r/EPA
United States
Environmental Protection
Agency
Office of Prevention, Pesticides
and Toxic Substances
(7501C)
Pesticide
Fact Sheet
Name of Chemical: Mesosulfuron-methyl
Reason for Issuance: Conditional Registration
Date Issued: March 31, 2004
Description of Chemical
Generic Name:
Common Name:
Trade Name:
EPA Shaughnessy Code:
Year of Initial
Registration:
Pesticide Type:
Chemical Family:
U.S. Producer:
Methyl 2-[[[[(4,6-dimethoxy-2-pyrimidinyl)
amino]carbonyl]amino]sulfonyl]-4-
[[(methylsulfonyl)amino]methyl]benzoate
Mesosulfuron-methyl
Mesosulfuron-methyl Technical
122009
Chemical Abstracts
Service (CAS) Number: 208465-21-8
2004
Herbicide
Sulfonyl Urea
Bayer CropScience
Use Patterns and Formulations
Application Sites:
Types of Formulations:
Mesosulfuron-methyl is registered as a Technical product for
formulation for herbicides used on wheat.
technical product (96.8% a.i.), two end use products (2.0%
and 4.5% a.i.)
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3.
Science Findings
Summary Science Statements
The acute toxicity data indicate that mesosulfuron-methyl has low acute oral, dermal, and
inhalation toxicity. It was not found to be a skin irritant, and irritation that occurred in the eye
cleared up 48 hours after exposure. Dermal sensitization was not determined because the study was
unacceptable. There are no primary target organs identified that were associated with exposure to
mesosulfuron-methyl. Increased mucus secretion in the cardiac and fundic sections of the stomach,
and chronic superficial gastristis (1/6) were noted in the chronic toxicity study in dogs. There was
no evidence of developmental or reproductive toxicity. The data demonstrate no increased
sensitivity of rats or rabbits to in utero or early postnatal exposure to mesosulfuron-methyl. Based
on several negative in vivo and in vitro studies, it methyl has no mutagenicity potential.
Carcinogenicity studies in rats and mice did not show increased incidence of spontaneous tumor
formation. Mesosulfuron-methyl is classified as "not likely to be carcinogenic to humans". There
was no evidence of neurotoxicity in the acute, subchronic, or chronic toxicity studies.
Biotransformation is the major route of degradation of mesosulfuron in the environment, as
evidenced by mineralization (i.e., formation of CO2) in aerobic soils and persistence varying with
microbial population and temperature. In water-sediment systems, persistence is also variable,
mineralization is negligible and, like in soils, non-extractable residues increase with time.
Mesosulfuron produces degradates that have been identified for other sulfonylurea herbicides as well
as degradates that are unique to this chemical. As implied by the long replanting intervals
recommended on the labels (up to 12 months), mesosulfuron remains phytotoxic in soils long after
application.
Chemical Characteristics
Chemical Properties of Mesosulfuron-methyl Technical
Property of Technical
Color
Physical state
Odor
Stability to normal and elevated
temperatures, metals, and metal ions
Flammability
pH
Melting point/
Melting range
Result
Cream color
solid powder
weekly punaent
No significant change in the Al content
54°C. The Al was found to be stable in
sulfate over a ranae of 30-205°C.
(2.2% decrease) when stored for 14 days at
presence of Fe & Al, Al acetate and Fe
Nonflammable
5.1 25°C
189-192°C.
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Chemical Properties of Mesosulfuron-methyl Technical
Property of Technical
Relative Density
Dissociation constants in water
Partition coefficient (n-octanol/water),
shake flask method
Water solubility: column elution
method; shake flask method
Vapor pressure
Result
1 .53 gm/cc at 23 °C
pKa = 4.35 + 0.04 at 20 °C by photometric titration method
log Po/w = 1 .90 (pH, 4); 1 .39 (pH,5); -0.48 (pH,7);
-2.06(pH,9):-2.10(pH,10)
water
organic solvents
1.1 x10'11 Pascal at 25 °C.
Toxicology Characteristics
Toxicology Profile for Mesosulfuron-Methyl
Guideline No./ Study
Type
870.3100
90-Day oral toxicity
rodents
870.3100
90-Day oral toxicity
rodents
870.3150
90-Day oral toxicity in
nonrodents
870.3200
21/28-Day dermal
toxicity
870.3250
90-Day dermal toxicity
870.3465
90-Day inhalation
toxicity
870.3700a
Prenatal developmental
in rodents
Results
NOAEL = 908/977 [M/F]
LOAEL = not observed.
NOAEL = 1238.3/1603.4
LOAEL = not observed.
NOAEL = 648/ 734 [M/F]
LOAEL = not observed.
mg/kg/day
[M/F] mg/kg/day
mg/kg/day
Study not required.
Study not required.
Study not required.
