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                 United States           Office of Pesticides and Toxic Substances   ^/J-o oo vo*
                 Environmental Protection      Office of Pesticide Programs (TS-766CI
                 Agency              Washington, DC  20460
oEPA      Pesticide
                 Fact Sheet
                 Name of Chemical:
                 Reason for Issuance: Registration Standard

                 Date ISSUed: September 1988
                 Fact Sheet Number:
     DESCRIPTION OF CHEMICAL

     Generic Name:  3-cyclohexyl-6-dimethylamino-l-methyl-
                   l,3,5-triazine-2,4(lH,3H)-dione

     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


     USE  PATTERNS AND FORMULATIONS

     Registered Uses:  Terrestrial  food crop use on fruit, sugarcane,
          alf-alf-a,- 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.

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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:  Ib ai/A = pounds active ingredient per acre
      Terrestrial food crop -    0.22 -  6.0 Ib ai/A
      Terrestrial nonfood crop - 0.67 - 13.5 Ib ai/A
      Aquatic nonfood crop -     1.0  - 13.5 Ib ai/A
      Forestry -                 0.45 -  6.0 Ib ai/A

SCIENCE FINDINGS

Chemical Characteristics:

      Physical State:  crystalline solid
      Color:  white
      Melting point:   115-117C
      Solubility:  soluble in water, chloroform, methanol,
      benzene, dimethylformamide, acetone,  toluene, and hexane.
      Vapor Pressure:  2 x lO"7 mmHg, 25C.
      Stability:  Stable in aqueous solutions at pH 5, 7, 9 at
      temperatures up to 37C.

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/1 (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.
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 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) of 125 mg/kq (highest dose tested
   (HOT)), 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 mg/kg.

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
   inconclusive due  to a possible ambiguity in the classif-
   ication 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.

   Teratology; Rat study - At 900 mg/kg/day (HDT), developmental
   toxicity was evidenced by decreased fetal body weight, and
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      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
      syntheses 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.  C^4 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 Gl 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 application.

      Translocation:  Following root absorption, hexazinone
           translocates upward through the xylem.

      Mechanism of Pesticide Action:  Hexazinone acts as
           photosynthesis inhibitor.


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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
           oae 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) LD5Q = 2258 mg/kg
                Dietary Toxicity (Mallard) LC50 = >10,000 ppm
                             _5_ (Bobwhite) LC50 = >5/000 ppm

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      Fish Toxicity:    Acceptable data indicate that technical
           hexazinone is practically nontoxic to fish.
                Fish Acute (Rainbow trout)  1*050 = >^20 ppm
                           (Bluegill sunfish)  LC^Q = >370 ppm
                           (Fathead minnow)  LC^g = >274 ppm
                           (Bluegill sunfish)  LC^g = >505 ppm
      Freshwater Invertebrate Toxicity:   Acceptable data indicate
           that technical hexazinone is  practically nontoxic to
           freshwater invertebrates.

                Daphnia maqna   50 = 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 EC$Q = >320 pm
                Shrimp 96-hr LCc,g = 78 ppm
                Crab   96~hr LC5Q = >1000 ppm

      Kontarget 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 plan'
           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.
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SUMMARY OF REGULATORY POSITION AND RATIONALE

     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.

STATEMENTS REQUIRED ON LABELS:

     The following pesticide disposal statement must appear
     on hexazinone manfacturing-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 .iildr^osed in an NPDES permit.  Do not discharge

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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 label:

For sugarcane: "Do not feed sugarcane forage to livestock."

For conifer release aad forest plantings (reforestation
site preparation):  "Do not graze domestic animals on
treated areas within 30 days after treatment."
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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
     Acuto Oral
     Dermal Sensitization
     Subchronic 21 day Dermal
     Chronic Toxicity
Ecological Effects                               9-18 Months
     Avian Reproduction
     Freshwater Fish LC5Q
     Fish Early Life Stage
     Freshwater Invertebrate Acute EC5Q
     Aquatic Invertebrate Life-Cycle
     Honey bee Acute Contact LDso
Environmental Fate                               9-50 Months
     Photodegradation
     Metabolism Studies
     Mobility Studies
     Soil Dissipation Studies
     Accumulation Studies (Irrigated crop and Rotational Crops)
     Spray Drift
     Groundwater Studies

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


DISCLAIMER;  The information presented in this Pesticide Fact
Sheet is  for informational purposes only and may not be used to
fulfill data requirements for pesticide registration and
reregistration.

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