Environmental Protection and Toxic Substances
5WF£-92-16e
&EPA Pesticide
Fact Sheet
!-[!-[ [4-chloro-2(trifuoromethyl)phenyl]itnino
Name Of Chemical: -2-propoxyethyl]-lH-lmidazole
Reason for Issuance: Registration of New Active Ingredient
Date Issued: 10-24-91
Fact Sheet Number: 228
DESCRIPTION Of CHEMICAL ~
Generic Name: !-[!-[[4-chloro-2-(trifluoromethyl)phenyl]imino]-
2-propoxyethyl]-IH-imidazole
Common Name: Triflumizole
Trade Name: Terraguard
EPA Shaughnessy Code: 128879
Chemical Abstracts Service (CAS) Number: 68694-11-1
Year of Initial Registration: 1991
Pesticide Type: Fungicide
U.S. and Foreign Producers: Uniroyal Chemical Company, Inc.
74 Amity Road
Bethany, CT 06525
USE PATTERNS AND FORMULATIONS
APPLICATION SITES: The manufacturing use product (MP) is for use
only in the formulation of"fungicides. The end-use product is
for use in control of Cyliridrocladium root and petiole rot on
Spathiphyllum.
TYPES OF FORMULATION: The technical grade is a white crystalline
formulation containing 97% active ingredient. The end-use
product is a wettable powder containing 50% active ingredient.
TYPES AND METHODS OF APPLICATION: The end-use product is a
protectant fungicide to be used as a soil drench, foliar spray or
through chemigation for control of diseases on ornamentals grown
in enclosed commercial structures such as greenhouses, shade
houses and interior scapes.
APPLICATION RATES: For all methods of treatment for Terraguard
(soil drench, foliar spray and/or chemigation), the pesticide is
applied at the rate of 4 to 8 oz. per 100 gallons of water. This
treatment is repeated every 2 to 4 weeks or as needed. For best
results use sufficient volume to ensure adequate soil
penetration.
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SCIENCE FINDINGS
Summary Science Statement
Available acute toxicity studies indicate that triflumizole
is in Toxicity Category I (Danger) based on the primary eye
irritation study with rabbits.
Chronic feeding/oncogenicity studies were conducted in both
the rat and mouse. The chronic feeding study in the rat suggests
that the liver is the main target organ with the ovary and kidney
as secondary target organs. Although there was an accompanying
increase in organ weights, no carcinogenic effects were seen.
In the chronic feeding study in mice, the results of blood
chemistry, organ weights and gross and histological examinations
also indicate the liver as the target organ.
Triflumizole did not induce either genotoxic effects or
chromosomal aberrations in a series of mutagenicity studies.
The teratology studies were conducted in the rabbit and rat.
In the rat studies, incidences of dilatation of the renal pelvis
and increased 14th rudimentary ribs were seen. In the rabbit, an
increase in postimplantation losses was noted.
Environmental fate data indicate that triflumizole has low
potential for leaching. Aerobic soil metabolism data indicates
that triflumizole is degraded rapidly by soil microbes to several
products of which one is C02. Hydrolysis data show that the
parent compound is quite stable at near neutral pHs and undergoes
slow hydrolysis at either mild acidic or basic conditions.
Studies also show that triflumizole has a half-life of 18 days in
sandy loam soil under laboratory conditions.
Ecological studies indicate triflumizole is practically
non-toxic to honeybees and birds. Triflumizole is categorized as
being moderately toxic to highly toxic to fish. Since this is a
minor use registration and since greenhouse applications have
been traditionally treated as indoor uses, the hazards to
nontarget species and endangered species are considered to be
minimal.
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TOXICOLOGICAL CHARACTERISTICS
LD50 2.43 g/kg males
LD50 2.05 g/kg females
Toxicity Category III
LD50 > 2000 mg/kg
Toxicity Category III
LC50 > 3.2 mg/L
Toxicity Category III
Ocular opacity;
Toxicity Category I
Negative; No
irritation observed;
Toxicity Category IV
Positive for contact
sensitization
Acute Toxicity
Acute oral toxicity in rats:
Acute dermal toxicity in rats:
Acute inhalation toxicity in rats:
Primary eye irritation in rabbit:
Primary dermal- irritation in rabbit:
Dermal sensitization in guinea pigs:
CHRONIC STUDIES
Rodent Feedina/Oncogenicity
A 2-year feeding/oncogenicity study with Sprague-Dawley rats
was conducted. Rats were fed 0, 5, 20 or 80 mg/kg/day doses of
triflumizole equivalent to 0, 100, 400 and 1600 ppm triflumizole
for 104 weeks with an interim sacrifice at 52 weeks. Numerous
organ weights, clinical chemistry and hematology parameters and
microscopic changes indicate the -main target organ is the liver,
with fatty vacuolization and periacinar hepatic hypertrophy seen
at all dose levels tested. Ovarian organ weights as well as
well-developed follicles indicate the ovary as a target. Kidney
weights were affected as well with increased cortical cysts seen
in the kidneys of mid and high dose animals. The NOEL is < 100
ppm, based on fatty vacuolization and periacinar hepatic
hypertrophy seen at all dose levels tested. An increase in tumor
incidence was not noted in any treatment groups.
