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# Hexazinone Summary Document Registration Review: Initial Docket
March 2010

### TABLE OF CONTENTS

I. PRELIMINARY WORK PLAN ................................................................................. 4

II. FACT SHEET ........................................................................................................... 10



### Please Note

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

1. Hexazinone: Registration Review Scoping Do cument for Human Health Assessments. January 12, 2010.
2. EFED Registration Review Problem Form ulation for Hexazinone. January 12, 2010

. 3. Usage/Label Use Report for Hexazinone. June 16, 2009.

34 I. PRELIMINARY WORK PLAN

Introduction

The Food Quality Protection Act (FQPA) of 1996 mandated a re gistration review program. All pesticides distributed or sold in the United States generally must be registered by the U.S. Environmental Protection Agency (EPA or the Agency), 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 regist ration 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 th e statutory standard of no unreas onable 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 pe riodically reevaluates pesticides to make sure that as change occurs, products in the marketplace can be used safely. Information on this program is provided at www.epa.gov/oppsrrd1/registration_review/

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The Agency is implementing the registration re view program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rode nticide Act (FIFRA), and will review each registered pesticide every 15 years to determine wh ether it continues to m eet the FIFRA standard for registration. The Agency will consider bene fits information and data as required by FIFRA. The public phase of registration review begins wh en the initial docket is opened for each case. The docket is the Agency’s opportunity to stat e what it knows about the pesticide and what additional risk analyses and data it believes are needed to make a registration review decision. After reviewing and responding to comments and data received in the docket during this initial comment period, the Agency will develop and commit to a final work plan and schedule for the registration review of hexazinone.

Hexazinone is a herbicide that was first registered in the Un ited States in 1975 for general weed control in non-cropland areas, and is currently registered for use on alfalfa, blueberries, forest trees, pasture and range gr asses, ornamental plants, pinea pples, and sugarcane to control broadleaf weeds, grasses, and some woody plants. Hexazinone is a triazine herbicide, but it is structurally and toxicologically dissimilar to the other triazine herbicides such as atrazine. Therefore, hexazinone has not been in cluded in any cumulative assessment.

Anticipated Risk Assessment and Data Needs:

The Agency anticipates conducting an eco logical risk assessment for hexazinone, including an endangered species assessment. The Agency al so anticipates conducting human
health risk assessments for hexazinone. Below is a summary of the issues relevant to the registration review of hexazinone.

Ecological Risk:

• An environmental fate and effects risk assessment for hexazinone was completed in support of the 1994 Reregistration Eligibility Decision (RED).5 • The Agency has conducted a risk assessment th at supports a complete endangered species determination for the California Red-Legged Frog (CRLF) as well as Pacific salmon and
steelhead. The CRLF assessment resulted in a “Likely to Adversely Affect”
determination for both direct and indirect e ffects to the CRLF. The Agency concluded that hexazinone will not present a direct eff ect on Pacific salmon and steelhead or their
critical habitat. These assessments were submitted to the Services for initiation of formal
consultation.

• EPA anticipates needing the following guide line studies for hexazinone in order to conduct a complete environmental fate a nd ecological risk assessment during the registration review of hexazinone:

o 835.4100 Aerobic Soil Metabolism

o 835.4200 Anaerobic Soil Metabolism

o 835.4300 Aerobic Aquatic Metabolism

o 835.4400 Anaerobic Aquatic Metabolism

o 835.6100(7) Independent Laboratory Validation of Environmental Chemistry Analytical Method for Soil

o 835.6200(7) Environmental Chemistry An alytical Method for Water and an Associated Independent Laboratory Validation

o 850.2100 Avian Oral Toxic ity (Passerine species)

o 850.4100 Terrestrial Plant Toxicity, Ti er II (seedling emergence)

o 850.4150 Terrestrial Plant Toxicity, Tier II (vegetative vigor)

• Please refer to EFED Registration Review Problem Formulation for Hexazinone dated January 12, 2010, located in the hexazinone doc ket, for a detailed discussion of the anticipated ecological risk assessment needs.

Human Health Risk:

• A comprehensive human health risk a ssessment was conducted for the 1994 RED.

• The most recent dietary exposure assessment was conducted in association with the 2002 Tolerance Reassessment Progress and Risk Management Decision (TRED).