Maternal NOAEL = 1000 mg/kg/day
LOAEL = not observed
Developmental NOAEL = 1000 mg/kg/day
LOAEL = not observed
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Guideline No./ Study
Type
Results
870.3700b
Prenatal developmental
in nonrodents
Maternal NOAEL = 1000 mg/kg/day
LOAEL = not observed
Developmental NOAEL = 1000 mg/kg/day
LOAEL = not observed
870.3800
Reproduction and
fertility effects
Parental/Systemic NOAEL = 1175.27 1387.6 [M/F] mg/kg/day
LOAEL = not observed
Reproductive NOAEL = 1175.27 1387.6 [M/F] mg/kg/day
LOAEL = not observed
Offspring NOAEL = 1175.27 1387.6 [M/F] mg/kg/day
LOAEL = not observed
870.4100a
Chronic toxicity
rodents
NOAEL = 764/ 952 [M/F] mg/kg/day
LOAEL = not observed.
870.4100b
Chronic toxicity dogs
NOAEL = 155 [M] mg/kg/day
LOAEL = 574 [M] mg/kg/day based on increased mucus secretion
in the cardiac and fundic sections of the stomach of the males dogs
(FIDT) and chronic superficial gastritis (1/6).
870.4200
Carcinogenicity rats
NOAEL = 764/ 952 [M/F] mg/kg/day
LOAEL = not observed.
(no) evidence of carcinogenicity
870.4300
Carcinogenicity mice
NOAEL = 1069.47 1355.6 [M/F] mg/kg/day
LOAEL = not observed.
(no) evidence of carcinogenicity
Gene Mutation
870.5100
Bacterial reverse
mutation assay
Negative ± S9 up to cytotoxic 5000 jig/ml plate
Gene Mutation
870.5300
Mammalian cell
culture
Negative ± S9 up to cytotoxic 2500 jig/ml and precipitation 250
M-g/ml
Cytogenetics
870.5395
Micronucleus test on
Negative at the highest dose tested (limit dose) 2000 mg/kg.
mouse
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Guideline No./ Study
Type
Cytogenetics
870.5375
Chromosomal
aberrations
Other Effects
870.5550
Unscheduled DNA
870.6200a
Acute neurotoxicity
screening battery
870.6200b
Sub chronic
neurotoxicity screening
battery
870.6300
Developmental
neurotoxicity
870.7485
Metabolism and
pharmacokinetics
870.7600
Dermal penetration
Special studies
Results
Negative ± S9 precipitation >100 jig/ml
Negative ± S9 precipitation >100 jig/ml
Study not required
Study not required
Study not required
Overall recovery of the radioactive dose was 98-103%,
predominantly recovered in the feces within 24 hours (80-97%
dose). The onset of absorption was quick (detected in the blood 15
minutes post-dose), but the quantity absorbed was low. At 72 hours
post-dose (or 168 hours following the final dose of the repeated
study), urinary excretion accounted for 1-4% (except 13-14% in the
10 mg/kg animals), and radioactivity in the bile of the 10 mg/kg
animals was only 7-9% dose by 12 hours post-dose. The 10 mg/kg
rats had slightly more radioactivity in urine and slightly less
radioactivity in feces compared to the 1000 mg/kg rats.
Bioaccumulation was not observed, and radioactivity in tissues was
<0.1% dose in all animals at each study termination.
100% dermal absorption factor (default value)
Study not required.
Summary of Toxicological Doses and Endpoints for Mesosulfuron methyl for Use in Human
Risk Assessment
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Exposure
Scenario
Acute Dietary:
All populations
Chronic Dietary:
All populations
Incidental Oral:
Short and
Intermediate-
Term)
Dermal Exposure:
Short, Intermediate
and Long-Term
Inhalation
Exposure: Short ,
Intermediate and
Long-Term
Cancer (oral,
dermal, inhalation)
Dose Used in
Risk
Assessment, UF
Special FQPA SF*
and Level of
Concern for Risk
Assessment
Study and Toxicological
Effects
No study in the toxicology database indicated there is an acute dietary endpoint of
concern.
NOAEL= 155
mg/kg/day
UF = 100
Chronic RfD =
1.55 mg/kg/day
FQPA SF = IX
cPAD =
chronic RfD
FQPA SF
= 1.55 mg/kg/day
Chronic oral toxicity study in dogs.
LOAEL = 574 mg/kg/day [M] based
on increased mucus secretion in the
cardiac and fundic sections of the
stomach, and chronic superficial
gastritis (1/6) of male dogs.
No Residential Uses are Proposed for Mesosulfuron-methyl.
Quantification of dermal risk is not required for this route of exposure due to the
lack of dermal, systemic, neurological, and developmental toxicity concerns.
OralNOAEL= 155
mg/kg/day
(100% Oral
Absorption Factor)
Residential LOC for
MOE = NA
Occupational LOC for
MOE = 100
Chronic oral toxicity study in dogs.
