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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 summarize the Environmental Protection Agency’s 

current position based on the following documents: 

1. Hexazinone: Registration Review Scoping Document for Human Health Assessments. 

January 12, 2010. 

2. EFED Registration Review Problem Formulation for Hexazinone. January 12, 2010. 

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

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I. PRELIMINARY WORK PLAN 

Introduction

The Food Quality Protection Act (FQPA) of 1996 mandated a registration 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 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 at www.epa.gov/oppsrrd1/registration_review/. 

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 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 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 United 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 grasses, ornamental plants, pineapples, 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 included in any cumulative assessment. 

Anticipated Risk Assessment and Data Needs:

The Agency anticipates conducting an ecological risk assessment for hexazinone, 

including an endangered species assessment. The Agency also 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). 
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• The Agency has conducted a risk assessment that 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 effects to the CRLF. The Agency concluded 

that hexazinone will not present a direct effect 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 guideline studies for hexazinone in order to 

conduct a complete environmental fate and 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 Analytical Method for Water and 

an Associated Independent Laboratory Validation 

o 850.2100 Avian Oral Toxicity (Passerine species) 

o 850.4100 Terrestrial Plant Toxicity, Tier 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 docket, for a detailed discussion of the 

anticipated ecological risk assessment needs. 

Human Health Risk: 

• A comprehensive human health risk assessment 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 industrial turf grass, and current 

labels do not restrict this use in residential settings. Since this could potentially result in 

post-application residential exposure, the Agency intends to conduct a residential risk 

assessment during registration review. A new 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 appropriately covers the metabolites and degradates 

of hexazinone and that it specifies the residues to be measured for each commodity. 

• The Agency anticipates an updated occupational 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. 
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• The Agency anticipates that a revised dietary assessment will be needed. 

• The toxicity and residue chemistry databases 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 (acute and subchronic studies)

○ 860.1900 Field Rotational Crops (corn and wheat)

• Please refer to Hexazinone: Registration Review Scoping 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), EPA has developed the Endocrine Disruptor 

Screening Program (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 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 consequence 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 pesticide 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 disruptors 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-ins for all Registration Review cases, including 

those for which EPA has already opened a Registration Review docket for a pesticide active 

ingredient. 

For further information on the status of the EDSP, the policies and procedures, the list of 67 

chemicals, 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 the hexazinone 

registration review. 
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Registration Review for Hexazinone– Projected 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 and Begin Post-Decision Follow-up 2016 

Total (years) 6 

Guidance for Commenters

The public is invited to comment on EPA’s preliminary registration review work plan and 

rationale. The Agency will carefully consider all comments as well as any additional 

information or data provided in a timely manner prior to issuing a final work plan for the 

hexazinone case. 

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. Growers and 

other stakeholders are asked to comment on any trade irritant issues resulting from lack of 

Maximum Residue Levels (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

Hexazinone is not identified as a cause of impairment 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_detail?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 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 
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Management Process (see: 

http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm) 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 hexazinone, compared to the general population. Please 

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

exposure compared to the general population. 

Other Information

Stakeholders are also specifically asked to provide information and data that will assist the 

Agency in refining the risk assessments, including 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 related to mass per unit area of treatment zone 

e. frequency of application, application 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 90th percentile reported use rates from usage data – national, state, and 

county. 

5. Application timing (date of first 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 90th percentile number of applications – county 

c. total pounds per year – county 

d. the year the pesticide was last used 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. 
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11. Ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian and 

mammalian mortalities) not already 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. 
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II. FACT SHEET

 

Background Information:

• Hexazinone Registration Review 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 document (RED) for hexazinone was signed in 

September 1994. The RED concluded that registered pesticide products containing 

hexazinone did not pose unreasonable 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), Chemical 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 herbicide to control a number of weeds and, 

grasses, and some woody plants in agricultural and non-agricultural areas. While there 

are no registered residential uses of hexazinone, it is applied to commercial turf that 

could be used in residential areas. 

• According to data averaged from the United States 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 data are not available for non-agricultural use 

sites, which would include use in reforestation. 

Recent Actions:

• The Agency has conducted a risk assessment that 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 effects to the CRLF. The Agency concluded 

that hexazinone will not present a direct effect 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: 
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• An environmental fate and effects risk assessment for hexazinone was completed in 

support of the 1994 RED. It noted ecological 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, including 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 Scoping 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 most recent human health risk assessment for 

hexazinone. A summary follows: 

Hazard Characterization: 

• In acute toxicity studies, hexazinone is Toxicity Category III via the oral exposure route 

and Toxicity Category IV via the dermal irritation, acute dermal, and inhalation routes of 

exposure. Hexazinone is Toxicity Category I via the eye irritation route 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 all population subgroups. 

Residential: 

• The 1994 RED did not assess residential scenarios 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 this use in residential 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 rely in part on data from human studies 

comprising 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 in these multi-pesticide generic exposure databases, and on the 

basis of available evidence has found them to have been neither fundamentally unethical 

nor significantly deficient relative to standards of ethical research conduct prevailing 

when they were conducted. There is no regulatory barrier to continued reliance on these 
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studies, and all applicable requirements of EPA’s Rule for the Protection of Human 

Subjects of Research (40 CFR Part 26) have been satisfied. 

Cumulative: 

• While hexazinone is a triazine herbicide, the preliminary evaluation of common 

mechanisms of toxicity indicated that hexazinone does not have a common mechanism of 

toxicity sufficient to be grouped with the triazines for a cumulative assessment. 

Therefore, hexazinone has not been included in any cumulative assessment. 

Incidents:

Ecological: 

• There were nine incident reports for hexazinone in the Agency’s Ecological Incident 

Information System (EIIS). All reported incidents were associated with non-target 

exposure to terrestrial plants.

Human: 

• The OPP Incident Database System (IDS) was 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 health and environmental agencies and individual 

consumers. This search indicates that eight incidents were reported. However, upon 

review, only two were identified as definite, probable, or possible cases involving 

hexazinone exposure. 

Data Call-In Status:

• A Data Call-In (DCI) was issued 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 appropriately 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 Pesticide Product Label System (PPLS) website: 

http://oaspub.epa.gov/pestlabl/ppls.home.