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Pesticide
Information
Profile
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Propiconazole
Publication Date: 10/97
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TRADE OR OTHER NAMES
The active ingredient propiconazole is a triazole fungicide that has
protective, curative, and systemic activity. Some trade names for products
containing propiconazole include Banner, Benit, Desmel, Orbit, Radar, Tilt,
Fidis, Alamo, Spire, Practis, Bumper, Mantis, Restore, Banner Maxx, Taspa,
Juno, Novel and Break. Formulations come as a emulsifiable concentrates and
wettable powders. It is also formulated with other pesticides (4, 5).
REGULATORY STATUS
Propiconazole was first developed in 1979 by Janssen Pharmaceuticals of
Belgium. It is now being marketed by Ciba (4, 5).
INTRODUCTION
Propiconazole is a systemic foliar fungicide with a broad range of
activity. It is used on grasses grown for seed, mushrooms, corn, wild rice,
peanuts, almonds, sorghum, oats, pecans, apricots, peaches, nectarines, plums
and prunes. On cereals it controls diseases caused by Erysiphe graminis,
Leptosphaeria nodorum, Pseudocerosporella herpotrichoides, Puccinia spp.,
Pyrenophora teres, Rhynchosporium secalis, and Septoria spp. (1, 2, 4).
Propiconazole's mode of action is demethylation of C-14 during ergosterol
biosynthesis, and leading to accumulation of C-14 methyl sterols. The
biosynthesis of these ergosterols is critical to the formation of cell walls
of fungi. This lack of normal sterol production slows or stops the growth of
the fungus, effectively preventing further infection and/or invasion of host
tissues. Therefore, propiconazole is considered to be fungistatic or growth
inhibiting rather than fungicidal or killing (2).
TOXICOLOGICAL EFFECTS
ACUTE TOXICITY
The acute toxicity to mammals for propiconazole technical are an acute
oral LD50 for rats of 1,517 mg/kg and 1,344 mg/kg for rabbits. The acute
dermal LD50 for rabbit was reported to be >4,000 mg/kg. Propiconazole was
considered a slight irritant in rabbit skin and eye irritation studies. A skin
sensitization study in guinea pigs demonstrated no allergic effect (2).
The acute toxicity to mammals for the formulated products Orbit 3.6E,
Tilt 3.6E and Banner 1.1E was as follows: acute oral LD50 for rats of 1,310
mg/kg. The acute dermal LD50 for rabbit was reported to be >5,010 mg/kg. The
formulated products were considered a moderate irritant in rabbit skin and eye
irritation studies. A skin sensitization study in guinea pigs resulted in the
formulated product being considered a sensitizer (2, 3).
EPA toxicologists have recommended that the developmental No-Observed-
Effect-Level (NOEL) of 30 mg/kg/day from the rat developmental toxicity study
be used for acute dietary risk calculations. The lowest-effect-level (LEL) of
90 mg/kg/day is based on the increased incidence of unossified sternebrae,
rudimentary ribs, and shortened or absent renal papillae.
CHRONIC TOXICITY
In two-year feeding studies in mice, the NOEL was established at 100 ppm.
Significant increases were noted in the incidence of spontaneous liver tumors
(benign) observed in male mice at the highest feeding level only. In two-year
rat feeding studies, the no-effect-level was established at 100 ppm. There
were no tumors in the rat at any feeding level. In one-year feeding studies in
dogs, the NOEL was established at 250 ppm, the highest level tested (2).
Based on the available chronic toxicity data, EPA has established the RfD
for propiconazole at 0.013 mg/kg/day. This RfD is based on a 1 year dog
feeding study with a NOEL of 1.25 mg/kg/day and an uncertainty factor of 100.
The uncertainty factor of 100 was applied to account for inter-species
extrapolation and intra-species variability. Mild irritation of the gastric
mucosa was the effect observed at the LEL of 6.2 mg/kg/day (6).
A 21-day subchronic dermal toxicity test in rabbits found after 3 weeks
(15 applications) moderate skin irritation to be the only effect following
applications of propiconazole at 1000 mg/kg/day (2).
Reproductive Effects
Over a two-year period, rats and their offspring were fed a diet
containing propiconazole at concentrations up to 2,500 ppm. Although the high
dose resulted in diminished body weight, and increases in relative liver
weight of adults and pups, no reproductive, foetal, or embryonic parameters
were affected (2).
EPA notes developmental toxicity NOELs of 30 mg/kg/day in rats and 400
mg/kg/day, the Highest Dose Tested (HDT) in rabbits. Developmental toxicity
was observed in rats at 90 mg/kg/day; these effects occurred in the presence
of maternal toxicity. In rabbits, no developmental delays or alterations were
noted; increased abortions were observed at the maternally toxic dose of 400
mg/kg/day. The developmental NOELs are more than 24- and 320-fold higher in
rats and rabbits, respectively, than the NOEL of 1.25 mg/kg/day from the 1-
year feeding study in dogs, which is the basis of the RfD (6).
