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hexazinone (Velpar) Herbicide Profile 9/88

Name of Chemical:  Hexazinone
Reason for Issuance:  Registration Standard
Date Issued:  September 1988
Fact Sheet Number:  183
                    1. DESCRIPTION OF CHEMICAL
- Generic Name:  3-cyclohexyl-6-dimethylamino-1-methyl-1,3,5-triazine-
- Common Name:  Hexazinone
- Trade Name:  Velpar
- EPA Shaughnessy Code:  51235-04-02
- Chemical Abstracts Service (CAS) Number:  107201
- Year of Initial Registration:  1975
- Pesticide Type:  Herbicide
- Chemical Family:  Triazine
- U.S. Producer:  Dupont
- Registered Uses:  Terrestrial food crop use on fruit, sugarcane,
  alfalfa,- pastures/rangeland and fallowland;
- Terrestrial nonfood crop use on grasses, rights-of-ways, and other
  noncrop areas:
- Aquatic nonfood crop uses on drainage ditch banks;
- Forestry use on Christmas tree plantation, conifer release, and
  conifer forest plantings.
- Predominant Uses:   A selective herbicide used to control grasses and
  broadleaf and woody plants.  Approximately 33% is used on alfalfa, 31%
  in forestry, 29% in industrial areas, 4% on rangeland and pastures,
  and < 2% on sugarcane.
- Formulation Types Registered:  Technical, formulation intermediate,
  granular, pelleted/tableted, dry flowable, emulsifiable concentrate,
  soluble concentrate/liquid, and ready-to-use liquid.
- Methods of Application:  Postemergence, preemergence, layby, directed
  spray, or basal soil treatment using ground equipment or where
  appropriate, broadcasted using aerial equipment.
- Rates of Application:  lb ai/A = pounds active ingredient per acre
              Terrestrial food crop -    0.22 -  6.0 lb ai/A
              Terrestrial nonfood crop - 0.67 - 13.5 lb ai/A
              Aquatic nonfood crop -     1.0 -  13.5 lb ai/A
 .            Forestry -                 0.45 - 6.0 lb ai/A
                      3. SCIENCE FINDINGS
Chemical Characteristics:
- Physical State:  crystalline solid
- Color:  white
- Melting point:  115-117 degrees C
- Solubility:  soluble in water, chloroform, methanol, benzene,
  dimethylformamide, acetone, toluene, and hexane.
- Vapor Pressure:  2 x 10 minus 7 mmHg, 25 degrees C.
- Stability:  Stable in aqueous solutions at pH 5, 7, 9 at temperatures
  up to 37 degrees C.
Toxicology Characteristics:
- Acute Toxicity:
  - Oral (rat):  1690 mg/kg (males), toxicity category III.
    Testing of females is required.
  - Dermal (rabbit):  > 5278 mg/kg (males), toxicity category IV.
    If a gender difference is exhibited in the acute oral test on
    females, testing on females may be required.
  - Inhalation (rat):  7.48 mg/l (males), toxicity category III.
    If a gender difference is exhibited in the acute oral test on
    females, testing on females may be required.
  - Primary Eye Irritation (rabbit):  Corrosive, causing irreversible
    eye damage, toxicity category I.
  - Primary Dermal Irritation:  Not an irritant.
- Subacute Toxicity:
  - A 21-day dermal study is required.  Two acceptable oral toxicity
    studies were reviewed and no additional data are required.  In the
    90-day dog study, at the Lowest Effect Level (LEL) cf 125 mg/kg
    (highest dose tested (HDT)), there was decreased body weight in both
    sexes, increased alkaline phosphatase in both sexes, decreased
    albumin /globulin values in both sexes, and increased absolute and
    relative liver weight in both sexes.  There were no compound-related
    histopathological effects.   The No Observed Effect Level (NOEL) was
    25 mg/kg.
  - In the 90-day rat study, at the LEL of 250 mg/kg (HDT), there was
    decreased body weight in both sexes.  There were no compound-related
    effects in mortality, toxic signs, food consumption, clinical
    pathology, organ weights, and histopathology.  The NOEL was 50
- Chronic Toxicity:
  - Chronic Oral Toxicity
    - One acceptable chronic feeding study in rats has been submitted.
      A data gap exists for a chronic nonrodent (dog) feeding study.
    - In the rat study, there was increased survival over all test
      groups for male rats at 125 mg/kg at 2 years.  Survival  at 2
      years in female rats was comparable between control  and treated
      groups.  The systemic NOEL was 10 mg/kg.  At the LEL of 50 mg/kg,
      females had a 5% decreased body  weight and slight decrease in
      food efficiency.  At 125  mg/kg, there were significant toxic
      effects in both  sexes.  Males had a 12% body weight decrease, a
      4%  food consumption decrease, increased white blood cells  and
      eosinophiles, alkaline urine and organ weight changes.  Females
      had a 19% body weight decrease, slight food  efficiency decrease,
      alkaline urine and organ weight changes.
    - Oncogencity:  Mouse study - The oncogenic potential is incon-
      clusive due to a possible ambiguity in the classification of liver
      neoplasia in both sexes.  The systemic NOEL is 30 mg/kg.  The
      liver slides must be rereviewed by the Agency.
