United States Office of Pesticides
Environmental Protection and Toxic Substances
Agency (H7501C)
: 54Q/FS-89-Q5R
vvEPA Pesticide
Fact Sheet
. beta-(4-chlorophenoxy)-alpha-(l,I-dimethylethyl
Name Of Chemical: lH-l,2,£-triazole-l-ethanol
Reason for Issuance: New Chemical Registration
Date Issued: July 1989
Fact Sheet Number: 204
DESCRIPTION OF CHEMICAL
Generic Name: beta-(4-chlorophenoxy)-alpha-(1,1-dimethylethyl)-
lH-l,2,4-triazole-l-ethanol and its metabolites
containing chlorophenoxy and triazole moieties.
Common Name: triadimenol
Trade Name: Baytan
EPA Shaughnessy Codes: 127201
Chemical Abstracts Service (CAS) Number: 5219-65-3
Year of Initial Registration: 1989
Pesticide Type: Fungicide
U.S. and Foreign Producers: Mobay Corporation
USE PATTERNS AND FORMULATIONS
APPLICATION SITES: Seeds of barley, corn, oats, rye,
sorghum and wheat to control seed- and soil-borne
diseases and to provide early season control of foliar
diseases.
METHOD OF APPLICATION: Application will be made as a water-
based slurry through standard slurry or mist type
commercial seed treatment equipment.
TYPES OF FORMULATION: 25% dry flowable end-use product
and 90% technical powder for formulating use. .
APPLICATION RATES: For barley, oats, rye and wheat, apply
0.25-0.5 oz. ai./lOO Ibs of seed; for sorghum, apply
0.5 oz. ai./lOO Ibs of seed; and for corn, apply 1.0 oz.
ai./lOO Ibs of seed.
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USUAL CARRIER: water.
SCIENCE FINDINGS
Summary Science Statement
Available acute toxicity studies indicate that triadimenol
is in toxicity category II (warning) based on an acute inhalation
toxicity study with rats.
Chronic feeding/oncogenicity studies were conducted in both
the rat and mouse. Clinical chemistry findings in the chronic
feeding study in the rat suggests that the target organ for
toxicity may be the liver. Although there was an accompaying
small increase in liver weight in the females of the high
dose group," there were no histopathologic charges in the
liver in either sex.
In the chronic feeding study in mice, the results of
blood chemistry, organ weights and gross and histological
examinations, again indicated the liver as the target organ.
Triadimenol did not induce either genotoxic effects or
chromosomal aberrations in a series of mutagenicity studies.
In addition, no strong structural activity correlation to
other carcinogens has been found.' Triadimenol was also found
not to be teratogenic in either the rat or rabbit.
Environmental fate data indicates that triadimenol is stable
to hydrolysis and appears to be stable to photolysis on the
soil surface. In addition, based on low adsorption coefficients,
triadimenol will have a low potential to leach in soil.
However, triadimenol may have a moderate potential to leach
in some Western soils.
Additional studies indicate that due to the manufacturing
process, triadimenol should have no adverse effects on non-target
organisms provided waste is disposed of properly. An overview
of the toxicity test results suggests that triadimenol is
practically non-toxic to birds, slightly toxic to fish, and
moderately toxic to aquatic invertebrates. It is also unlikely
that this registration would affect endangered species because
of its relatively low use rates, agricultural techniques
which involve drill planting of most small grains and corn,
and the low toxicity of triadimenol to all animals.
TOXICOLOGICAL CHARACTERISTICS
Acute oral toxicity in rats:
1050 689 mg/kg in males
752 mg/kg in females
Toxicity category III
Acute dermal toxicity in rats:
LE>5o >5000 mg/kg
Toxicity category III
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Acute inhalation toxicity in rats
LC5Q >1.56 mg/L
Toxicity category III
Drimary eye irritation in rabbit:
slight irritation
Primary dermal irritation in rabbit:
Toxicity category IV
Dermal sensitization in guinea pigs:
core minimum; no effect
Chronic Studies: Triadimenol has been evaluated in the following
studies.
