Docket Number EPA-HQ-OPP-2011-0105 

www.regulations.gov 

Amitrole Final Work Plan 

Registration Review 

December 2011 

 

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FINAL WORK PLAN – AMITROLE 

Introduction: 

This is the Environmental Protection Agency’s (EPA or the Agency) Final Work Plan (FWP) for 

the registration review of amitrole. The FWP includes the expected registration review timeline. 

The FWP also addresses any public comments received on the Preliminary Work Plan (PWP) in 

the Summary Document, which was posted in the amitrole registration review docket (EPA-HQOPP-2011-0105). The Summary Document, dated June 16, 2011, provided information on what 

EPA knows about the pesticide and what additional risk analyses and data or information the 

Agency believes are needed to make a registration review decision. 

The Agency’s implementation of the registration review program requires review of each 

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

Insecticide, Fungicide, and Rodenticide Act (FIFRA) standard for registration. Changes in 

science, public policy, and pesticide use practices occur over time. The registration review 

program is intended to make sure that, as the ability to assess risk evolves and as policies and 

practices change, all registered pesticides continue to meet that statutory standard. The public 

phase of registration review begins when the initial docket is opened for each case. Information 

on this program is provided on the Agency’s website1

. 

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 currently established for amitrole as there are no 

registered food or feed uses. There are currently no residential uses for amitrole. One of 

amitrole’s degradates, cyanamide – a separate pesticide active ingredient – may be of 

toxicological concern because available data indicate that cyanamide 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. 

Updates Since the Summary Document was Issued:

In letters dated August 16, August 31, and September 9, 2011, Nufarm Americas Inc., the 

technical registrant for amitrole, responded to EPA’s June 16, 2011 letter and provided 

additional details regarding previously submitted environmental fate studies [Guidelines (GLN) 

835.4100, aerobic soil metabolism; 835.4300, aerobic aquatic metabolism, and 835.6100, 

terrestrial field dissipation studies]. 

The June 10, 2011 document Registration Review – Problem Formulation for the Ecological 

Risk and Drinking Water Exposure Assessments for Amitrole was revised on December 7, 2011 

to incorporate the following changes to the environmental fate data requirements: 

 The Agency has completed its review of two environmental fate studies which were 

noted as “in review” in the June 2011 Summary Document. Reviews of GLNs 835.4100, 

 

1

 http://www.epa.gov/oppsrrd1/registration_review/ 
4

aerobic soil metabolism and 835.4300, aerobic aquatic metabolism classified the studies 

as “supplemental” and useful for risk assessment purposes. For that reason they have 

been removed from the list of data needs in this document. 

 Review of GLN 835.6100, terrestrial field dissipation, which was also noted as “in 

review” in the Summary Document, is not yet complete. EPA expects to finish its review 

of that study in early 2012, prior to issuance of the data call-in (DCI). Once the study has 

been reviewed and classified, EPA will determine whether or not it should be included in 

the DCI. The decision will be posted in the amitrole registration review public docket. 

The terrestrial field dissipation study continues to be listed as a data gap in this Final 

Work Plan document. 

 Reviews for the three remaining previously submitted environmental fate studies (GLNs 

835.2240, photodegradation in water; 835.2410, photodegradation in soil; and 835.4400, 

anaerobic aquatic metabolism) have been deferred until later in the registration review 

process. These studies have been removed from the list of data to be called-in, and if 

they are found to be unacceptable in the future once the reviews are completed, 

conservative assumptions (stability of amitrole to each of these processes) will be used 

for purposes of the ecological risk assessment. 

 Therefore, the following GLNs identified in the Preliminary Work Plan as anticipated 

data needs are no longer required: 835.2240, 835.2410, 835.4100, 835.4300, and 

835.4400. 

Lastly, the timeline provided in this Final Work Plan has been revised since the PWP to correct 

an error. The estimated timeframe for GLN 835.7100, ground water monitoring is 48 months, 

not 12 months as was erroneously listed in the Summary of Data Gaps table in the PWP. Also, 

in the PWP, 24 months was the longest study timeframe accounted for, but it should have been 

48 months for the ground water monitoring study. Incorporating the 48 month study into the 

“Registration Review for Amitrole – Projected Registration Review Timeline” extends the 

projected data submission and all subsequent dates by two years. A corrected timeline is 

included in this document. 

Comments Received on the Preliminary Work Plan:

The amitrole registration review docket was open for a 60-day public comment period beginning 

on June 29, 2011 and ending on August 29, 2011. During the public comment period, the 

Agency did not receive any public comments regarding the timeline or data requirements for 

amitrole as listed in the PWP. In the PWP, EPA also solicited comments on the specific topics 

of environmental justice, water body impairment, and trade irritants, but no comments or 

information were received on those issues. 