    - Rat Study - There were no oncogenic effects up to and
      including 125 mg/kg (HDT).
    - The Agency will reassess hexazinone's oncogenic potential
      after rereview of the mouse study.
    - Teratoloqy: Rat study - At 900 mg/kg/day (HDT), developmental
      toxicity was evidenced by decreased fetal body weight, and partial
      ossification, kidney anomalies, and misaligned sternebrae.  The
      LEL was 400 mg/kg and the NOEL was 100 mg/kg/day for
      developmental.  For maternal toxicity, the NOEL was 100 mg/kg/day.
    - Rabbit study - NOEL for developmental and maternal
      toxicity was 50 mg/kg/day.
    - The Agency has determined that hexazinone is not a teratogen.
    - Reproduction: The Agency is requiring that additional information
      be submitted on a rat study that exhibited a NOEL of 50 mg/kg.
- Mutagenicity:
  Not a mutagen in a gene mutation, an unscheduled DNA synthesis or in a
  chromosomal aberration study in rats. However, a chromosomal
  aberration study with the Chinese hamster showed a positive response.
  The Agency has determined that hexazinone is not a mutagenic agent.
- Metabolism:
- The Agency has reviewed one acceptable rat metabolism study.  C14 was
  excreted as an average of 97% of the total dosed radioactivity via the
  urine (ca. 77%) and feces (ca. 20%) during the collection period.  The
  results were comparable for each treatment regimen.  Very low levels
  of radioactivity were detected in the GI tract, hide, excised organs,
  muscle, blood, and fat.  Hexazinone was metabolized primarily by
  hydroxylation and demethyl- ation resulting in eight major
  metabolites.  No additional data are required.
- Major Routes of Exposure:
  - The major routes of exposure are dermal and occular during mixing,
    loading, and application.
Physiological and Behavioral Characteristics:
- Foliar Absorption:  Hexazinone is absorbed through the roots and/or
  leaves depending upon the type of formulation and method of
- Translocation:  Following root absorption, hexazinone translocates
  upward through the xylem.
- Mechanism of Pesticide Action:  Hexazinone acts as photosynthesis
Environmental Characteristics:
- Persistence in Water:  Hexazinone is persistent in water at pH 5,7,
  and 9.
- Mobility in soil:  Hexazinone is mobile in soil.
- Bioaccumulation:  Hexazinone does not accumulate in fish.
- Environmental Fate and Groundwater:
  - Contamination Concerns:  Hexazinone belongs to the triazine family
    of pesticides.  Some of these pesticides have been found in ground
    water. Because hexazinone has been identified as being persistent in
    water and mobile in soils, there is concern for groundwater
    contamination.  Data are required to address this concern.
  - Nontarget Organisms:  The Agency is requiring Droplet Spectrum and
   .Spray Drift Evaluation tests because of the phytotoxicity of
    hexazinone, its aerial method of application, and the potential
    exposure of off-site plants to the pesticide.
- Exposure of Humans:
- Hexazinone has not been reported to be associated with any death or
  hospitalized cases since 1976. The voluntary accident reporting system
  reported one accidental ingestion.
- Technical grade hexazinone is corrosive to the eye and causes
  irreversible eye damage.  Use of protective goggles, face shield, or
  safety glasses are required for mixers, loaders, and applicators.
- Exposure during Reentry Operations:  The Agency has not received
  adequate toxicological or epidemiological evidence to indicate that
  residues of hexazinone can cause adverse effects on persons entering
  treated sites.  No reentry data are required and no reentry interval
  has been imposed.
Ecological Characteristics
- LD = lethal dose
- LC = lethal concentration
- EC = effect concentration
- Avian Toxicity:  Acceptable data indicate that technical hexazinone is
  practically nontoxic to birds.
- Acute oral (Bobwhite) LD50 = 2258 mg/kg
- Dietary Toxicity (Mallard) LC50 = >10,000 ppm
                   (Bobwhite) LC50 = >5,000 ppm
- Fish Toxicity:  Acceptable data indicate that technical hexazinone is
  practically nontoxic to fish.
- Fish Acute (Rainbow trout) LC50 = >320 ppm
             (Bluegill sunfish) LC50 = >370 ppm
             (Fathead minnow) LC50 = >274 ppm
             (Bluegill sunfish) LC50 = >505 ppm
- Freshwater Invertebrate Toxicity:  Acceptable data indicate that
  technical hexazinone is practically nontoxic to freshwater
              Daphnia magna   EC50 = 145.3 ppm
- Estuarine and Marine Organisms Toxicity:  Acceptable data
  indicate that hexazinone is practically nontoxic to
  molluscs and slightly toxic to crustaceans.
          Oyster 48-hr EC50 = >320 pm
          Shrimp 96-hr LC50 = 78 ppm
          Crab   96-hr LC50 = >1000 ppm
- Nontarget Insects:  There is insufficient information to determine
  that use patterns of hexazinone are nontoxic to honeybees.  Therefore
  a honey bee acute study is required.
