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Tribenuron Methyl - Chemical Profile 6/89

                            EPA Pesticide Fact Sheet
- Name of Chemical:     Tribenuron Methyl
- Reason for Issuance:  New Chemical
- Date Issued:          June 30, 1989
- Fact Sheet Number:    219

                     1. DESCRIPTION OF CHEMICAL
- Chemical Name:  Methyl 2-[[[[N-(4-methoxy-6-methyl-1,3,5-triazin-
                  2-yl)methylamino]carbonyl]amino]carbonyl]amino]sulfonyl]
                  benzoate
- Common and Other Names:  Tribenuron Methyl,L-5300
- Trade Name:  Express
- OPP (Shaughnessy) No.:  128887
- Chemical Abstracts Service (CAS) Number:  101200-48-8
- Molecular Weight:  395.40
- Year of Initial Registration:  1989
- Pesticide Type:  Herbicide
- Chemical Family:  Sulfonylurea
- U.S. and Foreign Producers:  E.I. du Pont de Nemours & Company,Inc.

                 2.  USE PATTERNS AND FORMULATIONS
- Application Sites:  Terrestrial food crops
- Major Crops Treated:  Wheat and barley
- Type and Methods of Application:  Air or Ground
- Application Rates:  0.125-0.250 or ai/acre (9-18 g ai/ha)
- Types of Formulations:  75% Dry flowable powder
- Usual Carriers:  Mix with Water

                       3. SCIENCE FINDINGS
Summary Science Statement
     Express has low acute toxicity (Category IV) for acute dermal and
acute oral toxicity.  The product is a moderate eye irritant (Category
III) and causes no skin irritation or skin sensitization.  Express is a
Group C carcinogen (possible human carcinogen) without quantification
based on the incidence of mammary gland adenocarinomas in Sprague-Dawley
strain rats.  The Agency has determined that a quantitative carcinogenic
risk assessment for this chemical is not appropriate because:  a) the
tumors were observed in one sex and one species; b) the tumors were
significantly increased only at the highest dose tested at which the
compound was clearly toxic and exceeded an adequately high dose for
assessing carcinogenic potential; c) analog beside the s-triazine show
little evidence of carcinogenic potential; d) quantification has not
been found appropriate for the s-triazine analog; and e) there is a
possible association between the induced tumors and hormonal effects at
the highest test dose; and f) there was no evidence of genetic toxicity
shown in several studies with the herbicide.
     The Scientific Advisory Panel has placed "Express" in Group D
because the only evidence for carcinogenicity was obtained with doses
that greatly exceeded the maximum tolerated dose (MTD).  The Panel noted
that the negative data obtained with male rats and mice of both sexes
and the lack of genetic toxicity also supported Category D.  The Agency
believes that the data on carcinogenicity for this chemical do not
indicate a strong likelihood that this chemical poses a significant risk
to human health.  The chemical is not a developmental toxicant in rats
or rabbits and is not considered mutagenic.
     Express is practically nontoxic to birds, fish, aquatic
invertebrates, and honey bees. The following studies are required
because Express is to be applied by air for weed control in terrestrial
food crops.
- Plant Testing
    Tier II   Seed Germination/Emergence  123-1
                   Vegetative Vigor       123-1
                Aquatic Plant Growth      123-2
- Fate Testing
  Spray Drift - droplet size spectrum  201-1
  Spray Drift - drift field evaluation  202-1
     Express is not expected to reach ground water under normal use
conditions, although the available data was considered insufficient to
fully assess the leaching potential of EXPRESS.  The following studies
are required as part of the conditional registration.
- Partially Satisfied
    Aerobic Soil Metabolism - 162-1
    Leaching and Adsorption/Desorption - 163-1
- Partially Satisfied
    Anaerobic Soil Metabolism - 162-2
    Terrestrial Field Dissipation - 164-1
- Not Satisfied
    Anaerobic Soil Metabolism - 162-2
    Terrestrial Field Dissipation - 164-1
     The nature of the residue in plants and animals is adequately
understood and adequate methodology is available for enforcement of the
tolerance in/on barley grain, wheat grain, barley straw and wheat straw.