In the two-generation reproductive toxicity study in the rat, the
reproductive/developmental toxicity NOEL of 25 mg/kg/day was greater than the
parental (systemic) toxicity NOEL (<5 mg/kg/day; Lowest Dose Tested (LDT)).
EPA notes that the NOEL of 25 mg/kg/day, for reproductive (pup) toxicity, was
20-fold higher than the NOEL of 1.25 mg/kg/day from the 1-year feeding study
in dogs, which is the basis of the RfD. The reproductive (pup) LEL of 125
mg/kg/day was based on decreased offspring survival of second generation (F2)
pups, and on decreased body weight throughout lactation, and an increase in
the incidence of hepatic cellular swelling for both generations of offspring
(F1 and F2 pups). Because these reproductive effects occurred in the presence
of parental (systemic) toxicity, these data do not suggest an increased post-
natal sensitivity to children and infants (that infants and children might be
more sensitive than adults) to propiconazole exposure (6).
Teratogenic Effects
Propiconazole was administered orally in doses up to 300 mg/kg/day during
days 6-15 post-conception in rats, and up to 180 mg/kg/day on days 6-18 of
gestation to Chinchilla rabbits. No teratogenic or foetotoxic effects were
observed from either group, at any dose (2).
Mutagenic Effects
No evidence of mutagenic potential were seen in the following studies:
Gene Mutation - Ames test, mouse lymphoma test in-vitro, in-vitro test with
saccharomyces cerevisiae and mouse lymphoma test, host mediated assay (2).
Chromosomal Aberration - Dominant lethal test, cytogenetic study in
spermatogonia, cytogenetic study in spermatocytes, and a nucleus anomaly test
(2).
Primary DNA damage - Unscheduled DNA synthesis test (human fibroblasts),
unscheduled DNA synthesis test (rat hepatocyte) and sister chromatin exchange
test (2).
Carcinogenic Effects
In 2-year feeding studies, the no-effect-level was established at 100
ppm. There were no tumors in the rat at any feeding level (2).
Using its Guidelines for Carcinogen Risk Assessment published September
24, 1986 (51 FR 33992), EPA has classified propiconazole as Group "C" for
carcinogenicity (possible human carcinogen). The Cancer Peer Review Committee
recommended the RfD approach for quantitation of human risk. Therefore, the
RfD is deemed protective of all chronic human health effects, including cancer
(6).
Organ Toxicity
No information was found.
Fate in Animals and Humans
Animals rapidly metabolize propiconazole to a wide variety of compounds.
The n-propyl side chain of the dioxolane ring can be oxidized to give a series
of metabolites consisting of formic, acetic, and propionic acids. The
propionic acid group can be further oxidized to an alpha-hydroxy acid.
Cleavage of the dioxolane ring and deketalization yields the alkanol
metabolite. Alterations of the phenyl ring of the alkanol yield dechlorinated
and hydroxylated ring metabolites that rapidly form glucuronic acid and
sulfuric acid conjugates (2).
ECOLOGICAL EFFECTS
Effects on Birds
Propiconazole had the following LD50s for avian species: mallard duck
>2,510 mg/kg, Peking duck >3,000 mg/kg, Japanese quail 2,223 mg/kg, and
bobwhite quail 2,825 mg/kg (2).
Effects on Aquatic Organisms
Propiconazole had the following EC50/LC50 values in ppm for freshwater
fish species: bluegill 1.3-10.2, brown trout 3.3, rainbow trout 0.9-13.2, carp
6.8-21.0, catfish 2.0-5.1, and fathead minnow 7.6 (2). Another laboratory
trial found LC50 (96-hour) values to be 20 mg/l water for brown trout and >100
mg/l for carp (1).
Propiconazole had the following EC50/LC50 values in ppm for freshwater
invertebrate species: crayfish 42.0, water flea 3.2-11.5. The marine species
oyster and Mysid shrimp had EC50/LC50 values of 0.3 and 0.5-1.4, respectively
(2).
Effects on Other Animals (Nontarget species)
Propiconazole does not appear to have any adverse effects on soil
microbes as evidenced by soil biochemical analyses. Evaluations were made at
concentrations up to and including 100 ppm. At this highest level, no changes
were observed in cellulose, starch, or protein decomposition, nitrification,
nitrogen fixation, or respiration.
Propiconazole displayed no toxic effects to earthworms (2).
ENVIRONMENTAL FATE
Breakdown of Chemical in Soil and Groundwater
The soil movement and leaching potential of propiconazole is limited.