A 2-year feeding/oncogenicity study with male and female
mice using dietary concentrations of 0, 100, 400 and 1600 ppm
equivalent to 0, 15, 60 and 240 mg/kg/day was conducted. There
were interim sacrifices at 26, 54, 78 and 104 weeks. Major
effects were seen in the liver at all doses tested. Clinical
chemistry changes reflecting liver toxicity included changes in
alkaline phosphatase, BUN, SCOT, SGPT and cholesterol. Absolute
and relative liver weights were increased at all time periods in
the high dose males and females and in some animals of the mid
dose groups. At sacrifice, liver changes in all dose groups
included hepatic nodules and cytoplasmic alterations. The
systemic NOEL was less than 100 ppm. Although there was a slight
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increase the incidence of lymphoma in both treated males and
females, it was judged not be compound-related.
A 3-month feeding study in rats was conducted using dietary
concentrations of 0, 20, 200 and 2000 ppm equivalent to 0, 2, 20
and 200 mg/kg/day. The NOEL was 200 ppm. The LEL was 2000 ppm
(HDT) based on slight decrease in food consumption and body
weight and changes in blood chemistry.
A 3-month feeding study with mice was conducted using
dietary concentrations of 0, 20, 200 and 2000 ppm equivalent to
0, 3, 30, 300 mg/kg/day. The NOEL was 200 ppm and the LEL was
2000 ppm based on liver effects.
A 30-day feeding study with rats was conducted using dietary
concentrations of 20, 200 and 2000 ppm equivalent to 0, 2, 20 and
200 mg/kg/day. The NOEL was 200 ppm and the LEL was 2000 ppm
based on liver changes, necrosis and fatty metamorphosis.
A 30-day feeding study with mice was conducted using dietary
concentrations of 20, 200 and 2000 ppm equivalent to 0, 3, 30 and
300 mg/kg/day. The NOEL was 200 ppm and the LEL was 2000 ppm
based on enlarged livers.
Non-Rodent Feeding Studies
A 1-year feeding study with beagle dogs using dietary
concentrations of 0, 100, 300 and 1000 ppm equivalent to 0, 2.5,
7.5 and 25 mg/kg/day was conducted. The NOEL was 300 ppm and the
LEL was 1000 ppm based on liver and blood chemistry changes.
TERATOLOGY
A teratology study using Sprague-Dawley rats was conducted
by administering levels of 0, 10, 35 and 120 mg/kg/day by gavage.
The teratogenic NOEL was > 120 mg/kg/day (HDT). The maternal
NOEL in this test was 10 mg/kg/day and maternal LEL was 35
mg/kg/day based on decreased body weight and decreased water and
food consumption. The fetotoxic NOEL was < 10 mg/kg/day (LDT)
based on dilation of renal pelvis.
A complementary study was conducted using dose levels of 0
and 3 mg/kg; the NOEL was 3 mg/kg. Another teratology study
using rats was conducted using dose levels of 0, 3, 7, and 35
mg/kg fay gavage. The maternal NOEL was 7 ing/kg. The maternal
LEL was 35 ng/kg based on reduced body weight gain and decreased
food consumption. The developmental NOEL was 7 mg/kg. The
developmental LEL was 35 mg/kg based on death and increase in
incidence of 14th rudimentary ribs and cervical ribs. The A/D
ratio was determined to be 7/7 = 1.
A teratology study was conducted in rabbits by administering
dosage rates of 0, 50, 100 and 200 mg/kg by gavage. The maternal
NOEL was 50 mg/kg. The maternal LEL was 100 mg/kg based on
decreased food consumption, body weights and orgai weights. The
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developmental NOEL was < 50 mg/kg (LDT) based on decreases in
fetal and placental body weights and 24-hour survivals. The A/D
ratio was determined to be 50/< 50 «* > l. A range finding study
was conducted in rabbits using dose rates of 0, 10, 50, 100, 200
and 300 mg/kg by gavage. The maternal NOEL was 100 mg/kg. The
maternal LEL was 200 mg/kg based on decreased body weight and
food consumption. The developmental NOEL was 100 mg/kg. The
developmental LEL was 200 mg/kg based on increased postimplanta-
tion losses.
Another teratology study was conducted in rabbits using
lower doses (0, 5, 25 and 50 mg/kg by gavage). There was no
evidence of clear maternal toxicity. The offspring showed no
adverse effects. The maternal NOEL was > 50 mg/kg and the
developmental NOEL was > 50 mg/kg/day.
