or dietary e xposures for amitrole, an aggregate assessment was not conducted during the most recent assessment

• Amitrole is a triazole-derived herbicide. A triazole-metabolite aggregate assessment has been completed for the triazole class of chemicals. Amitrole has not been included in this assessment, because it is not expected to fo rm the free triazole, triazole-alanine, or

triazole acetic acid meta bolites. Furthermore, the toxicity profile of amitrole is distinct from the triazole metabolites, producing primaril y thyroid hyperplasia in chronic studies. Conversely, the triazole metabolites produce ne urotoxicity, developmental toxicity, blood cell toxicity, and skeletal deformations.

Occupational Handlers:

• The 1995 occupational handler risk assessment i ndicated that the margins of exposure for

short- and intermediate-term inhalation exposures at baselin e protection (i.e., no15 respirator) were not of concern to the Agen cy. Because the endpoint selected from the dermal developmental toxicity study (1,500 mg/k g/day) was above the exposure expected based on the registered uses of amitrole, a dermal exposure assessm ent was not required or conducted as part of the 1995 risk assessment.

Occupational Post-application:

• A quantitative occupational post-applica tion assessment was not conducted during the
1995 risk assessment. Amitrole is used in ar eas, such as rights-of-w ay, industrial areas, and other non-crop areas, where frequent or routine entry by persons who may contact treated surfaces is unlikely. EPA determined that such post-applic ation exposures do not appear to pose an unreasonable risk to pers ons entering treated areas, as long as entry is not permitted immediately after application. To prevent immediate re-entry, the current labels specify, “Do not enter or allow employees to enter treated areas until sprays have

dried.”

Reliance on Human Studies:

• Past amitrole risk assessments rely in part on data from studies in which adult human subjects were intentionally exposed to a pesticide to determine their dermal and inhalation exposure. Many such studies, invo lving exposure to many different pesticides, comprise generic pesticide exposure database s such as the Pestic ide Handlers Exposure Database (PHED) and the Agricultural Reen try Task Force (ARTF) Database. EPA has reviewed all the studies supporting these multi- pesticide generic exposure databases, and has found no clear and convincing evidence that the conduct of any of them was either fundamentally unethical or significantly deficient relativ e to the ethical standards prevailing at the time the research was conducte d. All applicable re quirements of EPA’s

Rule for the Protection of Hu man Subjects of Research ( 40 CFR Part 26) have been satisfied, and there is no re gulatory barrier to continue d reliance on these studies.

Cumulative:

• For the purposes of this registration review , EPA has not assumed nor determined that amitrole has a common mechanism of toxicity with other substances. For information regarding EPA’s efforts to determine whic h chemicals have a common mechanism of toxicity and to evaluate the cumulative e ffects of such chemicals, see the policy statements released by EPA’s Office of Pesticide Programs concerning common mechanism determinations and procedures fo r cumulating effects from substances found

to have a common mechanism on EPA’s website at: http://www.epa.gov/pesticides/cumulative/ . If, in the future, the Agency determines that

new information on amitrole is available that could potentially impact a cumulative risk assessment and result in a risk of concern, the Agency will revisit the need for a

cumulative risk assessment.16 Incidents :

• EPA’s preliminary review of the Ecological Incident Information System (EIIS, version 2.1) and the Avian Monitoring Information System (AIMS) on April 19, 2011, indicated that no “major” fish, wildlife, or plant incide nts associated with the use of amitrole have been reported to the Agency. Additionall y, no incidents involvi ng amitrole have been reported to the Agency in aggregated inci dent reports which are intended to capture “minor” fish, wildlife, and plant incidents. However, for various reasons, such as decreased monitoring and sublethal effects wh ich are not easily observed, the absence of reported incidents should not be constr ued as the absen ce of incidents.

• A summary report listing human incidents for amitrole has been provided in the docket

item entitled Amitrole Review of Human Incidents , March 1, 2011. The evaluation of the OPP Incident Data System (IDS) indicated no incidents identified in the United States from 2002 thru 2010 for the single chemical amitrole. In Aggregate IDS, from 2002 to February 2011, there are five cases reported for amitrole. Aggregate IDS only includes counts of incidents classified as “minor,” “unknown,” or “no effects,” and no additional details about the incidents are provided. For amitrole, the low frequency and severity of incident cases suggests a low potential for exposure to this chemical. There does not appear to be a concern at this time that would warrant further investigation.

