2

Ametryn Preliminary Work Plan – Table of Contents 

Overview 3 

Anticipated Data Needs 4 

Statutory and Regulatory Authority 5 

Ametryn Facts 5 

Use and Usage Information 6 

Recent Actions 7 

Anticipated Risk Assessments for Registration Review 7 

Timeline 9 

Next Steps 10 

Appendix – Additional Areas Considered in the Ametryn Registration Review 11 

References:

This Preliminary Work Plan summarizes the Environmental Protection Agency's current position 

based on the following documents: 

1. Preliminary Problem Formulation for Environmental Fate, Ecological Risk, Endangered 

Species, and Human Health Drinking Water Exposure Assessments for Ametryn. A. Sayer. 

May 14, 2013. 

2. Ametryn. Human Health Risk Scoping Document in Support of Registration Review. K. 

Lowe. May 9, 2013. 

3. Ametryn: Review of Human Incident Reports. S. Recore. January 31, 2013. 

4. BEAD Ametryn Profile for Registration Review: Ametryn. S. Ratnayake. March 30, 2012.

5. Ametryn Screening Level Usage Analysis. January 12, 2012.

6. PRD Label Data Report: Food/Feed & Non-Food/Non-Feed Uses Considered in 

Registration Review Work Planning. November 14, 2012.

These and other supporting documents for the ametryn registration review case may be found in 

the docket EPA-HQ-OPP-2013-0249 at http://www.regulations.gov. 
3

OVERVIEW

The docket for ametryn is now open, initiating the first public comment period for this 

registration review (docket number EPA-HQ-OPP-2013-0249). Ametryn is a triazine herbicide 

used for selective control of broadleaf and grassy weeds in corn, pineapple, and sugarcane. 

There are no non-agricultural or residential uses registered. This Preliminary Work Plan (PWP) 

document explains what EPA's Office of Pesticide Programs knows about ametryn, highlighting 

anticipated data and assessment needs, identifying the types of information that would be 

especially useful to the Agency in conducting the review, and providing an anticipated timeline 

for completing the registration review for ametryn. 

 

The registration review process was designed to include a public participation component to 

solicit input from interested stakeholders. The Agency intends, by sharing this information in the 

docket, to inform the public of what it knows about ametryn and what types of new data or other 

information would be helpful for the Agency to receive as it moves toward a decision on 

ametryn. The Agency encourages all interested stakeholders to review the PWP and Appendix 

and to provide comments and additional information that will help the Agency’s decisionmaking process for ametryn. In addition to general areas on which persons may wish to 

comment, there are some areas identified in the PWP and Appendix about which the Agency 

specifically seeks comments and information. Interested stakeholders could include: 

environmental non-profit or interest groups; pesticide manufacturers; agricultural labor or 

commodity groups; commercial, institutional, residential, and other users of pesticides; or the 

public at large. 

The Preliminary Work Plan begins by listing the anticipated data needs for ametryn. Next, it 

discusses the statutory and regulatory authority for Registration Review. Then the document 

provides ametryn facts, use and usage information, recent actions, the anticipated risk 

assessments, and a projected registration review timeline for ametryn. Finally, the Appendix to 

this document includes identification and discussion of some areas that are considered generally 

in Registration Review along with some additional ametryn case-specific information. 

 
4

ANTICIPATED DATA NEEDS

Table 1 below summarizes anticipated data needs for ametryn. For additional discussion of the 

anticipated data needs, see the: Preliminary Problem Formulation for Environmental Fate, 

Ecological Risk, Endangered Species, and Human Health Drinking Water Exposure Assessments 

for Ametryn and Ametryn: Human Health Risk Scoping Document in Support of Registration 

Review. 

Table 1: Anticipated Data Needs for the Ametryn Registration Review 

Guideline 

Number1,2 Study Title1 Test Material 

Estimated 

Timeframe 

(Months from 

receipt of DCI) 

835.2240 Photodegradation in water TGAI 12 

835.4100 Aerobic soil metabolism TGAI 24 

835.4300 Aerobic aquatic metabolism TGAI 24 

850.4500 Algal toxicity TEP 12 

850.4550 Cyanobacteria toxicity TEP 12 

870.3465 90-day inhalation3 TGAI 24 

870.7800 Immunotoxicity4 TGAI 12 

TGAI = technical grade active ingredient; TEP = typical end-use product; 1

 On June 27, 2012, EPA announced certain revisions in harmonized guideline series 850 – Ecological Effects Tests 

– including renumbering and other designations or changes for some guideline studies. See “Final Test Guidelines; 

OCSPP 850 Series; Notice of Availability” 77 FR 38282, June 27, 2012. 

http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0154-0028 2 Page 31 of the Problem Formulation incorrectly indicates environmental chemistry methods (ECM) and associated 

independent laboratory validation (ILV) for water (Guideline 850.6100) are needed for ametryn. Acceptable ECM 

and ILVs for soil, sediment, and water have been submitted for ametryn, and therefore, EPA does not anticipate 

requiring Guideline 850.6100. 