Chemical Characteristics of the Technical Material
                    TECHNICAL
                (Tribenuron Methyl)
- Molecular Weight:  395.40
- Molecular Formula:  C15H17N5O6S
- Color:  Off White
- Physical State:  White crystalline Solid
- Odor:  Slightly Pungent
- Melting Point:  141 degrees C
- Density:  1.54 g/cc
- Solubility:  *solubility limits in organic solvents at 25 degrees C
                  (acetone) 43.8 mg/L, (acetonitrile), 54.2 mg/L g/,
               (Carbon Tetrachloride), 3.12 mg/L (Ethyl Acetate) 17.5
               mg/L, (Hexane) 0.028 mg/L (Methanol), 3.39 mg/L
               *solubility limits in water and aqueous buffer at 25
                degrees C  *28 mg/L (pH-4.0 buffer); *50 mg/L (pH-5.0
                buffer); *280 mg/L (pH-6.0 buffer); *49 mg/L @ 20 degrees
                C (pH-5.0 buffer); 2.04 g/L @ 20 degrees C (pH-7.0
                buffer); *18.3 g/L @ 20 degrees C (pH9.0 buffer).
- Vapor Pressure:  4.0 x 10 to the minus 10 millimeter Of Mercury
- Dissociation Constant pKa:  pKa value = 4.7
- pH:  4.27 (slurry in water)
- Stability:  Relatively unstable in most solvents, especially aqueous
              solvents. Stable to metals. Relatively stable to sunlight
- Octanol/Water Partition Coefficient:  0.30 @ pH - 7.0

                   4. TOXICOLOGY CHARACTERISTICS
Acute Testing
- Acute Oral Toxicity-Rat:  > 5000 milligrams/kilogram/day (mg/kg/day)
                            (males and females); Toxicity Category IV
- Acute Dermal Toxicity-Rabbit:  > 2000 mg/kg both sexes;
                                 Toxicity Category IV
- Primary Dermal Irritation-Rabbit:  Irritation cleared by 72 hours;
                                     Toxicity Category III
- Primary Eye Irritation-Rabbit:  Opacity and irritation cleared within
                                  72 hours; Toxicity Category III
- Dermal Sensitization-Guinea Pig:  Nonsensitizing
- Acute Inhalation:  > 6.7 mg/L both sexes; Toxicity Category III
Acute Studies:  Express Herbicide (75% DF Formulations):
- Acute Oral Toxicity-Rat:  5700 mg/kg for males, 4800mg/kg for females;
                            Toxicity Category IV males; III females
- Acute Dermal Toxicity-Rabbit:  > 2000 mg/kg both sexes;
                                 Toxicity Category III
- Primary Eye Irritation:  Moderately irritating; Toxicity Category III
- Primary Dermal Irritation:  Score O; Toxicity Category IV
- Acute Inhalation-Rat:  Waived because of granule size
- Dermal Sensitization-Guinea Pig:  Not a sensitizer
Subchronic Toxicity
   Data are available to satisfy the requirements for subchronic feeding
studies. These data are discussed below.
   A 90-day rat subchronic feeding study conducted at dose levels of 0,
5, 87.5, and 250 mg/kg/day with a no-observable effect level (NOEL) of 5
mg/kg/day and an lowest-observable effect level (LOEL) of 87.5 mg/kg/day
   A 9O-day dog subchronic feeding study conducted at dose levels of 0,
1.25, 12.5, and 62.5 mg/kg/day with a NOEL of > 62.5 mg/kg/day (highest
dose tested [HDT])
Chronic Feeding and Oncogenicity Studies
   Data are available to satisfy the requirements for chronic feeding
studies and oncogenicity studies in two species. These data are
discussed below.
   An 18-month oncogenicity study in Charles River Crl:CD-1 (ICR)BR
strain mice fed dosages of 0, 3,30, and 225 mg/kg/day with a NOEL of 3
mg/kg/day and an LOEL of 3 0 mg/kg/day based on decreased body weight
gain in both sexes, an increased incidence of age-related effects
(amyloidosis and thyroid inflammation in both sexes, testicular atrophy
[seminiferous degeneration and oligospermia] and mortality in males
given 225 mg/kg/day).  No carcinogenic effects were observed in the
study.
