United Stales Office of Pesticides
Environmental Protection and Toxic Substances
Agency (H7501C)
540/FS-91-123
&EPA Pesticide
Fact Sheet
Name Of Chemical: Tribenuron Methyl
Reason for Issuance: New chemical
Date Issued: June so, 1989
Fact Sheet Number: 219
Description of Chemical
Chemical Name: Methyl 2-[[[[N-(4-methoxy-6-methyl-
1,3,5-triazin-2-yl)-
methylaminolcarbonyl]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.
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
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Science Finding
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
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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: Ci5Hi?N5 Og S
Color: Off White
Physical State: White crystalline Solid
Odor: Slightly Pungent
t
Melting Point: 141°C
Density: 1.54 g/cc
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Solubility:
Vapor Pressure:
Dissociation
Constant pKa:
PH:
Stability:
* solubility limits in organic solvents at 25«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«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«C (pH-5.0 buffer); 2.04 g/L @
20«C (pH-7.0 buffer); *18.3 g/L @ 20"C (pH-
9.0 buffer).
4.0 x 10 inillimeter Of Mercury
pKa value = 4.7
4.27 (slurry in water)
Relatively unstable in most solvents,
especially aqueous solvents. Stable to
metals. Relatively stable to sunlight
Octanol/Water Partition
Coefficient: 0.30 @ pH - 7.0
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
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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 0; Toxicity Category IV
Acute Inhalation - Rat: Waived because of granule size
Dermal Sensitization - Guinea Pig: Not a sensitizer
Subchronic Toxicitv
Data are available to satisfy the requirements for subchronic
feeding studies. These data are discussed below.
Subchronic Toxicitv
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 90-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 [HOT]).
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 oncogenity study in Charles River Crl:CD-l (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 30 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
(HOT), 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.
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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 toxicitv 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 consump-
tion 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).
Mutagenicitv; 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; struc-
tural 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. Half-
life 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.
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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-l,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.
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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
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considered supplemental and new studies have been required to
fully assess the leaching potential of EXPRESS.
Bioaccuitmlation 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 < 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 LDso>2250 mg/kg;
Avian Acute Dietary Toxicity: Mallard Duck LDso> 5620 ppm and
Bobwhite Quail > 5620 ppm;
Freshwater Fish Acute Toxicity: Bluegill Sunfish LCso> 1000 ppm
and Rainbow Trout LCso> 1000 ppm; and Freshwater Invertebrate
Toxicity: Daphnia magna LC5Q720ppm.
Based on the above data, Express is practically nontoxic to birds
on an acute and dietary basis, practically nontoxic to both warm-
water 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
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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-l/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.
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
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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.
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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.
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Tnited States
Environmental Protection Agencv
Office of Pesticide Program"(H75CHC)
PMSD, Information Services Branch
401 M Street. SW
Washington. DC 20460
OffiC'al Business
Penalty for Private Use S300
First-Class
Postage and Fees Paid
EPA
Permit No G-35
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