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540/FS-89-038
<&EPA Pesticide
Fact Sheet
Name of Chemical:
Reason for Issuance: imazethapyr
Date Issued: New Chemical Registration
Fact Sheet Number: 196
1 • Description of Chemical
Comron Name: Imazethapyr
Chemical Name: (+)-2-[4,5-dihydro—4-methyl-4-( 1-methylethyl)-5-oxo-
lH-imidazol-2-yl]-5-ethyl-3-pyridinecarboxylic acid
Trade Name: Pursuit®
OPP (Shaughnessy) No.: 128982
Chemical Abstracts Services (CAS) Number:
Enpirical Foraula: C15H22N4O3
Molecular Weight: 306.4
Year of Initial Registration: 1989
Pesticide Type: Herbicide
U.S. Producer: American Cyanamid Corpany
2. Use Patterns and Formulations
Application Sites: Terrestrial food crops
Major Crops Treated: Soybeans
Types and Methods of Application: Foliar or soil, applied broadcast
try ground equipment for control of broadleaf weeds and grasses.
Applied early preplant, preplant incorporated, preemergence, or
early postemergence.
%
Application Rate: 0.0625 jourvis active ingredient/acre (lb ai/A) or
4 ounces product/A.
Type of Formulations: Erlulsifiable concentrate.
Usual Carriers: Water with crop oil or a nonionic surfactant.
3. Science Findings
Summary Science Statement: .All data are acceptable. Inozethapyr has
lcw'acute toxicity (Category III) for acute dermal, primary eye
irritation, and acute inhalation and is less toxic (Category IV)
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for acute oral toxicity and primary dermal irritation. Imazethapyr
is not considered a skin sensitizer. Data does not show imazethapyr
to be oncogenic in rats or mice. The <3iemical is not teratogenic
in rats or rabbits, and did not produce any reproductive effects
in rats. Imazethapyr is not considered Mutagenic except at levels
toxic to cells.
Imazethapyr is practically nontoxic to birds, fish, aquatic
vertebrates, and honey bees.
Imazethapyr is persistent regardless of soil type, agricultural
practices, and climatic effects but does not appear to leach under
nontal soybean agricultural practices.
The nature of the residue in plants and aninals is
adequately understood and adequate methodology is available for
enforcement of the tolerance in soybeans.
Chemical Characteristicss
Technical
Riysical States Solid
Colors Off-vtfiite to tan
Odors Pungent
Boiling Point: N/A
Density: 0.396 g/mL untapped, 0.459 g/mL tapped
Solubility: «
Solubility at 25 *C
Solvent (g/100 mL Solvent)
Acetone 4.82
Dimethyl sulfoxide 42.25
Heptane 0.09
Methanol 10.50
Methylene chloride 18.48
2-Propanol 1.73
Toluene 0.50
Water (distilled) 0.14
Vapor Pressure: (pure form) < 1 x 10~7 mm Hg at 60 *C
Dissociation Constants pka = 3.9
pH: 2.85 at 25 *C
Toxicology Qraracteristicss
Acute Toxicology - Technical
o Acute Oral Toxicity - Rat: > 5000 mg/kg/day (male and females)
Toxicity Category IV
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o Acute Dermal Toxicity - Rabbit: > 5000 mgAg/day (males and
females) Toxicity Category III
o Primary Dermal Irritation - Rabbit: Imazethapyr is minimally
irritating. Toxicity Category IV
o Primary Eye Irritation: Imazethapyr is practically ncnirritating.
Toxicity Category III
o Dermal Sensitization - Guinea Pig: Imazethapyr is not a
dermal sensitizer
o Acute Inhalation: > 3.27 mg/L air (analytical) or 4.21 mg/L
air (gravimetric). Toxicity Category III
Acute Toxicology - Pursuit Herbicide (22.6% Formulation)
o Acute Oral Toxicity - Rat: > 5000 mgAg (males and females)
Toxicity Category IV
o Acute Denial Toxicity - Rabbit: > 5000 mgAg (males and
females) Toxicity Category IV
o Primary Eye Irritation - Rabbit: minimally irritating
Toxicity Category IV
o Primaiy Dermal Irritation: Minimally irritating
Toxicity Category IV
Acute Toxicology - Pursuit Plus (2.39% Bormulation)
¦ ¦ - I, - - - -
o Acute Oral Toxicity - Rat: > 5000 mgAg (males and females)
Toxicity Category IV
o Acute Dermal Toxicity - Rats: > 2000 mgAg (nales and females)
Toxicity Category III
o Acute Inhalation Toxicity - IC50 (males and females) 1.29 mg /
imazethapyr and 1.27 mg/pendimethalin. Toxicity Category III
o Primary Eye Irritation - Rabbits: Slight irritation at 24 hours
Toxicity Category III
o Primary Dermal Irritation - Rabbits: No erythema or edema
observed. Toxicity Category IV
o Dermal Sensitization - Guinea Pig: not a sensitizer
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Subchrcnic Tbxicity
Data are available to satisfy the requirements for sub chronic feeding
studies. These data are discussed below.