• The RED did not include a residential risk assessment. While there are no registered residential uses of hexazinone, it is registered for use on indust rial turf grass, and current
labels do not restrict this use in residential settings . Since this could potentially result in post-application residential exposure, the Ag ency intends to conduct a residential risk assessment during registration review. A ne w aggregate risk assessment will also be
needed.

• The Agency intends to conduct a drinking water exposure assessment for registration
review.

• The hexazinone tolerance expression (40 CFR 180.396) will be reviewed during registration review to ensure that it appropr iately covers the metabolites and degradates of hexazinone and that it specifies the residues to be measured for each commodity.

• The Agency anticipates an updated occupati onal and occupational post-application risk
assessments will be needed for hexazinone. The new occupational post-application risk assessment will use data from the Agricultural Reentry Task Force to update the exposure
estimates based on current transfer coefficients. In addition, the existing 48 hour Restricted Entry Interval (REI) will be revisited.6 • The Agency anticipates that a revised dietary assessment will be needed.

• The toxicity and residue chemistry database s are complete with the exception of the following studies, which the Agency anticipates requiring in order to conduct a complete
human health assessment:

○ 870.3465 28-Day Inhalation Toxicity

○ 870.7800 Immunotoxicity (rats)

○ 870.6200 Neurotoxicity Battery (acu te and subchronic studies)

○ 860.1900 Field Rotational Crops (corn and wheat)

• Please refer to Hexazinone: Registration Review Sc oping Document for Human Health

Assessments dated January 12, 2010, located in the hexazinone docket, for a detailed discussion of the anticipated human health risk assessment needs.

Endocrine Disruptor Screening Program (EDSP): As required under FFDCA section 408(p), EP A has developed the Endocrine Disruptor Screening Program (EDSP) to determine whether certain substances (inc luding pesticide active and other ingredients) may have an effect in humans or wildlife si milar to an effect produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP employs a two-tiered ap proach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays that provide scientific information to help inform EPA on the potential for a chemical to interact with the estrogen, androgen, and/or thyroid hormone systems. Based on the results of the Tier 1 screening battery EPA may require further testing in Tier 2 assays to characterize the chemical’s potential to cause adverse effects as a conseque nce of such interaction(s).

Between October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals, which contains 58 pesticid e active ingredients and 9 inert ingredients. This group of chemicals was selected based on the potential for human exposure through pathways such as food and water, residential activity, and certain post- application agricultural scenarios. The chemicals in this first group of pesticide active ingredients and inert ingredients should not be construed to be endocrine disrupto rs since they were selected based on exposure potential alone.

Hexazinone is not among the group of 58 pesticide active ingredients receiving test orders. Under FFDCA sec. 408(p) the Agency must screen all pesticide chemicals. Accordingly, EPA anticipates issuing future EDSP orders/data call-i ns for all Registration Re view cases, including those for which EPA has already opened a Regi stration Review docket for a pesticide active ingredient.

For further information on the status of the ED SP, the policies and procedures, the list of 67 chemicals, the test guidelines and the Tier 1 screening battery, pleas e visit our website: http://www.epa.gov/endo/.

Timeline: EPA has created the following estimated time line for the completion of the hexazinone registration review.7 Registration Review for Hexazinone– Pr ojected Registration Review Timeline

Activities Estimated Date Opening the docket Open Docket and Public Comment Period 2010 – March

Close Public Comment 2010 – May Case Development

Final Work Plan 2010 – August

Issue DCI 2011 – Apr.- June
Data Submission 2013 – Apr. - June Open Public Comment Period for Preliminary Risk Assessments 2014 – Oct. - Dec.
Close Public Comment Period 2015 – Jan. – Mar. Registration Review Decision Open Public Comment Period for Proposed Registration Review
Decision 2015 – Apr. – June.

Close Public Comment Period 2015 – July – Sept. Final Registration Review Decision a nd Begin Post-Decision Follow-up 2016 Total (years) 6

Guidance for Commenters The public is invited to comme nt on EPA’s preliminary regist ration review work plan and rationale. The Agency will carefully consid er all comments as well as any additional information or data provided in a timely manne r prior to issuing a fi nal work plan for the
hexazinone 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 Levels (MRLs) or disparitie s between U.S. tolerances and MRLs in key export markets, providing as much specificity as possible regarding the nature of the concern.