   A 2-year feeding/oncogenic study in Sprague-Dawley rats fed dosages
of 0, 1.25, 12.5, and 62.5 mg/kg/day with a statistically significant
increase in the incidence of mammary gland adenocarcinomas in treated
female rats at 62.5 mg/kg/day (HDT), a NOEL of 1.25 mg/kg/day and an
LOEL of 12.5 mg/kg/day based on reduced body weight gains in treated
males and females.
   A 1-year feeding study in dogs fed dosage levels of 0, 0.625, 6.25,
and 37.5 mg/kg/day with a NOEL of 0.625 mg/kg/day and a LOEL of 6.25
mg/kg/day (both sexes) based on elevated blood levels of bilirubin and
aspartate aminotransferase (AST), increased urinary volume and decreased
body weight gain in males, levels as well as decreased body weight gain.
Developmental Toxicity and Reproduction
   Data are available to satisfy the requirements for a two-generation
reproduction study and teratology studies in two species.  These studies
are discussed below.
   A teratology study in rats fed dosage levels of 0, 20, 125, and 500
mg/kg/day with a NOEL of 20 mg/kg/day (lowest dose tested [LDT]) for
both maternal and developmental toxicity and an LOEL of 125 mg/kg/day.
Maternal effects at the 125 and 500 mg/kg/day dose levels included
decreased body weight gain and food consumption and an increased
incidence of excess salivation; fetal effects include decreased body
weights and increased numbers of resorptions (only at the HDT).
   A teratology study in rabbits fed dosage levels of 0, 5, 20, and 80
mg/kg/day with a NOEL for maternal and developmental toxicity of 20
mg/kg/day, an LOEL for maternal and developmental toxicity of 80
mg/kg/day (HDT); maternal effects included decreased feed consumption
and an increased incidence of abortions, and fetuses had slightly
reduced body weights.
   A two-generation reproduction study in rats with a NOEL of 1.25
mg/kg/day and a LOEL of 12.5 mg/kg/day based on decreased body weight
gain; there were no reproductive or developmental effects observed at
any dose level tested (HDT of 50 mg/kg/day).
- Mutagenicity:
   Acceptable data are available for Express to satisfy the mutagenicity
data requirements.  These data are discussed below.
   A gene mutation assay in Salmonella typhimurium and Chinese hamster
ovary cells in vitro.  These assays were negative; structural
chromosomal damage, including a micronucleus test in mice and a
cytogenetics assay in rats.  Both assays were negative; an unscheduled
DNA synthesis assay in rat primary hepatocytes in vitro.  The assay was
negative for genotoxicity.
- Metabolism:
   A series of limited experiments suggested that Express is readily
absorbed by male and female rats.  The excretion half-Life at the low
dose was 26 to 33 hours.  Halflife values were similar in male and
female rats and in rats given repeated daily doses (100 parts per
million [ppm] for 21 days and 20 mg/kg on day 22).  At high single doses
(1700 to 2000 mg/kg) the excretion half-life for male rats was 51 to 54
hours, and for female rats 69 to 96 hours.
   Tissue levels of Express and its metabolites increased with dose, but
there was no concentration observed in any particular organ or tissue.
   Major metabolites included metsulfuron methyl, saccharin, and O-
dimethyl triazine amine.  The major route of excretion in rats was the
urine.
Physiological and Biochemical Characteristics:
- Translocation and Absorption by Plants:  Absorption through foliage.
- Metabolism/Persistence in Animals:  Chemical and metabolites eliminated
  through the urine.
The Scientific Advisory Panel's Recommendation:
   The Scientific Advisory Panel has recommended that "Express" be
placed in Category D on the grounds that the only evidence for
carcinogenicity was obtained with doses that greatly exceeded the MTD.
The Panel noted that the negative data obtained with male rats and mice
and the lack of positive genetic toxicity also supported Category D.
The Agency believes that the data on carcinogenicity for this chemical
do not indicate a strong likelihood that this chemical poses a
significant risk to human health.