A 90-day rat subchrcnic feeding study conducted at dose levels of 0,
1000, 5000, and 10,000 parts per million (ppm) (0, 50, 250, and
500 mlligrams/kilogram [mg/kg]/day) resulted in a no-observable
effect level (NOEL) of 500 mg/kg/day (highest does tested [HOT]).
A 90-day dog subchranic feeding study conducted at dosages of
0, 1000, 5000, and 10,000 ppm (0, 25, 125, and 250 mgAg/day)
resulted in a NOEL of 250 mgAg/day (HOT).
A 21-day rabbit dermal study conducted at dosages of 0, 250, 500, and
1000 mg/kg/day resulted in a NOEL of 1000 mg/kg/day (HOT).
Chronic Feeding and (fricogenicity Studies
Data are available to satisfy the requirements for chronic feeding
studies and oncogenicity studies in two species. These data are
discussed below.
A dog chronic feeding study conducted at dosages of 0, 1000, 5000,
and 10,000 ppm (0, 25, 125, and 250 mgAg/day) resulted in a NOEL
of 250 mg/kg/day (HOT) in sales and a NOEL for females of 25
mgAg/day. The lowest-observed-effeet level (LOEL) of 125 mgAg
for females was based on decreased packed cell volume hemoglobin
and erythrocytes at 250 mgAg/day.
A 2-year rat chronic feeding/onoogenicity study conducted at dosages
of 0, 1000, 5000, and 10,000 ppro (0, 50, 200, and 500 mgAg) with
no oncogenic effects observed up to 500 mgAg/day (HOT). This
study is acceptable as a chronic feeding study with a M0EL of 500
mgAg/day (HOT) but is classified as Supplemental for an oncogenic
study because the maximum tolerated dose (MTD) was not reached (no
significant toxic effects at the HOT). A repeat of this study is
not required at this time because 1) 500 mg/kg (10,000 ppm) is
within 50 percent of the limit dose for an adequately conducted
oncogenicity study an a chemical of low toxicity; 2) this pesticide
is closely related to two other pesticides ("Scepter" and "Assert")
which tested negatively in oncogenicity testing; and 3) there were
no positive mutagenicity studies for any of the three pesticides
except for "Pursuit," which had a positive result in the in vitro
cytogenetics study, but only at levels that were toxic to the
cells.
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A 78-week mouse oncogenicity feeding study conducted at dosages of 0,
1000, 5000, area 10,000 ppm (0, 50, 750, and 1500 ngAg/day) produced
no oncogenic effects up to 1500 mgAg/day (HOT). The systemic
NOEL was 750 mg/kg/day based on decreased body weight gains in
both sexes.
Justification that the highest dose level tested in the rat chronic
feeding/onoogenicity study (1500 ng/kg) is sufficient or a new
study with an WD will be required for before additional crop
tolerances or registrations can be issued.
Teratogenicity and Reproduction
Data are available to satisfy the requirements for a 2-generation
reproduction study and teratology studies in two species. These
studies are discussed below.
A rat teratology study conducted at dosages of 0, 125, 375, or 1125
mg/kg/day demonstrated an NOEL for developmental toxicity of 1125
it*3/kg/day (HOT). The NOEL for maternal toxicity was 375 mg/kg/day
and the LOE1 was 1125 mg/kg/day (HOT).
A rabbit teratology study was calculated at dosages of 0, 100, 300,
or 1000 mgAg/day showed no teratogenic effects observed. The
NOEL for maternal toxicity was 300 mg/kg/day and the NOEL for
developmental (eribryo/fetotoxicity was 1000 mg/kg/day (HOT)).
A 2-generation rat reproduction study conducted at dosages of 0»
1000, 5000, and 10,000 ppm (0, 50, 200, and 500 mgAg). The
systemic and reproductive NOEL was 500 mg/kg/day. The study is
classified as supplementary because the dose levels were not
high enouc£i. A repeat study is not required because it would not
likely provide any useful information since the chronic dog
study would still be the preferred study.