- Potential Problems Related to Endangered Species:  Because of the
  aerial use pattern of hexazinone on forests and/or rangelands, there
  is a threat to endangered plant species around these use sites.
Tolerance Assessment:
- Tolerances Established:  Tolerance regulations have been established
  for residues of hexazinone and its metabolites in a variety of
  commodities (refer to 40 CFR 180.396).
- Results of Tolerance Assessment:  The nature of the residue in plants
  is adequately understood.  However, the metabolism of hexazinone in
  animals is not. Studies characterizing the total terminal residue of
  hexazinone in ruminants and poultry are required. Storage stability
  data and analysis of hexazinone residues on certain crops must be
  submitted. Additional residue analytical data are required. Processing
  data are needed for certain commodities. PHI's must also be
  established for some commodities. The adequacy of the established
  tolerances will be reassessed when the required data is reviewed.
- Hexazinone does not meet any of the criteria specified in 40 CFR
  154.7; therefore a Special Review is not being initiated at this time.
- The Agency will not require restricted use classification for
  hexazinone end-use products.
- The Agency is not classifying hexazinone as an oncogen pending
  rereview of certain data from previously submitted studies.
- Additional data are needed to thoroughly evaluate the potential of
  hexazinone to contaminate groundwater.
- The Agency is requiring that a tolerance for pasture/rangeland hay be
  proposed so that the impractical restriction against the cutting of
  hay from these sites be removed from the label.
- The Agency is requiring that the tolerance for alfalfa hay be revised
  so that the impractical feeding restriction of alfalfa hay be removed
  from the label.
- EPA is developing a program to reduce or eliminate exposure to
  endangered plant species from the use of hexazinone to a point where
  use does not result in jeopardy and will issue notice of any labeling
  revisions when the program is developed.  Endangered species labeling
  is not required at this time.
- While the data gaps are being filled, currently registered
  manufacturing-use products and end-use products containing hexazinone
  as the sole active ingredient may be sold, distributed, formulated,
  and used in the United States, subject to the terms and conditions
  specified in this Standard.  Registrants must provide or agree to
  develop additional data, required in the Registration Standard.
- The following pesticide disposal statement must appear on hexazinone
  manufacturing-use products:
     "Do not discharge effluent containing this product into
      lakes, streams, ponds, estuaries, oceans, or public
      waters unless this product is specifically identified
      and addressed in an NPDES permit.  Do not discharge
      effluent containing this product to sewer systems without
      previously notifying the sewage treatment plant authority.
      For guidance, contact your State Water Board or Regional
      Office of the EPA."
- The Following Must Appear on End-Use Products:
  - In the Precautionary Statements:
     "Corrosive, causes irreversible eye damage.  Harmful if
      swallowed.  Do not get in eyes or clothing.  Mixers,
      loaders, and applicators must wear goggles, face shield,
      or safety glasses.  Wash thoroughly with soap and water
      after handling.  Remove contaminated clothing and wash
      before reuse."
- Environmental Hazard Statement:
     "Do not apply directly to water or wetlands (swamps,
      bogs, marshes, and potholes).  Do not contaminate water
      when disposing of equipment washwaters."
- In the Directions for Use Section:
     "Do not enter or allow entry into treated areas until
      sprays have dried to perform hand tasks.  A person may
      enter the areas to perform other tasks only if the
      person is wearing the personal protective eye equipment
      listed on the label."
- As appropriate, the following grazing statements should appear on the
  - For sugarcane: "Do not feed sugarcane forage to live.stock."
  - For conifer release and forest plantings (reforestation site
    preparation):  "Do not graze domestic animals on treated areas
    within 30 days after treatment."
                    6. SUMMARY OF MAJOR DATA GAPS
- The following data are required for hexazinone.  Specific requirements
  are detailed in the Data Tables, Appendix I of the Hexazinone
  Registration Standard, which can be obtained from National Technical
  Information Service (NTIS) in Springfield, Virginia.
      Study                               Due Date - From Date
                                              of Standard
Product Chemistry                             6 - 15 Months
Residue Chemistry                            18 - 24 Months
     Metabolism Studies
     Analytical methodology
     Magnitude of the Residue
     Storage Stability
Toxicology                                    9 - 50 Months
     Acute Oral
     Dermal Sensitization
     Subchronic 21 day Dermal
     Chronic Toxicity
Ecological Effects                            9 - 18 Months
     Avian Reproduction
     Freshwater Fish LC50
     Fish Early Life Stage
     Freshwater Invertebrate Acute EC50
     Aquatic Invertebrate Life-Cycle
     Honey bee Acute Contact LD50
Environmental Fate                             9 - 50 Months
     Metabolism Studies
     Mobility Studies
     Soil Dissipation Studies
     Accumulation Studies (Irrigated crop and Rotational Crops)
     Spray Drift
     Groundwater Studies
                       7. CONTACT PERSON AT EPA:
Mr. Richard Mountfort
Product Manager (Team 23)
Fungicide-Herbicide Branch
Registration Division (TS-767C)
Office of Pesticide Programs, EPA
Washington, DC  20460
Telephone:  (703) 557-1830