Risk Assessment and Data Needs:

The Agency will require data and conduct a comprehensive ecological risk assessment, including 

an endangered species assessment, for all uses of amitrole and its degradates of concern. For 
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human health, EPA will require data and conduct a dietary (drinking water only) assessment and 

revised occupational risk assessments during registration review. If toxicological 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 standard operating 

procedures or default exposure assumptions. Below is a summary of the issues relevant to the 

registration review of amitrole. 

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 all registered uses of amitrole and its 

degradates of concern will be conducted during registration review. The new assessment 

will incorporate the most up-to-date modeling methodologies, updated toxicological 

endpoints, and data submitted under the 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 determine 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 assessment concludes that a pesticide’s use “may 

affect” a listed species or its designated critical habitat, the Agency will consult with the 

U.S. Fish and Wildlife Service and/or National Marine Fisheries Service (the Services), 

as appropriate. 

 On January 19, 2011, the Center for Biological Diversity and the Pesticide Action 

Network North America filed a lawsuit in the United States District Court for the 

Northern District of California, against EPA for allegedly failing to undergo consultation 

with the Services regarding the effects of over 350 pesticides, including amitrole, on over 

200 endangered and threatened species throughout the United States (Center for 

Biological 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 will 

require the following studies for use in conducting a complete ecological risk assessment, 

including an endangered species assessment, for the registration review of amitrole. 

835.1410 – Volatility, laboratory 

835.4200 – Anaerobic soil metabolism 

835.6100 – Terrestrial field dissipation2,3

 

2

 EPA expects to finish its review of a previously submitted terrestrial field dissipation study in early 2012, prior to 

issuance of the data call-in. Once the study has been reviewed and classified, EPA will determine whether or not it 

should be included in the DCI. 

3

 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 per footnote 7 of 

40 CFR 150.1300. 
6

835.6200 – Aquatic field dissipation study4

835.7100 – Ground water monitoring 

850.1350 – Aquatic invertebrate life cycle toxicity (saltwater, mysid shrimp, A. 

bahia)

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

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

850.2100 – Acute avian oral toxicity test using a passerine species

850.4100 – Terrestrial plant toxicity, seedling emergence, Tier II

850.4150 – Terrestrial plant toxicity, vegetative vigor, Tier II 

Studies to be conducted 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, is a plant growth regulator and pesticide active 

ingredient (PC Code 014002) currently undergoing registration review (Docket ID: 

EPA-HQ-OPP-2007-1014). Because available data indicate that cyanamide may be more 

toxic to aquatic organisms than the parent amitrole, the three studies listed above are 

needed for use in conducting the planned registration review risk assessment for amitrole. 

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

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

submission of these studies would reduce uncertainty, and in the absence of these data, 

effects to salt water organisms would be assumed 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 ecological risk assessment for amitrole, EPA 

will require a chronic estuarine/marine invertebrate and fish early life stage studies to be 

conducted with cyanamide as listed above. 

The freshwater fish early life stage study (MRID 44076701) cited in the 2007 cyanamide 

problem formulation is classified 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, and therefore, these data are 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 be considered during the registration review of amitrole. 

 

4

 See footnote 7 of 40 CFR 150.1300. EPA is requiring only the environmental chemistry analytical methods and 

ILV portions of this guideline for water, rather than the full field dissipation study. 
7

 A prospective ground water monitoring study (GLN 835.7100) is required for amitrole 

based on its chemical properties (i.e. high solubility and low sorption coefficient) which 

indicate that it has high leaching potential. The presence of amitrole in groundwater, 

however, may also be affected by other factors, such as, national usage data, how 

amitrole use is distributed spatially, the number of retreatments, or the proximity of 

amitrole application sites to aquifers that are used for water supply. Due to the nature of 

amitrole’s use sites (agricultural rights-of way, industrial and construction sites, 

fencerows, along highways, railroads, public utilities), EPA does not have a clear 

understanding of the nature or scope of amitrole use. Because of these uncertainties and 

the potential that amitrole could leach into ground water, EPA is requiring the ground 

water monitoring study. However, if additional amitrole usage information and/or 

characterization is provided, EPA may reconsider the ground water monitoring data 

requirement. 

 Please refer to the December 7, 2011 document Registration Review – Addendum to 

Problem Formulation for the Ecological Risk and Drinking Water Exposure Assessments 

for Amitrole in the amitrole registration review docket (EPA-HQ-OPP-2011-0105) for a 

detailed discussion of the 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 expected during registration review because 

there are currently 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 amitrole was not previously conducted, and EPA 

will conduct one during registration review.