Mutagenicity
Acceptable data are available for imazethapyr to satisfy the
mutagenicity data requirements. These data are discussed below.
Data available to evaluate the potential of imazethapyr to induce gene
mutations include reverse mutation assays in S. typhimiriuin and E.
coli, both plate and disc tests. Imazethapyr did not induce gene
mutation in either system up to 5000 micrograms (ug)/plate or 1000
ug per disc. Imazethapyr was also tested in a Chinese Hamster
Ovary (CH0) cell gene mutation assay (HGPRT locus) up to the limit
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of solubility with activation (3333 ug/mL) arid beyond the limit of
solubility without activation (4000 ug/mL). Imazethapyr did not
induce gene nutation in this system.
Imazethapyr did not result in a significant increase in chromosomal
aberrations in rat bone marrow when tested in an acute in vivo
cytogenics assay at dose levels of 0.25, 0.8, and 2.5 grams {g)/kg
body weight. When tested in an in vitro cytogenics assay in (HO
cells both with and without metabolic activation at dosage levels
of 1.14, 1.71, 1.82, 2.05, and 2.25 mg/mL imazethapyr increased
chromosomal aberrations without metabolic activation at dosage
levels toxic to cells and did not increase chromosonal aberrations
with metabolic activation. Imazethapyr was also tested in a
dominant lethal rat study at dose levels of 0, 200, 1000, or 2000 mg
active ingredient (ai)Ag and did not induce dominant lethal
nutations. This study is Si^pplemental because it was questionable
whether or not dose levels were high enough for an adequate negative
study. Another study is not required because the other studies
satisfy this requirement.
Data available to evaluate the potential of imazethapyr to induce DNA
damage includes an in vitro unscheduled ENA synthesis study in
primary rat hepatocytes tested at dose levels ranging from 13 to
1333 ug/well. Under the conditions of this test, imazethapyr did
not induce unscheduled DNA synthesis in rat hepatocytes.
Metabolism
IWo rat metabolism studies were conducted. These studies do not
oonpletely characterize the absorption, excretion, retention, and
metabolism of imazethapyr. However, a repeat study is not necessary
for this use because currently available data give sufficient
evidence that most of the chemical will be eliminated via the
urine unchanged.
Physiological and Biochemical Characteristics
Translocation and absorption by plants: Absorption through both
roots and foliage and translocated rapidly to growing points.
Metabolism/persistence in animals: Eliminated through the urine
unchanged.
Environmental Characteristics
Leaching and Adsorption/Desorption: laboratory studies show
imazethapyr to be very mobile in two sand loam and two silt loam
soils. The percentage of organic matter and sand do not appear to
have an effect on the sorption of imazethapyr.
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Field dissipation tests were conducted using preplant incorporation,
pre- and postemergenoe applications. Fields were planted to
soybeans. Irrigation was not used because irrigation is not a
normal agricultural practice for soybeans. In Kentucky silt loam,
imazethapyr was detected at the 0- to 3-inch depth in all methods
of application. Half-lives of 31 days for preplant incorporated,
20 days for preemergence, and 17 days for poetemergence were
calculated. At one sanpling for both preemergence and preplant
incorporated methods of application, imazethapyr was detected at
the 3- to 6-inch depth. Imazethapyr was not detected at other
sanpling intervals in 3- to 6-inch depths or at 6- to 9- and 9- to
12-inch sajrpling depths. These plots did not indicate leaching.
In an Illinois silt loam soil, residues of imazethapyr were detected
in the 0- to 3-inch depth for all types of application. Concen-
trations of inazethapyr detected between 30 and 60 days at the 3-
to 6-inch depth and persisted until the end of the study when
inazethapyr was applied preplant incorporated. Hie half-life was
calculated to be 287 days. When applied pre- and postemergence,
imazethapyr was not detected below the 0- to 3-inch depth. The
half-life was calculated to be 120 days.
In coarse, sandy soils found in some soils in Georgia and Iowa,
movement to 12 inches was noted. Further soil dissipation studies
will be needed for future uses with agricultural practices
different from soybeans and in soil types similar to soils found in
Georgia and Iowa.
Microbial breakdown: Imazethapyr degrades slowly under aerobic (half-
life of 33 to 37 months) conditions and very slowly under
anaerobic conditions.
L06S from volatilization: None expected because of low vapor
pressure.
