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Propiconazole

Publication Date: 10/97

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

  1. Worthing, C. R., ed. 1983. The pesticide manual: A world compendium. Croydon, England: The British Crop Protection Council.
  2. Technical Information Bulletin for Propiconazole Fungicide. Ciba-Geigy. Greensboro, NC. 15 pp.
  3. Technical Paper. Banner: A Turf Fungicide. Ciba-Geigy. Greensboro, NC. 21 pp.
  4. W. T. Thomson. 1997. Agricultural Chemicals. Book IV: Fungicides. 12th edition. Thomson Publications, Fresno, CA.
  5. Farm Chemicals Handbook. 1997. Meister Publishing Co. Willoughby, OH.
  6. U.S. Environmental Protection Agency. Propiconazole; Pesticide Tolerances for Emergency Exemptions. Federal Register Document 96-29020. November 12, 1996.
  7. 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.