REPRODUCTION
In a 2-generation rat reproduction study, dose levels of 0,
30, 70 and 170 ppm in feed were used. No parental toxicity was
observed. The parental NOEL was > 170 ppm (HOT). The
reproductive NOEL was 70 ppm. The reproductive LEL was 170 ppm
based on increased gestation lengths. The developmental NOEL was
70 ppm. The developmental LEL was 170 ppm based on reduced Fla
litter size and increased fetal incidences of hydroureter and
space between body walls and organs.
In a 3-generation rat reproduction study, dose levels of 0,
70, 170 and 420 ppm in feed resulted in a NOEI < 70 ppm (LDT)
based on increased gestation length. At 170 j.r^, there was pup
mortality. At 420 ppm, there was reduced body weight gain,
increased length of estrous cycles, reduced vaginal
cornification, extended gestation length and high pup mortality.
Another 3-generation rat reproduction study was conducted
using lower dose levels (0, 30, 70 and 170 ppm). The
reproduction NOEL was < 30 ppm based on increased gestation
lengths at all doses tested. The developmental NOEL was 70 ppm.
The developmental LEL was 170 ppm based on increased incidence of
hydroureter and space between the body wall and organs, increased
pup mortality and reduced pup weight. The parental NOEL was
> 170 ppm (HOT).
MUTAGENICITY
Triflumizole was negative for mutagenicity in the mitotic
gene conversion test, rec assay test, in vitro mouse micronucleus
test, reverse mutation in Salmonella and £. goli test and
unscheduled DNA synthesis test.
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ENVIRONMENTAL FATE
Environmental fate studies for leaching/adsorption/
desorption show that unaged [ C] triflumizole was slightly
mobile in a column (30.4 cm length) of sandy soil treated with
214 ug (1 Ib ai/A) of phenyl ring-labeled [ C] triflumizole
(radiopurity 93.4%) and leached with 63.7 column CM of distilled
water. Seventy-eight percent of the recovered radioactivity was
found in the top six inches of soil. The majority (> 81%) of the
radioactivity in each soil segment was triflumizole. This,
together with the leachate data, indicates low potential for
leaching and indicates that triflumizole should not pose a
problem in field runoff or in contamination of ground water.
Data from an aerobic soil metabolism study of UC
triflumizole in sandy loam soil indicate that triflumizole
underwent soil degradation with a half-life of 18 days. The
parent compound degraded via three degradation intermediates to
4-chloro-2-trifluoromethylaniline, which volatilized from the
soil and/or underwent further degradation to C02 by
microorganisms.
Hydrolysis studies show that phenyl-labeled [UC]
triflumizole (radiochemical purity > 99%), at 5 ppm, degraded in
sterile aqueous 0.01 M buffered solutions with half-lives of 7 to
15 days at pH 5, > 30 days at pH 7 and 3 to 17 days at pH 9 when
incubated in the dark at 25 + 1 C. The registrant-calculated
half-lives were 8 to 9 days (pH 5), 64-6 days (pH 7) and 3.9 days
(pH 9). At 30 days posttreatment, ( C] triflumizole accounted
for 73.5% of the applied radioactivity in the pH 7 solution. 4-
Chloro-alpha-alpha-alpha-trifluoro-N-2-propoxyacetyl-O-toluidine
was identified as the major degradate at all three pHs, with
maximum concentrations of 83.1% of the applied at pH 5, 20.8* at
pH 7 and 84.0% at pH 9. Material, balances ranged from 96 to 103%
during the test period.
ECOLOGICAL CHARACTERISTICS
Studies submitted show that triflumizole is practically
nontoxic to honeybees (LD50 > 160 ug per bee) and birds (LC50
> 5,620 ppm and LD50 > 2,510 ppm). Since it is unlikely that
triflumizole will come into contact with these species,
it is not expected to pose a threat to honeybees and birds
(nontarget and endangered species). Triflumizole is categorized
as being moderately toxic to highly toxic to fish. The expected
levels of triflumizole in a farm pond are not predicted to exceed
1/10 of the warmwater fish LC50 (1.2 ppm) which is the nontarget
species cutoff point. There are only two endangered fish species
in Florida. The shortnosed sturgeon (Acipenser brevinostrum) is
in Duval and Putnam Counties.
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The Okaloosa darter (Etheostoma okaloosae) is in Walton and
Okaloosa Counties. None of these four counties is in southern
Florida where the pesticide will be used. The expected levels of
triflumizole in a farm pond are not predicted to exceed 1/20 of
the warmwater fish LC50 (1.2 ppm) which is the endangered species
cutoff point. Triflumizole is not expected to L<- a threat to
endangered fish. Since this is a minor use registration ar
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