Degradation from photodecocrpo6ition and hydrolysis: Imazethapyr is
stable to hydrolysis at pHs 5, 7, 9 in buffered or pond water.
Imazethapyr is resistant to degradation in soil when exposed to
artificially simulated sunlight. Imazethapyr degrades when
exposed to artificially simulated sunlight with a half-life of 46
hour8.
Bioaccumulation fish: Does not bioaccumulate in fish.
Potential to contaminate groundwater: Imazethapyr is persistent and
mobile as indicated from laboratory studies. In the field,
imazethapyr consistently shows persistence, regardless of soil
type, agricultural practices, and climatic effects. In the field,
imazethapyr does not leach to the same extent in all soil types
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and under all agricultural practices. Based on field dissipation
studies performed on soils planted to soybeans under normal
agricultural practices (no irrigation) imazethapyr does not appear
to leach. Therefore, the potential to contaminate groundwater
from use on soybeans is low.
Exposure of humans to pesticides and reentry: Applicator exposure
assessment or reentry exposure are not required because lack of
significant chronic concerns and low acute toxicity (Category III
and IV) result in low exposure to humans from imazethapyr.
Based on available information, only the minimal reentry intervals
required by law should be inposed at this time: Entry into
treated fields shall not be permitted without protective clothing
until sprays have dried and dusts have settled.
Eoological Characteristics
Acceptable data are available to satisfy the requirements for an
avian single do6e acute oral toxicity on one species; two subacute
dietary toxicity studies on one species of waterfowl and one
species of upland gamebird; two 96-hour fish acute toxicity
studies on two species of freshwater fish, preferably one coldwater
species and one warranter species; a 48-hour acute toxicity study
with freshwater invertebrates; and an acute oral toxicity to honey
bees. Studies that satisfy these requirements are listed below.
o Avian Acute Toxicity: Bobwhite Quail LC50 > 2150 mgAg and
Mallard Duck LC50 > 2150 mgAg
o Avian Dietary Toxicity: Mallard Duck LC50 > 5000 mgAg and
Bobwhite Quail LC50 > 5000 mgAg
o Freshwater Fish Acute Toxicity: Channel Catfish LC50 240
mg/L, Bluegill Sunfish L/C50 420 mg/L, and Rainbow Trout
LC50 340 mg/L
o Freshwater Invertebrate Toxicity: Daphnia magna LC50 > 1000
mg/L
o Acute Contact Toxicity: Honey bee LC50 > 1000 ug/bee
Based on the above data, imazethapyr is practically nontoxic to birds
on an acute and dietary basis, practically nontoxic to both
warmwater and coldwater fish, practically nontoxic to aquatic
invertebrates, and practically nontoxic to honey bees.
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Tolerance Assessment:
The nature of the residue in plants and animals has been adequately
defined for the use on soybeans and adequate analytical methods
are available for enforcement purposes.
A tolerance is established for residues of the herbicide imazethapyr,
ammonium salt, (+)-2-£4,5-dihydro-4-methyl-4-(1-methylethyl )-S~oxo~
lH-i«idazol-2-yll-5-ethyl-3-pyridinecarboxylic acid) in or on the
raw agricultural ooomodity soybeans at 0.1 ppm.
The PADI was calculated to be 0.25 mg/kg/day. This value was based
on a NOEL of 250 103/kg/day frcrn the 90-day dog feeding study. An
uncertainty factor of 1000 was used because an MID was not obtained
in the rat chronic/ oncogenicity study.
The theoretical maximum residue contribution (TMKC) from this tolerance
is calculated to be 0.000034 mg/kg/body weight/day which occupies
approximately 0.014 percent of the PADI. There are no other
published tolerances for this chemical.
4. Smnnary of Regulatory Position and Rationale
The available data submitted to the Agency provide sufficient
information to support registration of the use on soybeans.
Therefore, the Agency has accepted the use of imazethapyr cn
soybeans.
5. Data Gaps
There are no data gape for the use of imazethapry on soybeans.
6. Contact Person at EPA
Robert J. Taylor
Product Manager (25)
Fungicide-Herbicide BrancSi
Registration Division (H7505C)
Office of Pesticide Programs
Environmental Protection Agency
401 M Street SW.
Washington, DC 20460
Office location and Telephone Nuntoer:
Room 243, Crystal Mall #2
1921 Jefferson Davis Hicftway
Arlington, VA 22202
(703) 557-1800
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 coaplete Registration Standard for
the pesticide may be obtained from the contact person listed above.
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