Tolerances and International Harmonization :

• Because there are no registered food or feed us es for amitrole, no tole rances are currently

established.

Data Call-In Status :

• A generic data call-in (GDCI-004401-17739) was issued in December 1996 as a result of the data requirements listed in the 1996 Am itrole RED. All of the data requirements

from the RED data call-in have been fulfilled or waived.

Labels :

• A list of registration numbers for the amitrole case is provided below, and the labels can

be obtained from the Pesticide Pr oduct Label System (PPLS) website 7

.

Registration
# Registration Name Company Name % Active Ingredient

33688-5 Technical Amitrole Nufarm SA 92.7

33688-6 Maxata Branch Industrial Herbicide Nufarm SA 88.2

33688-10 Maxata Water Soluble Granules Nufarm SA 86.2

7 http://oaspub.epa.gov/pestlabl/ppls.home17 

### III. SUMMARY OF DATA GAPS – AMITROLE

The table below summarizes all anticipated data n eeds for amitrole in Section I, of this document ( Preliminary Work Plan ), the Registration Review – Problem Formulation for the Ecological Risk and Drinking Water Exposure Assessments for Amitrole (PC Code 004401; DP Barcode D390513) dated June 10, 2011, and the Amitrole: Human Health Risk Scoping Document in Support of Registration Review dated June 13, 2011.

Guideline

Number Anticipated Data Need Test

Material Estimated

Timeframe

(Months from receipt of DCI)

835.1410 Volatility, laboratory TEP 12 835.2240 Photodegradation in water 8 TGAI 12

835.2410 Photodegradation in soil 8 TGAI 12

835.4100 Aerobic soil metabolism 8 TGAI 24

835.4200 Anaerobic soil metabolism TGAI 24 835.4300 Aerobic aquatic metabolism 8 TGAI 24 835.4400 Anaerobic aquatic metabolism 8 TGAI 24 835.6100 Terrestrial field dissipation 8, 9 TEP 24

835.6200 Environmental chemistry analytical methods and independent laboratory validation (ILV) for

water 10 TGAI 12

835.7100 Ground water monitoring TEP 12

850.1350 Aquatic invertebrate lifecycle (saltwater, mysid shrimp, A. bahia) TGAI 12

850.1350 Aquatic invertebrate lifecycle (saltwater mysid shrimp, A. bahia) for the degradate cyanamide TGAI 12

850.1400 Fish early life stage toxicity test (freshwater, rainbow trout) TGAI 12

850.1400 Fish early life stage toxicity test (freshwater, rainbow trout) for the degradate cyanamide TGAI 12

850.1400 Fish early life stage toxicity test (saltwater, sheepshead minnow) TGAI 12

850.1400 Fish early life stage toxicity test (saltwater, sheepshead minnow) for the degradate cyanamide TGAI 12

850.2100 Avian oral acute toxicity test using a passerine species TGAI 12 850.4100 Seedling Emergence, Tier II TEP 12

8 Data are currently in review for thes e studies. Although these studies have been submitted to EPA, they will be

considered data gaps at this time until the data have been reviewed and found to be acceptable.

9 If data currently in review are determined to be acceptable, only the Environmental chemistry analytical methods

and ILV for soil portions of this guideline would be required.

10 See footnote 7 of 40 CFR 150.1300. EPA anticipates requiring only the environmental chemistry analytical

methods and ILV portions of this guideline for water.18 Guideline

Number Anticipated Data Need Test

Material Estimated

Timeframe

(Months from receipt of DCI)

850.4150 Vegetative Vigor, Tier II TEP 12 870.1300 Acute inhalation toxicity - rat TGAI 8 870.3465 90-day inhalation - rat 11 TGAI 24 870.6200 Acute and subchronic neurotoxicity - rat TGAI 24 870.7800 Immunotoxicity Study TGAI 12

11 The timeframe for this study may be able to be reduced from 90 days to 28 days if the data plateaus during the

test, or if exposure potential is not expected to exceed 28 days.