Water Quality
Hexazinone is not identified as a cause of im pairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act, based on information provided at http://iaspub.epa.gov/tmdl_waters10/attains_ nation_cy.cause_detail_303d?p_cause_group_id=88

5 . In addition, no Total Maximum Daily Loads (TMDL) have been developed for hexazinone, based on information provided at http://iaspub.epa.gov/tmdl_waters10/attains_ nation.tmdl_pollutant_de tail?p_pollutant_group_id =885&p_pollutant_group_name=PESTICIDES . More information on impaired water bodies and
TMDLs can be found at http://www.epa.gov/owow/tmdl/ . The Agency invites submission of water quality data for this pesticide. To the exte nt possible, data should conform to the quality standards in Appendix A of the OPP Standard Operating Procedur e: Inclusion of Impaired Water Body and Other Water Quality Data in OPP’s Regist ration Review Risk Assessment and8 Management Process (see: http://www.epa.gov/oppsrrd1/regist ration_review/water_quality_sop.htm ) in order to ensure they can be used quantitatively or qualitati vely in pesticide risk assessments.

Environmental Justice
EPA seeks to achieve environmenta l justice, the fair tr eatment and meaningful involvement of all people, regardless of race, color, national origi n, or income, in the deve lopment, implementation, and enforcement of environmental laws, regulati ons, and policies. To help address potential environmental justice issues, the Agency seeks information on 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 hexazinone, compared to the general population. Please comment if you are aware of any sub-populations that may have atyp ical or unusually high exposure compared to the general population.

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

1. Confirmation of the following label information.

a. sites of application
b. formulations

c. application methods and equipment
d. maximum application rates in units relate d to mass per unit area of treatment zone

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 ., geographical distribution of relevant uses).

3. Use history.

4. Median and 90 th percentile reported use rates from usage data – national, state, and
county.
5. Application timing (date of firs t application and application intervals) by use – national, state, and county.

6. Sub-county use site data.

7. Usage/use information for non-agricultural uses ( e.g ., warehouses, railroad cars, domestic dwellings).

8. Directly acquired county-level usage data (not derived from state level data).

a. maximum reported use rate 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.9 11. Ecological incidents (non-target plant damage and avian, fish, rept ilian, amphibian and mammalian mortalities) not al ready 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 issue a Final Work Plan for hexazinone.10 II. FACT SHEET

Background Information :

• Hexazinone Registration Revi ew Case Number: 0266

• Hexazinone PC Code: 107201; CAS#: 51235-04-2

• Technical Registrant: E. I. du Pont de Nemours, Inc.

• Hexazinone was first registered in 1975.

• The Reregistration Eligibility Decision doc ument (RED) for hexazinone was signed in September 1994. The RED concluded that re gistered pesticide products containing hexazinone did not pose unreasona ble risks to humans or the environment when used according to the label, including incorporation of risk reduction measures specified in the

RED.

• The TRED for hexazinone was signed in 2002.

• Tolerances for hexazinone range from 0.1 ppm to 10 ppm [40 CFR 180.396]

• Pesticide Re-evaluation Division (PRD), Ch emical Review Manager (CRM) Dana L. Friedman ( friedman.dana@epa.gov )

• Registration Division (RD) Contact: Eugene Wilson ( wilson.eugene@epa.gov )

Use & Usage Information:

• Hexazinone is registered for use as an he rbicide to control a number of weeds and, grasses, and some woody plants in agricu ltural and non-agricultura l areas. While there are no registered residential uses of hexazi none, it is applied to commercial turf that
could be used in residential areas.

• According to data averaged from the United St ates Department of Agriculture’s National Agricultural Statistics Service, National Pesticide Use Database, California Department of Pesticide Regulation, and private market research, approximately 350,000 lbs a.i. are used on agricultural use sites per year. Use da ta are not available fo r non-agricultural use sites, which would include use in reforestation.

Recent Actions:

• The Agency has conducted a risk assessment th at supports a complete endangered species determination for the California Red-Legged Frog (CRLF) as well as Pacific salmon and
steelhead. The CRLF assessment resulted in a “Likely to Adversely Affect”
determination for both direct and indirect e ffects to the CRLF. The Agency concluded that hexazinone will not present a direct eff ect on Pacific salmon and steelhead or their
critical habitat. These assessments were submitted to the Services for initiation of formal
consultation.