Mobility is restricted in soils high in montmorillonite clay and/or organic
matter. Also, soil movement is less in acidic soils. Leaching in soils that
are acidic, and high in clay and organic matter will be restricted to the top
2-3 inches. In alkaline, low organic matter soils (typical of the Southwestern
U.S.), propiconazole may leach to a maximum depth of 8-10 inches. Therefore,
leaching into underground water supplies is unlikely (2).
Propiconazole displays moderate soil longevity. In an aerobic soil under
controlled conditions, the soil half-life of C14-labeled propiconazole ranged
from 30 to 112 days, depending on where the C14 label was placed on the
molecule. Under field conditions, the longevity is somewhat higher. The half-
life under these conditions ranged from a low of 96 days in a sandy loam to
575 days in a silt loam in Texas. In North Carolina, the half-life in soil
dropped to 229 days (2).
Breakdown of Chemical in Surface Water
Propiconazole was evaluated at three pH concentrations (5, 7, 9), and a
standard temperature of 20 degrees C; no significant hydrolysis was observed.
Propiconazole is subject to photolysis, but after 12 days of exposure to
natural light, only 20% photolysis was recorded. However, using 1% acetone as
a photosensitizer, the half-life was reduced to <1 day. Therefore, should
propiconazole enter a natural pond situation (which contains several natural
photosensitizers), propiconazole should undergo rapid photodegradation (2).
Breakdown of Chemical in Vegetation
Propiconazole is readily absorbed by plant tissues, and is transported
systemically within the plant. Thus, leaves that emerge following the
application will also be protected from fungal infection. Systemic movement is
predominately upward (from roots to foliage, or lower leaves to upper leaves),
but limited downward translocation also occurs (2).
Plants metabolize propiconazole by hydroxylation of the n-propyl group on
the dioxolane ring to yield four beta-hydroxy isomers which form sugar
conjugates. Further metabolism involves cleavage of the dioxolane ring and
deketalization to form the alkanol metabolite. Hydroxylation and
dechlorination of the phenyl ring occur to some degree. Cleavage of the alkyl
bridge between the phenyl and triazole rings results in formation of a
triazole alanine conjugate which can undergo some oxidation (2).
PHYSICAL PROPERTIES AND GUIDELINES
Technical propiconazole is an odorless, yellowish, clear viscous liquid
(2).
Exposure Guidelines:
| NOEL: | 1.25 mg/kg/day (6) |
| RfD: | 0.013 mg/kg/day (6, 7) |
Physical Properties:
| CAS #: | 60207-90-1 |
| Chemical name: | 1-[[2(2,4-Dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]1-H-1,2,4-triazole (2) |
| Chemical Class/Use: | triazole fungicide that has protective, curative and systemic activity (4) |
| Solubility in water: | 100 ppm at 20 degrees C |
| Solubility in other solvents: | 100 % Soluble at 20 degrees C in methanol, acetone, Ether, chloroform and benzene; 6% in hexane (2) |
| Boiling point: | 180 degrees C at 0.1 mmHg (2) |
| Vapor pressure: | 1.3 x 10 to the minus 6 Torr @ 20 degrees C (2); 1.5 x 10 to the minus 5 Torr @ 40 degrees C |
BASIC MANUFACTURER
Ciba-Geigy Corporation
P.O. Box 18300
Greensboro, NC 27419-8300
Telephone: 800-334-9481
Emergency Telephone: 800-888-8372
Fax: 910-632-2861
Review by Basic Manufacturer:
Comments solicited: June, 1997
Comments received: None received
REFERENCES
Worthing, C. R., ed. 1983. The pesticide manual: A world compendium.
Croydon, England: The British Crop Protection Council.
Technical Information Bulletin for Propiconazole Fungicide. Ciba-Geigy.
Greensboro, NC. 15 pp.
Technical Paper. Banner: A Turf Fungicide. Ciba-Geigy. Greensboro, NC.
21 pp.
W. T. Thomson. 1997. Agricultural Chemicals. Book IV: Fungicides. 12th
edition. Thomson Publications, Fresno, CA.
Farm Chemicals Handbook. 1997. Meister Publishing Co. Willoughby, OH.
U.S. Environmental Protection Agency. Propiconazole; Pesticide
Tolerances for Emergency Exemptions. Federal Register Document 96-29020.
November 12, 1996.
U.S. Environmental Protection Agency. Pesticide Tolerances for 1-[[2-
(2,4-Dichlorophenyl)-4-Propyl-1,3-Dioxolan-2-yl]Methyl]-1H-1,2,4-Triazole and
its Metabolites Determined as 2,4-Dichlorobenzoic Acid and Expressed as Parent
Compound. Federal Register Document 93-12130. May 21, 1993.
Disclaimer: Please read
the pesticide label prior to use. The information contained at this web
site is not a substitute for a pesticide label. Trade names used herein
are for convenience only; no endorsement of products is intended, nor is
criticism of unnamed products implied. Most of this information is historical
in nature and may no longer be applicable.
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