"Rodent Feeding/Oncogenicity
1. A 2-year feeding/oncogenicity study with rats using
dietary concentrations of 0, 125, 500, and 2000 parts per
million (ppm) equivalent to 0, 6.25, 25.0, and 100 mg/kg bwt/day
in males and females. Clinical chemistry findings suggest
that the target organ for toxicity may be the liver. The
levels of SCOT and 9GPT enzymes were consistently higher at
2000 ppm in males and females when compared to controls, and
some increase in these two parameters was also observed at
500 ppm. Although there was an accompanying small increase
in liver weight in 2000 ppm females, there were no accompanying
increases in histopathologic changes of the liver in either
sex. There were only marginal effects seen on other clinical
chemistry parameters, and no effect of test compound on
clinically observed signs of toxicity, food consumption,
hematologic, or urinalysis parameters. The systemic NOEL
(no-observed effect level) is 125 ppm (6.25 mg/kg/day for
males and females) based on the increase in liver enzymes
(SCOT and SGPT). The systemic LEL (lowest effect level) was
500 ppm (25 mg/kg/day for males and for females).
2. A 2-year chronic feeding/oncogenicity study in mice
using dietary concentrations of 0, 125, 500, and 2000 ppm
(equivalent to doses of 0, 18, 72, and 285 mg/kg/day for males
and females). The results of blood chemistry, organ weights,
and gross and histological examinations indicated the liver to
be the target organ. There were time- and dose-related increases
in SAP (serum alkaline phosphatase), SCOT and SGPT activities
in both male and female animals receiving 500 and 2,000 ppm of
the test material.
In addition, increased incidence of enlarged livers,
hyperplastic nodules and increased liver weights in both
male and female animals receiving 2,000 ppm of test material
were detected at necropsy. Female animals receiving 2000 ppm
exhibited a significant increase in the incidences of liver
adenomas only, a compound-related oncogenic effect. In
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males, there were no differences in the incidences of these
lesions in treated and control males, and the incidences of
liver adenomas were similar to those observed in historical
controls.
Based on this evidence the Agency classified triadimenol
as a Category C (possible human carcinogen) in accordance
with the EPA Guidelines for Carcinogen Risk Assessment (September
24, 1986, 51 FR 33992). This evaluation was confirmed by the
Agency's Scientific Advisory Panel on December 15, 1987. How-
ever, it was also concluded that this evidence of carcinogenic!ty
did not warrant a low dose extrapolation of risks since the
tumors were only benign, were observed in only one sex, and
only at the highest dose tested. Moreover, the chemical was
negative in the genotoxic assay battery.
Based on blood chemistry findings, the systemic NOEL and
the LEL are 125 ppm and 500 ppm respectively (equivalent to
18 and 72 mg/kg/day for males and females).
3. A 3-month rat feeding study using doses of 0, 150,
and 600 ppm (equivalent to 0, 7.5, and 30 mg/kg bwt/day for
males and females) demonstrated a decrease in body weight,
decrease in hematocrit values, eosinophil count and medium
cell hemoglobin and increase in the high dose group and dose-
related increase in liver weight. The NOEL is 150 ppm and (
the LEL is 600 ppm.
°Non-Rodent Feeding Study
1. A 2-year male and female dog feeding study using doses
of 0, 150, 600 and 2400 ppm (equivalent to 0, 3.75, 15, and
60 mg/kg bwt/day for males and females). The NOEL is 150 ppm
based on changes in enzyme levels (equivalent to 3.75 mg/kg
bwt/day for males and females). The LEL is 600 ppm. Although
there were significant decreases in mean body weights in males
receiving 150 and 2400 ppm and in females receiving 600 and 2400
ppm, the biological significance of these changes could not be
assessed. There were noted increases in alkaline phosphatase
N-demethylase, and cytochrome P-450 in males receiving 2400 ppm
and significant increases in N-demethylase in females receiving
600 and 2400 ppm and in cytochrome P-450 in females receiving
2400 ppm when compared to controls.
2. A 6-month dog feeding study using doses of 0, 10, 30,
and 100 ppm (equivalent to 0, 0.25, 0.75, 2.5 mg/kg bwt/day
for males and females). The NOEL was demonstrated at doses
up to 100 ppm, the highest dose level tested.
