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



## Amitrole Final Work Plan Registration Review

December 20113 

### 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 incl udes 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 re gistration 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 ma ke a registration review decision.

The Agency’s implementation of the registrati on review program requi res review of each registered pesticide every 15 years to determin e whether it continues to meet the Federal Insecticide, Fungicide, and Rode nticide Act (FIFRA) standard for registration. Changes in science, public policy, and pestic ide use practices occur over time. The registration review program is intended to make sure that, as the ab ility to assess risk evolves and as policies and practices change, all registered pesticides contin ue to meet that statutory standard. The public phase of registration review begins when the in itial docket is opened for each case. Information on this program is provided on the Agency’s website 1

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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.

Updates Since the Summary Document was Issued:

In letters dated August 16, August 31, and Se ptember 9, 2011, Nufarm Americas Inc., the technical registrant for amitr ole, 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, aerobi c aquatic metabolism, and 835.6100,

terrestrial field di ssipation 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 tw o environmental fate studies which were

noted as “in review” in the June 2011 Su mmary Document. Re views of GLNs 835.4100,

1 http://www.epa.gov/oppsrrd1/registration_review/4 aerobic soil metabolism and 835.4300, aerobic aqua tic 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 di ssipation, which was also noted as “in review” in the Summary Document, is not yet co mplete. EPA expects to finish its review of that study in early 2012, prio r 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 amitrol e 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 wa ter monitoring is 48 months, not 12 months as was erroneously listed in the Su mmary of Data Gaps table in the PWP. Also, in the PWP, 24 months was the longest study timef rame 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 – Projecte d 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 op en 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 rega rding the timeline or data requirements for amitrole as listed in the PWP. In the PWP, EP A also solicited comments on the specific topics of environmental justice, wa ter body impairment, and trade i rritants, 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. For5 human health, EPA will require data and conduct a dietary (drinking water only) assessment and revised occupational risk assessments during regist ration review. If toxicological endpoints or points of departure are revised based on the data that are required for re gistration review, they will be considered in the new assessment, as well as any changes to the standard operating procedures or default exposure assumptions. Belo w 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 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 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 EP A 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 Un ited 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 conducti ng a complete ecological risk assessment, including an endangered species assessment, for the regist ration review of amitrole.

835.1410 – Volatility, laboratory

835.4200 – Anaerobic soil metabolism 835.6100 – Terrestrial field dissipation 2,3

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 re viewed 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 study 4
835.7100 – Ground water monitoring 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 test using a passerine species 850.4100 – Terrestrial plant toxicity , seedling emergence, Tier II 850.4150 – Terrestrial plant toxic ity, vegetative vigor, Tier II

Studies to be conducted with am itrole’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 unde rgoing 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 regist ration review risk assessment for amitrole.

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

estuarine/marine fish and invertebrate te sts. 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 will require a chronic estuarine/marine invertebra te and fish early life stage studies to be conducted with cyanamide as listed above.

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, 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 sol ubility 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 f actors, such as, national usage data, how amitrole use is distributed spatially, the num ber 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 amitrol e use. Because of these uncertainties and the potential that amitrole coul d leach into ground water, EPA is requiring the ground water monitoring study. However, if additional amitrole usage information and/or characterization is provide d, 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 Ec ological 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 assessm ent is not expected during registration review because there are currently no register ed 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 was not previously conducted, and EPA will conduct one during registration review.

 Since there are no residential us es and no anticipated resident ial exposures from amitrole, residential handler and post -application exposure assessmen ts are not expected 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. 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/k g/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 dur ing registration review for mixing, loading, and applying water-dispersible granules. This scenario has not been previously assessed.8  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. The 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 amitrol e 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 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 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, and9 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 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/

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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 – 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 se veral environmental fate, ecological effects, and human health studies through a da ta call-in, expected to be is sued in late 2012. This new information will be used to conduct complete risk assessments for all amitrole uses.10 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 Form ulation for the Ecologic al 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 Amit role 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 dissipation 5,6 TEP 24

835.6200 Aquatic field dissipation study 7 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 - rat 8 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 re viewed 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 no t expected to exceed 28 days.