Agency's Classification For Oncogenicity:
   Methyl 2-[[[[N-(4-methoxy-6-methyl-1,3,5-triazin-2yl) methylamino]
carbonyl]amino]sulfonyl]benzoate has been classified by the Agency into
Group C (possible human Carcinogen) because of a statistically
significant increase in the incidence of malignant tumors (mammary gland
adenocarcinomas) in female Sprague-Dawley strain rats.
   The increased incidence exceeded the historical control range.  The
Agency has determined that a quantitative carcinogenic risk assessment
for this chemical is not appropriate because:  1) The tumors were
observed only in one sex and one species; 2) the tumors were
significantly increased only at the highest dose tested at which the
compound was clearly toxic and exceeded a maximum adequately high dose
to assess carcinogenic potential; 3) structural analog show little
evidence of oncogenic potential; 4) quantification has not been found
appropriate for the s-triazine analog; 5) there is a possible
association between the induced tumors and a hormonal influence at the
high test doses; and 6) in addition, there was no evidence of genetic
toxicity shown in several studies.
Environmental Characteristics:
- Hydrolysis:
  The solubility and stability of the active ingredient increases with
  increasing pH.  The half-lives of degradation are less than 1 day at pH 5,
  3-6 days at pH 7, and 32 days at pH 9.  The hydrolytic mechanism involves
  cleavage of the sulfonylurea bridge to produce degradates that contain a
  single ring moiety:  an ester sulfonamide (which contains the phenyl moiety)
  and triazine amine (which contains the triazine moiety).  The ester
  sulfonamide can undergo further reactions depending on the pH (acid
  hydrolysis to form the acid sulfonamide and cyclization to form saccharin
  under basic conditions).
- Photodegradation in Water and on soil:
  Photodegradation is not an important degradations mechanism for EXPRESS.
- Microbial degradation:
  Under both aerobic and anaerobic conditions, the degradation of EXPRESS in
  soils appears to be dominated by an abiotic (hydrolysis) process in which
  the pH of the soil controls the breakdown of the active ingredient.
  However, there is evidence indicating that the degradates are more prone to
  biodegradation than the parent and that the degradates containing the
  triazine moiety may be more persistent than those containing the phenyl
  moiety.
- Mobility in soil:
  Parent DPX-L5300 was mobil in columns of Fargo silty clay, Sassafras loamy
  sand, Gardena silty loam, and Chopart silt loam soils, with estimated kd
  values below 0.5 for all soils.
     The degradate acid sulfonamide was also found to be mobile in these
  soils. Data is needed to assess the mobility of the triazine degradates.
- Loss from volatilization:
  Volatilization of parent pesticide from soils is expected to be minimal
  because of its low vapor pressure.
- Field Dissipation Studies:
  The available dissipation data was considered insufficient to fully assess
  the leaching potential of EXPRESS.  Data indicate that the active ingredient
  dissipated from the surface 0-5 inch soil depth with half-lives of 9 days in
  an alkaline (pH 8.3) Idaho silt loam soil and 5 days in a neutral (pH 7.3)
  Illinois silty clay loam soil.  These studies were considered supplemental
  and new studies have been required to fully assess the leaching potential of
  EXPRESS.
- Bioaccumulation in fish:
  Parent DPX-L5300 is not expected to bioaccumulate in fish because of the low
  octanol/water partition coefficient.
- Accumulation in crops:
  Parent DPX-L5300 was not detected in any plant tissue (small grains, leafy
  vegetables, root vegetable) at concentrations above the 10 ppb level-of-
  concern (detection limit less than or equal to 1 ppb) 18g
Ecological Characteristics:
   Acceptable data are available to satisfy the requirements for an
avian single dose acute oral toxicity study on one species; two subacute
dietary toxicity studies on one species of waterfowl and one species of
upland game bird; two 96-hour fish acute toxicity studies on two species
of freshwater fish, preferably one coldwater species and one warmwater
species; and a 8-hour acute toxicity study with freshwater
invertebrates.  Studies that satisfy these requirements are listed
below.