3 A 28-day inhalation toxicity study will be sufficient. Therefore, the study duration can be reduced from 90 days to 

28 days. 

4 Recently, OPP published the findings of its retrospective analysis of immunotoxicity studies submitted to the 

Agency, concluding that none of the studies included in the analysis resulted in a Point of Departure (POD) that is 

lower than the PODs selected from other available guideline toxicology studies 

(http://www.epa.gov/pesticides/regulating/immunotoxicity-retro-analysis.pdf). EPA will consider requests for 

waivers for this study, particularly in light of the retrospective analysis. A weight-of-evidence rationale will be 

considered relative to the chemical’s toxicological profile, primary target organ system(s) and mode of toxic action, 

and any immuno-related data available from structurally-related compounds. 
5

STATUTORY AND REGULATORY AUTHORITY

The Food Quality Protection Act (FQPA) of 1996 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 on EPA’s website.1

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 regulations governing registration review begin at 40 CFR 155.40. The 

Agency will consider benefits information and data as required by FIFRA. The public phase of 

registration review begins when the initial docket is opened for each case. The docket is the 

Agency’s opportunity to state what it knows about the pesticide and what additional risk analyses 

and data or information it believes are needed to make a registration review decision. After 

reviewing and responding to comments and data received in the docket during this initial 

comment period, the Agency will develop a Final Work Plan (FWP) and anticipated schedule for 

the registration review of ametryn. 

AMETRYN FACTS

Table 2 provides a summary of the current regulatory status for ametryn. 

Table 2: Ametryn Facts 

PC code 080801 

Case Number 7036 

CAS Number 834-12-8 

Year first registered 1964 

Pesticide Type Herbicide 

Ametryn class Triazine 

Reregistration Eligibility 

Decision (RED) 

September 2005 

 

1

 http://www.epa.gov/oppsrrd1/registration_review/ 
6

Table 2: Ametryn Facts 

Cumulative group Not applicable. Ametryn has not been identified as a member of a 

cumulative group that shares a common mechanism of toxicity. 

Ametryn was not included in the 2006 triazine cumulative risk 

assessment that included the pesticide active ingredients atrazine, 

simazine, propazine, and the metabolites desethyl-s-atrazine (DEA), 

desisopropyl-s-atrazine (DIA), and diaminochlorotriazine (DACT), 

because it does not share the same toxicity profile as these 

chlorotriazines. 

40 CFR Citation Tolerances for ametryn are established in 40 CFR §180.258(a). 

Dual-use Ametryn is registered for conventional pesticidal uses only and has 

no registered antimicrobial or biopesticidal uses. 

Non-pesticidal uses There are no identified non-pesticidal uses of ametryn. 

Pesticide Re-evaluation 

Division, Ametryn 

Review Manager 

Molly Clayton 

clayton.molly@epa.gov

703-603-0522 

Registration Division, 

Product Manager 

Kable Bo Davis 

davis.kable@epa.gov

703-306-0415 

USE AND USAGE INFORMATION

Table 3 summarizes the use and usage information for ametryn. Please see the memo BEAD 

Ametryn Profile for Registration Review: Ametryn in the registration review docket for more 

details. 

Table 3: Ametryn Use and Usage Information

Summary of Use Ametryn is a triazine herbicide used for selective control of 

broadleaf and grassy weeds in corn, pineapple, and sugarcane. 

There are no non-agricultural or residential uses registered. 

Ametryn can be applied as pre-emergence and as a post-emergence 

directed spray.

Use Sites Pineapple, sugarcane, and corn (field and pop) 

Summary of Usage Based on private market usage data from 2000-2010, usage 

averaged approximately 200,000 pounds active ingredient (a.i.) for 

350,000 acres treated.

Formulation Type(s) Ametryn is formulated as water dispersible granules.

Application Method(s) It can be applied by conventional ground sprayers. Aerial 

application is allowed in Florida for sugarcane only.