LOAEL = 574 mg/kg/day [M] based
on increased mucus secretion in the
cardiac and fundic sections of the
stomach, and chronic superficial
gastritis (1/6) of male dogs.
"Not likely to be carcinogenic to humans" based on the lack of evidence of
carcinogenicity in the rats and mice.
UF = uncertainty factor, FQPA SF = Special FQPA safety factor, NOAEL = no observed adverse effect level, LOAEL
= lowest observed adverse effect level, PAD = population adjusted dose (a = acute, c = chronic) RfD = reference dose,
MOE = margin of exposure, LOC = level of concern, NA = Not Applicable
DIETARY EXPOSURE:
Based on available data, a suitable endpoint for acute dietary risk assessment was not
identified because no effects were observed in oral toxicity studies (including developmental
studies) which could be attributed to a single-dose exposure. Therefore, mesosulfuron-
methyl is not expected to pose an acute dietary risk. For chronic dietary consumption,
exposure to mesosulfuron-methyl from food will utilize <1% of the cPAD for the U.S.
population, <1% of the cPAD for infants < 1 year old, and <1% of the cPAD for children 1-
12. In addition, there is potential for chronic dietary exposure to mesosulfuron-methyl in
drinking water. After calculating DWLOCs and comparing them to the EECs for surface
(0.15 ppb) and ground water (0.015 ppb), the aggregate exposure is not expected to exceed
100% of the cPAD. Mesosulfuron-methyl was classified as "not likely to be carcinogenic
to humans".
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EPA determined that the 10X FQPA Safety Factor to protect infants and children should be
removed. The FQPA factor is removed because i) There is no evidence of increased
quantitative/qualitative susceptibility in the available acceptable guideline studies; ii) There
are no residual uncertainties for pre- and/or post-natal toxicity; iii) Clear NO AELs have been
identified for the effects of concern; iv) No adverse effects were noted at the highest dose
tested in the acceptable guideline developmental toxicity and reproduction studies in rats,
and developmental toxicity study in rabbits; and v) There are no proposed residential uses.
NON-DIETARY EXPOSURE:
There are no residential uses for mesosulfuron-methyl that result in residential exposure to
mesosulfuron-methyl.
There is a potential for occupational exposure to mesosulfuron-methyl during mixing,
loading, application, and postapplication activities. Because no dermal endpoints were
identified by HIARC, the occupational risk assessment was based on inhalation exposure
only. Short-term and intermediate-term risks were assessed. Long-term exposures are not
expected for handlers of mesosulfuron-methyl for the proposed use pattern.
MOEs for occupational handler inhalation exposure range from 900,000 (mixer/loader: open
mixing water-dispersible granules for aerial application) to 10,000,000 (aerial application
of liquid: closed cockpit). All occupational handler MOEs are greater than HED's target
MOE of 100, and therefore, are not of concern.
RESIDUE CHEMISTRY:
EPA has established tolerances for tolerances for residues of mesosulfuron-methyl on the
raw agricultural commodities aspirated grain fractions at 0.60 ppm, meat byproducts of
cattle, goat, horse, and sheep at 0.01 ppm, wheat forage at 0.60 ppm, wheat germ at 0.10
ppm, wheat grain at 0.03 ppm, wheat hay at 0.06 ppm, and wheat straw at 0.30 ppm. There
are currently no Codex, Canadian, or Mexican MRL' s or tolerances for mesosulfuron-methyl
on wheat.
ENDANGERED SPECIES:
Endangered species Levels of Concern were exceeded for dicots in terrestrial habitats. At
least one of eight listed endangered dicot plant species is located in counties where spring
application to winter wheat is grown: Idaho (3 counties), Minnesota (5 counties), Montana
(2 counties), Oregon (9 counties), Washington (8 counties), and Wyoming (1 county). This
list was generated using a database which intersects AgCensus data (2001-2003) with
endangered dicot plant species locations by county. It was not possible, given the
constraints of a Tier 1 assessment, to analyze the spatial relationship of wheat acreage to
endangered plant habitats on a county-by-county basis. The Tier 1 assessment has been
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forwarded to FEAD for use in their endangered species assessment but FEAD has not started
their assessment. Thus, the actual likelihood of exposure of specific endangered plants in
specific counties is not known. In general, however, the high toxicity of mesosulfuron to
plants indicate that it is likely that endangered plant species may be at risk from the proposed
used of this chemical.