3. A 3-month dog feeding study using doses of 0, 150, 600
and 2400 ppm (equivalent to 0, 3.75, 15, and 60 mg/kg bwt/day
for males and females). Weight gain in all male groups and
in the highest dose female group was significantly less than *
the control. Alkaline phosphatase in males and females showed f
a dose-related negative trend. There was no gross pathological
changes. Effects at 600 ppm included an increase in serum
cholesterol level in males. Although the NOEL appeared to be
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less than 150 ppm based on reduced body weight and decreased
alkaline phosphatase in males, the Agency has concluded that effects
below 600 ppm in the 2-year dog study were not biologically
significant and the longer-term study supercedes the 90-day dog
study. Therefore, the NOEL remains at 150 ppm.
°Teratology
1. A rabbit teratology study with a NOEL for maternal
toxicity of 8 mg/kg. The maternal LEL was 40 mg/kg based on
decreased body weight gains and food consumption. The develop-
mental NOEL and LEL were 40 mg/kg and 200 mg/kg respectively.
This study has to be resubmitted with all the findings
statistically analyzed on a per litter and per fetus basis in order
to be upgraded from its current classification as core supplementary.
2. A rat teratology study using dose levels 0, 30, 60,
and 120 mg/kg/day was determined to be core supplementary
because the NOEL for developmental toxicity (supernumerary ribs)
was not definitively established. The NOEL and LOEL for maternal
toxicity for this study are 30 and 60 mg/kg/day, respectively,
based on decreases in maternal body weight, body weight gain,
and food consumption at 60 and 120 mg/kg/day. Furthermore,
increased embryolethality (embryotoxicity) was only observed
at the highest dose level tested (120 mg/kg/day). This study
must be repeated to clearly define a NOEL for developmental
toxicity.
The above rat study indicated that triadimenol caused a
dose-dependent, statistically significant increase in the
incidence of rudimentary supernumerary ribs. Although the
effect at the low dose level was not statistically significant,
it was considered to be treatment related because of the dose-
related trend.
The biological significance of the manifestation of
supernumerary ribs is subject to scientific debate, especially
if the ribs are not fully developed (rudimentary). Nonetheless,
the margin of safety (MOS) for this effect must be taken into
consideration. The MOS is the ratio between the NOEL for the
effect and the acute exposure in mg/kg/day. A NOEL for
developmental toxicity could not be defined in the rat teratology
study but it is unlikely to be far below the threshold (LEL)
of 30 mg/kg/day observed in the current study.
Based on worker exposure information and an estimation of
the NOEL at about 15 mg/kg/day for developmental toxicity
(rudimentary supernumerary ribs in rats) and assuming a maximum
dermal penetration of about 10%, a margin of safety was calculated
to be >100 for factory workers involved in seed treatments using
a closed system. Because of possible developmental toxicity
and the lack of a will defined NOEL for this effect, the product
label must include a recommendation for the use of protective
clothing by factory workers involved in the treatment of seeds
and for farm workers handling the treated seed.
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production.
A rat multigeneration reproduction study using doses of
20, 100, and 500 ppm (equivalent to 0, 1, 5, and 25 mg/kg
/day for males and females) indicated that the NOEL and
L for both parental and pup toxicity are 100 and 500 ppm,
pectively, based on significant body weight and organ weight
nges. The NOEL for reproductive toxicity is 500 ppm, highest
e level tested.
tagenicity:
A reverse" mutation assay (AMES), a dominant lethal
t in mice, DNA damage/repair, unscheduled DNA synthesis,
yitro and in vivo (rat) cytogenic assays, and a forward
ation in mice, all of which were negative for mutagenic
acts.
ERONMENTAL FATE
Hydrolysis: STABLE. Triadimenol in sterile aqueous buffer
solutions showed no apparent degradation
at either temperature or pH tested.
Recovery was 97% greater after 32 days of
incubation.
Soil Surface Photolysis: STABLE. Triadimenol appears to
be stable to photolysis on the soil surface.