Technical Registrant(s) Syngenta Crop Protection, LLC 

No. of Registrations Two Section 3 products2

Restricted Use No 

 

2

 Section 3 product labels can be obtained from the Pesticide Product Label System (PPLS) website 

(http://oaspub.epa.gov/pestlabl/ppls.home). 
7

Guidance for Commenters: Additional areas of use and usage related information requested 

for this registration review, and of particular interest to EPA, are described below. 

 Confirmation of the following label information: sites of application; formulations; 

application methods and equipment; maximum application rates; frequency of 

application, application intervals, and maximum number of applications per season; and 

geographic limitations on use. 

 Use distribution (e.g., acreage and geographical distribution of relevant use sites). 

 Median and 90th percentile reported use rates (lbs ai/A) from usage data – national, state, 

and county. 

 Typical application timing (date of first application and application intervals) – national, 

state, and county. 

 Usage/use information for non-agricultural uses. 

 Typical application interval (days). 

 State or local use restrictions. 

 Foreign technical registrants not listed above who supply technical ametryn to the US 

market. 

RECENT ACTIONS

In November 2012, EPA approved a 24c Special Local Need (SLN) registration for use of 

ametryn on pineapple in Hawaii. While ametryn is already approved for use nation-wide on 

pineapple, the SLN includes different use directions for pineapples in Hawaii, such as modified 

spray drift language. 

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW

The most recent comprehensive human health risk assessment for ametryn was completed in 

2005 in preparation for the RED. The most recent ecological and environmental fate risk 

assessment was completed in 2005 for the same purpose. Findings and conclusions from these 

risk assessments are summarized in the Preliminary Problem Formulation for Environmental 

Fate, Ecological Risk, Endangered Species, and Human Health Drinking Water Exposure 

Assessments for Ametryn and Ametryn: Human Health Risk Scoping Document in Support of 

Registration Review. 

During registration review, the Agency anticipates the need to conduct a comprehensive 

ecological risk assessment, including an endangered species assessment, for all uses of ametryn. 

For human health, EPA anticipates the need to conduct revised dietary and occupational risk 

assessments during registration review. If toxicological endpoints or points of departure are 

revised, they will be considered in the new assessments, as well as any changes to the standard 

operating procedures or default exposure assumptions. 

Table 4 below summarizes the anticipated registration review risk assessments based on the 

EFED Problem Formulation and HED Scoping Document. 
8

Table 4: Anticipated Risk Assessments for the Ametryn Registration Review 

Type of Risk Assessment Conduct? Notes 

Ecological and Environmental Fate 

Comprehensive ecological 

(species to be assessed 

include terrestrial and aquatic 

organisms), including 

endangered species 

Y It is anticipated that the parent ametryn will be 

considered the stressor of concern for the terrestrial 

exposure assessment. For the aquatic exposure 

assessment, in the absence of data on the toxicity of 

degradates NOA 428383 and NOA 423271, it is 

anticipated that these degradates and the parent 

ametryn will be considered the stressors of concern 

using the total toxic residue (TTR) approach. For 

additional information, see page 25 of the Problem 

Formulation. 

Incidents Will check for 

updates 

No ecological incidents reported for ametryn; see 

page 24 of the Problem Formulation. 

Human Health 

Dietary 

Food Y EPA anticipates updating the dietary assessment 

during registration review to take into account any 

new toxicity or exposure data, changes to safety 

factors, or changes in standard risk assessment 

operating procedures. 

Drinking water N 

Occupational 

Handlers (mixers, loaders, 

applicators) 

Y EPA anticipates updating the occupational assessment 

during registration review to take into account any 

new toxicity or exposure data, changes to safety 

factors, or changes in standard risk assessment 

operating procedures. 

Post-application Y 

Residential 

Handlers N Ametryn is not registered for residential use, 

registered uses are not anticipated to result in 

residential exposure, and therefore, a residential risk 

assessment is not anticipated to be required. 

Post-application N 

Other 

Aggregate Y Evaluates the combined risk from dietary and 

residential exposures. Since there are no residential 

uses, EPA anticipates that the aggregate assessment 

will be updated to take into account any changes to 

dietary risk estimates only. 

Cumulative N Ametryn has not been identified as a member of a 

cumulative group that shares a common mechanism 

of toxicity. See page 6 of this document for 

additional details. 
9

Table 4: Anticipated Risk Assessments for the Ametryn Registration Review 

Tolerances Y Tolerances for ametryn are established under 40 CFR 

§180.258. EPA anticipates updating the residue 

definition for the tolerance expression for ametryn in 

accordance with current policy on tolerance 

definitions. 