EPA is time limiting the registration of mesosulfuron-methyl for 2 years while the FEAD
endangered species assessment is put in place. In the interim, to avoid adverse effects on
endangered dicot species, the following mitigation measures will be imposed on the end use
product labels in Counties where endangered species occur. For ground applications, the
applicator must: 1) Apply only when there is sustained wind away from native plant
communities, 2) Leave a 25 foot (Silverado) or 50 foot (Osprey) untreated buffer between
treatment area and native plant communities, or 3) Use low pressure nozzles according to
manufacturer's specifications that produce only coarse or very coarse droplets. For aerial
applications, the applicator must: 1) Apply only when there is sustained wind away from
native plant communities, or 2) Leave a 150 foot (Silverado) or 350 foot (Osprey) untreated
buffer between treatment area and native plant communities.
ENVIRONMENTAL FATE:
Biotransformation is the major route of degradation of mesosulfuron in the environment, as
evidenced by mineralization (i.e., formation of CO2) in aerobic soils and persistence varying
with microbial population and temperature. In water-sediment systems, persistence is also
variable, mineralization is negligible, and non-extractable residues increase with time.
Mesosulfuron produces degradates that have been identified for other sulfonylurea
herbicides as well as degradates that are unique to this chemical.
Mesosulfuron exhibits weak binding to soils. Mesosulfuron, like other sulfonylurea
herbicides, will predominate in the water phase and not in sediments. It has the potential
to leach to ground water or reach surface water by runoff. Mesosulfuron has low potential
to volatilize from soil or water or to bioaccumulate in fish.
Considering the widespread, potential use areas of variable soils, microbial population and
activity, water bodies, climates/meteorology, and agricultural practices high variability in
persistence in soil and water-sediment systems is expected.
ECOLOGICAL EFFECTS:
Mesosulfuron is phytotoxic to endangered and non-endangered non-target terrestrial plants
and and plants growing in semi-aquatic habitats. It is also phytotoxic to aquatic vascular
plants. However, because the plant testing studies submitted were not performed using the
appropriate proportions of active ingredient and safener to be representative of the products
being proposed for registration, there is a large amount of uncertainty surrounding the degree
of phytotoxicity that would be exhibited under actual use conditions. The data do suggest
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that the principal risks to plants will be associated with foliar uptake (spray drift) compared
with runoff exposure (seed emergence). In the absence of representative data, the
endangered non-target terrestrial plant species spray drift assessment was performed using
the most sensitive endpoint (lettuce EC05).
A chronic reproductive effect (reduced number of live embryos to viable embryos) was
observed in mallard duck; however, the NOAEC could not be determined (effects seen at
lowest concentration tested - 38 ppm). No chronic reproductive effect was observed in the
other bird species tested (bobwhite quail).
Slightly toxic to freshwater fish (LC50 > 91.5 ppm) and freshwater aquatic invertebrates
(LC50 > 90.2 ppm). In the chronic effects study for freshwater fish, the NOAEC /LOAEC
is > 29.6 ppm, with no effects seen. In the chronic effects study for freshwater
invertebrates, the NOAEC was 1.7 ppm and the LOAEC is 3.0 ppm, with the reproductive
effects being a reduction in number of offspring/parent and body weight, and an increase in
the time to first brood release.
Practically non-toxic on an acute basis to the bobwhite quail and mallard duck (LD50 > 2,000
mg/kg), mammals (LD50 >7000 ppm), honey bee (LD50 > 13 ug/bee), and estuarine/marine
fish (LC50 > 105 ppm). Practically non-toxic to the bobwhite quail and mallard on a sub-
acute basis (LC50 > 4,750 ppm). Presumed nontoxic on a chronic basis to estuarine/marine
fish based on the high LC50s. No chronic or reproductive effects were observed in mammals
(NOAELof 1,000 ppm).
Mechanism of Pesticidal Action
Mesosulfuron-methyl belongs to the class of chemicals called sulfonyl ureas. The chemical works
by inhibiting the enzyme acetolactate synthase (ALS), which leads to depletion of key amino acids
that are necessary for protein synthesis and plant growth.
4. Summary of Regulatory Position and Rationale
Available data provide adequate information to support registration of the Mesosulfuron-methyl
technical, Osprey Herbicide, and Silverado Wild Oat herbicide for use on wheat.
5. Required Labeling
For OSPREY™ Herbicide, a preharvest interval (PHI) of 60 days for hay has been
imposed.
For SILVERADO™ Wild Oat Herbicide, only one application per growing season
at up to 0.003 Ib ai/A (2.25 oz/A) is allowed. Also, a preharvest interval (PHI) of 50
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10
days for hay has been imposed.
• A plantback interval of 30 days has been imposed for barley.
6. Summary of Data Gaps
7. Contact Person at EPA
Jim Tompkins
Product Manager 25
Herbicide Branch
Registration Division (7505C)
Office of Pesticide Programs
Environmental Protection Agency
401 M Street, SW
Washington, DC 20460
Office Location and Telephone Number
Room 239, Crystal Mall Building #2
1921 Jefferson Davis Highway
Arlington, VA 22202
(703)305-6224
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 reregi strati on.
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