 Since there are no residential uses and no anticipated residential exposures from amitrole, 

residential handler and post-application exposure assessments are not expected during 

registration review. 

 Updates to the occupational handler exposure assessments using current standard 

operating procedures and exposure assumptions are expected during registration review 

for currently registered amitrole products. Inhalation exposures will be assessed, but a 

dermal exposure assessment is not expected because the endpoint selected from the 

dermal developmental toxicity study (1,500 mg/kg/day) is above the exposure expected 

based on the currently registered uses of amitrole. In addition to updating the three 

occupational handler scenarios assessed in the 1995 risk assessment, a handler 

assessment is expected to be performed during registration review for mixing, loading, 

and applying water-dispersible granules. This scenario has not been previously assessed. 
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 Occupational post-application inhalation exposures are expected to be negligible because 

re-entry is restricted until sprays have dried, and volatilization will be negligible. The 

dermal endpoint for an occupational post-application dermal exposure assessment is 

above the exposure expected based on the currently registered uses of amitrole. For these 

reasons, occupational post-application assessments for amitrole are not expected during 

registration review. 

 EPA will 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 subchronic 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 discussion of the risk assessments and data 

needs. 

Endocrine Disruptor Screening Program: 

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of its reregistration decision, EPA reviewed these data and selected 

the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard 

database. However, as required by FFDCA section 408(p), amitrole is subject to the endocrine 

screening part of the Endocrine Disruptor Screening Program (EDSP). 

EPA has developed the 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 
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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 67 

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 issue future EDSP orders/data callins, requiring the submission of EDSP screening assays for amitrole. For further information on 

the status of the EDSP, the policies and procedures, the list 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 timeline for the completion of amitrole’s registration 

review. 

Registration Review for Amitrole – Projected Registration Review Timeline

Activities Estimated Date 

Opening the Docket 

Open Docket and Public Comment Period 2011 – June 

Close Public Comment 2011 – August 

Case Development 

Final Work Plan 2011 – December 

Issue DCI 2012 – July – Sept. 

Data Submission 2016 – July – Sept. 

Open Public Comment Period for Draft Risk Assessments 2018 – Jan. – March 

Close Public Comment Period 2018 – April – June 

Registration Review Decision 

Open Public Comment Period for Proposed Registration Review 

Decision 

 2018 – July – Sept. 

Close Public Comment Period 2018 – Oct. – Dec. 

Registration Review Decision and Begin Post-Decision Follow-up 2019 

Total (years) 8 

Next Steps: 

As noted previously, the Agency will require several environmental fate, ecological effects, and 

human health studies through a data call-in, expected to be issued in late 2012. This new 

information will be used to conduct complete risk assessments for all amitrole uses. 
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SUMMARY OF DATA GAPS – AMITROLE:

The table below summarizes all data needs for amitrole as identified in this document, the 

Registration Review – Addendum to Problem Formulation for the Ecological Risk and Drinking 

Water Exposure Assessments for Amitrole dated December 7, 2011, and the Amitrole: Human 

Health Risk Scoping Document in Support of Registration Review dated June 13, 2011. 

Table 1. Data Needs for Amitrole Registration Review 

Guideline 

Number Data Needs Test 

Material 

Estimated 

Timeframe 

(Months 

from receipt 

of DCI) 

835.1410 Volatility, laboratory TEP 12 

835.4200 Anaerobic soil metabolism TGAI 24 

835.6100 Terrestrial field dissipation5,6 TEP 24 

835.6200 Aquatic field dissipation study7 TGAI 12 

835.7100 Ground water monitoring TEP 48 

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 degradate 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 degradate 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 degradate 12 

850.2100 Avian oral acute toxicity test using a passerine species TGAI 12 

850.4100 Terrestrial plant toxicity, seedling emergence, Tier II TEP 12 

850.4150 Terrestrial plant toxicity, vegetative vigor, Tier II TEP 12 

870.1300 Acute inhalation toxicity - rat TGAI 8 

870.3465 90-day inhalation - rat8 TGAI 24 

870.6200 Acute and subchronic neurotoxicity - rat TGAI 24 

870.7800 Immunotoxicity Study TGAI 12 

 

5

 EPA expects to finish its review of a previously submitted terrestrial field dissipation study in early 2012, prior to 

issuance of the data call-in. Once the study has been reviewed and classified, EPA will determine whether or not it 

should be included in the DCI. 

6

 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 per footnote 7 of 

40 CFR 150.1300. 

7

 See footnote 7 of 40 CFR 150.1300. EPA is requiring only the environmental chemistry analytical methods and 

ILV portions of this guideline for water. 8

 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.