Incidents Will check for 

updates 

For a discussion of reported human incidents for 

ametryn, see page 10 of the Scoping Document and 

the Ametryn: Review of Human Incident Reports. 

Guidance for Commenters: Additional ecological information requested for this 

registration review, and of particular interest to EPA, is described below. 

 Ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian and 

mammalian mortalities) not already reported to the Agency. 

 Water quality monitoring data (see Appendix for further details). 

TIMELINE

EPA has created the following estimated timeline for the completion of the ametryn registration 

review in Table 5 below. 

Table 5: Projected Ametryn Registration Review Timeline

Activities Estimated Date

Opening the Docket 

Open Docket and 60-day Public Comment Period 2013 – June 

Close Public Comment 2013 – August 

Case Development 

Final Work Plan 2013 – November 

Issue DCI 2014 July - September 

Data Submission 2016 July - September 

60-day Public Comment Period for Draft Risk 

Assessments3

2018 January – March 

Registration Review Decision 

60-day Public Comment Period for Proposed 

Registration Review Decision 

2018 July – September 

Registration Review Decision and Begin Post-Decision 

Follow-up 

2019 

Total (years) 6 

  

 

3

 The regulations governing Registration Review require the Agency to provide a public comment period of at least 

30 calendar days for draft risk assessments; see 40 CFR Part 155.53(c). The Agency plans to provide a 60 calendar 

day public comment period for draft risk assessments as a general standard of practice. 
10

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 issue a Final Work Plan for the registration 

review of ametryn.

 
11

Appendix – Additional Areas Considered in the Ametryn Registration Review

PUBLIC COMMENTS AND FEEDBACK:

Guidance for Commenters: The areas below highlight topics of special interest to the Agency 

where your comments, data submissions, or reference to sources of additional information could 

be of particular use.

Trade Irritants: 

Through the registration review process, the Agency intends to solicit information on trade 

irritants and, to the extent feasible, take steps toward facilitating irritant resolution. The Agency 

will work to harmonize tolerances and international maximum residue limits (MRLs) and may 

modify tolerance levels to do so, when possible. Growers and other stakeholders are asked to 

comment on any trade irritant issues resulting from lack of MRLs or disparities between U.S. 

tolerances and MRLs in key export markets, providing as much specificity as possible regarding 

the nature of the concern 

Water Quality: 

Ametryn is not identified as a cause of impairment for any water bodies listed as impaired under 

section 303(d) of the Clean Water Act.4

 In addition, no Total Maximum Daily Loads (TMDL) 

have been developed for ametryn.5 More information on impaired water bodies and TMDLs can 

be found at the Agency’s website.6 The Agency invites submission of water quality data for 

this pesticide. To the extent possible, data should conform to the quality standards in Appendix 

A of the OPP Standard Operating Procedure: Inclusion of Impaired Water Body and Other

Water Quality Data in OPP’s Registration Review Risk Assessment and Management Process7

 in 

order to ensure they can be used quantitatively or qualitatively in pesticide risk assessments. 

Environmental Justice: 

EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all 

people, regardless of race, color, national origin, or income, in the development, implementation, 

and enforcement of environmental laws, regulations, and policies. To help address potential 

environmental justice issues, the Agency seeks information on any groups or segments of the 

population who, as a result of their location, cultural practices, or other factors, may have 

atypical, unusually high exposure to ametryn compared to the general population. Please 

comment if you are aware of any sub-populations that may have atypical, unusually high 

exposure compared to the general population.

 

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

5

http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant_

group_name=PESTICIDES

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

7 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm
12

ENDANGERED SPECIES:

A risk assessment that supports a complete endangered species determination has not been 

conducted for ametryn. The ecological risk assessment planned during registration review will 

allow the Agency to determine whether use of ametryn 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. 

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 for ametryn, 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), ametryn 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 

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. Ametryn 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 ametryn. 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.8

 

8 http://www.epa.gov/endo/
13

HUMAN STUDIES:

Occupational 

Past ametryn 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, involving exposure to many different pesticides, comprise generic pesticide 

exposure databases such as the Pesticide Handlers Exposure Database (PHED) and the 

Agricultural Reentry 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 relative to the ethical standards prevailing at the time the research was conducted. All 

applicable requirements of EPA’s Rule for the Protection of Human Subjects of Research (40 

CFR Part 26) have been satisfied, and there is no regulatory barrier to continued reliance on 

these studies.