Studies indicate that triadimenol photodegrades
with a half-life of 36 hours in distilled
water and 17 hours in a photo-sensitized
(acetone) solution.
Aerobic Soil Metabolism: STABLE. Studies indicate that
triadimenol has an estimated aerobic half-life
of 8 to 9 months. Triadimenol reached a maximum
level of 68% of that applied at 14C in 71 days
and declined slightly to 45.2% by day 238.
Consequently, the anaerobic half-life is
considerably greater than 8-9 months.
Adsorption/Desorption: Because of its low adsorption
coefficients, triadimenol is shown to have a low
to moderate potential to bind to soil particles.
Studies indicate that the adsorption coefficient,
k, for triadimenol ranged from 2.37 to 5.26.
The k values for desorption ranged from 1.49
in a silty clay soil (0.49 ppm) to 9.12 in a
loam soil (9.57 ppm). Consequently, there
is no correlation between adsorption and
soil organic matter content. The highest
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degree of adsorption was observed with the
loam soil, intermediate in organic matter
content.
Environmental fate data requirements have been satisfied
with the exception of a field dissipation study. The company will
be required to submit results of this study by July 1990.
ECOLOGICAL CHARACTERISTICS
Studies submitted show that this chemical is practically
non-toxic to birds, slightly toxic to fish and moderately
toxic to1aquatic invertebrates. It is unlikely that the seed
treatment use of triadimenol will affect any terrestrial or
aquatic animals. Chronic effects are unlikely due to the low
use rates and because the seed treatment use requires incorporation
of seeds into the soil. For the above reasons it is also
unlikely that this use will affect any endangered species.
BENEFITS
This chemical has been shown to be environmentally safe,
is used at low rates and has a broad biological spectrum.
Triadimenol controls seed-, soil-, and wind-borne pathogens of
wheat, barley, oats, rye, corn and sorghum. Crops may be
grazed 40 days after seeding. The chemical improves winter
survival and drought tolerance of cereals, lowers the inoculum
levels for overwintering foliar diseases and may eliminate
the need for early season foliar sprays.
TOLERANCE ASSESSMENT;
Tolerances are established for the fungicide triadimenol
and its butanediol metabolite (calculated as triadimenol) in or
on the following commodities: 2.5 ppm for green forage of
barley, oats, rye and wheat; 0.1 ppm for straw of barley, oats,
rye and wheat; 0.05 ppm for grains of barley, oats, rye and wheat,
corn fodder, fresh corn (including sweet), corn forage, corn
grain, and green forage of sorghum; and 0.01 ppm for sorghum grain and
sorghum fodder. Tolerances are established for the fungicide
triadimenol and its metabolites containing the chlorophenoxy
moiety (calculated as triadimenol) in or on the following
commodities: 0.1 ppm for fat, meat and meat by-products of cattle,
goats, hogs, horses, and sheep; and 1.01 ppm for eggs, milk, and fat,
meat and meat by-products of poultry.
Where tolerances are established for residues of both l-(4-
chlorophenoxy)-3,3-dimethyl-l-(lH-l,2,4-triazol-l-yl)-2-butanone
(triadimefon) and triadimenol, including its butanediol metabolite,
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in or on the same raw agricultural commodity and its products
thereof, the total amount of such residues shall not yield more
residue than that permitted by the higher of the two tolerances.
The nature of the residue is adequately understood and the
Agency concluded that the pesticide is useful for the purposes
for which tolerances are sought and that the establishment of
the tolerances will protect the public health.
SUMMARY OF MAJOR DATA GAPS;
The Agency concurs with conditional registration of this
chemical for use as a seed treatment fungicide pending submission
of a field dissipation study by July 1990.
CONTACT PERSON AT EPA
Susan T. Lewis,
Acting Product Manager (PM) 21,
Registration Division (H-7505C),
Environmental Protection Agency,,
401 M St., SW.,
Washington, DC 20460
Office location and telephone number:
Rm. 227, CM#2,
1921 Jefferson Davis Highway,
Arlington, VA 22202
(703) 557-1900
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.
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United States
Environmental Protection Agency
Office of Pesticide Program (H7S04C)
PMSD, Information Services Branch
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