Ecological Risk Assessment Status : Please refer to EFED Registration Review Problem Formulation for Hexazinone , located in the hexazinone docket at regulations.gov (EPA- HQ-OPP-2009-0755), for a discussion of the key findings of the most recent ecological risk assessment for hexazinone. A summary follows:11 • An environmental fate and effects risk assessment for hexazinone was completed in support of the 1994 RED. It noted ecologi cal risks of concern for non-target, and terrestrial and aquatic plants.

• The 1994 reregistration decision for hexazinone specified a number of measures to reduce ecological risk, incl uding groundwater advisory label language, spray drift advisory label language, and reduced maximum application rates.

Human Health Risk Assessment Status:
Please refer to Hexazinone: Registration Review Sc oping Document for Human Health

Assessments , located in the hexazinone docket at regulations.gov (EPA-HQ-OPP-2009-0755), for a discussion of the key findings of the mo st recent human health risk assessment for hexazinone. A summary follows:

Hazard Characterization:

• In acute toxicity studies, hex azinone is Toxicity Category II I via the oral exposure route and Toxicity Category IV via th e dermal irritation, acute dermal, and inhalation routes of exposure. Hexazinone is Toxicity Category I vi a the eye irritation rout e of exposure. It
is not a dermal sensitizer.

• Hexazinone is classified as D, not classifiable for human carcinogenicity.

Dietary (Food and Drinking Water):

• The most recent dietary exposure assessment was conducted in association with the 2002 TRED. Dietary risk estimates for hexazinone were below EPA’s level of concern for the general population and a ll population subgroups.

Residential:

• The 1994 RED did not assess residential scen arios because there are no registered residential uses of hexazinone. It is, however , registered for use on industrial turf grass,
and current labels do not restrict th is use in residen tial settings.

Aggregate:

• Since there are no registered residential uses of hexazinone, only food and drinking water were taken into account in the aggregate risk assessment.

Occupational :

• No occupational handler and post-application exposure risk estimates were quantitatively assessed as part of the RED as no toxicological endpoints were identified at that time.

• Future hexazinone risk assessments will re ly in part on data from human studies comprising 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 in these multi-pes ticide generic exposure databases, and on the
basis of available evidence ha s found them to have been ne ither fundamentally unethical nor significantly deficient re lative to standards of ethi cal research conduct prevailing when they were conducted. There is no regul atory barrier to con tinued reliance on these12 studies, and all applicable requirements of EPA’s Rule for the Protection of Human Subjects of Research (40 CFR Pa rt 26) have been satisfied.

Cumulative:

• While hexazinone is a triazine herbicid e, the preliminary evaluation of common mechanisms of toxicity indicated that hexa zinone does not have a common mechanism of toxicity sufficient to be grouped with the triazines for a cumulative assessment. Therefore, hexazinone has not been in cluded in any cumulative assessment.

Incidents:

Ecological:

• There were nine incident reports for hexazi none in the Agency’s Ecological Incident Information System (EIIS). All reported in cidents were associated with non-target exposure to terrestrial plants.

Human:

• The OPP Incident Database System (IDS) wa s searched for human incidents involving
hexazinone in the United States from 2002 to the present. IDS includes reports of incidents from various sources, including mandatory FIFRA Section 6 (a) (2) reports from registrants, other federal and state hea lth and environmental agencies and individual
consumers. This search indicates that ei ght incidents were reported. However, upon review, only two were identified as defin ite, probable, or po ssible cases involving hexazinone exposure.

Data Call-In Status:

• A Data Call-In (DCI) was issu ed in 1995 in conjunction with the 1994 hexazinone RED, and in 2004 in conjunction with the hexazinone TRED.

• The data requirements for field accumulation in rotational crops are partially satisfied. Extended field rotational crop trials for corn and sorghum stover and wheat straw are required to support a 12-month rotational interval and a tolerance for inadvertent
hexazinone residues.

Tolerances and International Harmonization:

• Canadian and CODEX MRLs have not been established for hexazinone.

• The hexazinone tolerance expression in 40 CFR 180.396 will be reviewed during registration review to ensure that it appropr iately covers the metabolites and degradates of hexazinone and that it specifies the residues to be measured for each commodity.

Labels : Hexazinone labels can be obtained from the Pe sticide Product Label System (PPLS) website: http://oaspub.epa.gov/pestlabl/ppls.home

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