- Avian Acute Oral Toxicity:  Bobwhite Quail LD50> 2250 mg/kg;
- Avian Acute Dietary Toxicity:  Mallard Duck LD50> 5620 ppm and
  Bobwhite Quail > 5620 ppm;
- Freshwater Fish Acute Toxicity:  Bluegill Sunfish LC50 > 1000 ppm and
  Rainbow Trout LC50 > 1000 ppm; and Freshwater Invertebrate Toxicity:
  Daphnia magna LC50 720ppm.
   Based on the above data, Express is practically nontoxic to birds on
an acute and dietary basis, practically nontoxic to both warmwater and
coldwater fish, and practically nontoxic to aquatic invertebrates.
   The following studies are required because Express is to be applied
by air for weed control in terrestrial food crops.
- Plant Testing:
  Tier II   Seed Germination/Emergence   123-1
            Vegetative Vigor             123-1
            Aquatic Plant Growth         123-2
- Fate Testing:
  Spray Drift - droplet size spectrum   201-1
  Spray Drift - drift field evaluation  202-1
- Tolerance Assessment:
   The nature of the residue in plants and animals has been adequately
defined for the use on wheat and barley, and adequate analytical methods
are available for enforcement purposes.
   A tolerance is established for residue of the herbicide methyl
2[[[[N-(methoxy-6-methyl-1,3,5-triazin-2-yl)methylamino]carbonyl]amino]
sulfonyl]benzoate in or on the raw agricultural commodities wheat grain
at 0.05 ppm, wheat straw at 0.10 ppm, barley grain at 0.05 ppm, and
barley straw at 0.10 ppm.
   The acceptable daily intake (ADI) was calculated to be 0.0063
mg/kg/day.  This value was based on a NOEL of 0.625 mg/kg/day from the
1-year dog feeding study.  An uncertainty factor of 100 was used to
calculate the ADI.
   The theoretical maximum residue contribution for this tolerance is
calculated to be 0.000073 mg/kg/day.  The current action will occupy
1.16 percent of the ADI.  There are no published tolerances for this
chemical.  The pesticide is useful for the purposes of this tolerance
rule.

            5. SUMMARY OF REGULATORY POSITION AND RATIONALE
   The available data submitted to the Agency provide sufficient
information to support conditional registration of the use on wheat and
barley.  Therefore, the Agency has accepted the use of Express on wheat
grain, wheat straw, barley grain, and barley straw.
   Conditions of registration are as follows:  E.I. du Pont de Nemours &
Company, Inc. will submit these additional studies and/or information
with 27 months of the date of registration (June 30, 1989).
      Aerobic Soil Metabolism - 162-1
      Leaching and Adsorption/Desorption - 163-1
      Anaerobic Soil Metabolism - 162-2
      Terrestrial Field Dissipation - 164-1
      Spray Drift-Droplet Size Spectrum - 201-1
      Spray Drift-Drift Field Evaluation - 202-1
      Tier II Seed Germination/Emergence - 123-1
      Vegetative Vigor - 123-1
      Aquatic Plant Growth - 123-2
- Public Interest Statement:
  - Express is a low use rate sulfonylurea herbicide;
  - Express has an extremely wide postemergence application window to wheat
    and barley;
  - Express has broad-spectrum weed control activity;
  - Express has a short half-life;
  - Express is nonvolatile; and
  - Express is of low toxicity to man and animals.

                     6. CONTACT PERSON AT EPA
   Joanne I. Miller
   Acting Product Manager (23)
   Fungicide-Herbicide Branch
   Registration Division (H7505C)
   Office of Pesticide Programs
   Environmental Protection Agency
   401 M Street SW.
   Washington, DC  20460
Office Location and Telephone Number:
   Room 237, Crystal Mall #2
   1921 Jefferson Davis Highway
   Arlington, VA  22202
   Telephone:  (703) 557-1830
DISCLAIMER:  The information in this Pesticide Fact Sheet is a summary
only and is not to be used to satisfy data requirements for pesticide
registration and reregistration.  The complete Registration Standard for
the pesticide may be obtained from the contact person listed above.