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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: 115-117°C
Solubility: soluble in water, chloroform, methanol,
benzene, dimethylformamide, acetone, toluene, and hexane.
Vapor Pressure: 2 x lO"7 mmHg, 25°C.
Stability: Stable in aqueous solutions at pH 5, 7, 9 at
temperatures up to 37°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/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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vvEPA
U.S. Environmental Protection Agency
Office of Pesticide Program (TS-757C)
PMSD, Information Services Branch
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Washington, D.C. 20460
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