Propiconazole (150 mg/kg, gavage, 14 days of medication) can induce specific hepatic P450 isoforms [1].

Animal/Disease Models: Adult male SD (SD (Sprague-Dawley)) rat [1]. Usage and
Doses: intragastric (po) (po)administration.
Route of Administration: 10, 75, 150 mg/kg, intragastrically (po) (po) for 14 days.
Experimental Results: In rat livers, propiconazole at a dose of 150 mg/kg body weight/day caused diffuse mild panlobular hepatocellular hypertrophy.

Absorption, Distribution and Excretion
After oral administration to rats, propiconazole is rapidly absorbed and also rapidly and almost completely eliminated with urine and feces. Residues in tissues were generally low and there was no evidence for accumulation or retention of propiconazole or its metabolites.
Male and female mice were fed a diet containing 5, 100 and 2500 ppm propiconazole for 21 days, followed by a single oral dose of (14C)-phenyl propiconazole at a mean corresponding dose level (0.8/1.0, 16.8/21.5 and 434/475 mg/kg bw for males/females). Urinary excretion accounted for 45-81% of the administered dose after 96 hours and tended to be higher by males than by females. In the feces 22-43% was excreted. At the lowest dose level (5 ppm propiconazole) the residual radioactivity in blood, liver, kidneys, lungs and in the remaining carcass was below 0.02 mg/kg propiconazole equivalents and accordingly higher at the 100 and 2500 ppm dose level. Residues in female mice were higher than in male mice, except in the kidneys where the males showed higher or equal values. Independent of the dose level and sex of the animals, the highest residues were found in the liver, up to 2.3 and 3.0 mg/kg in males and females of the highest dose level, respectively.
Orally administered single doses (0.5 and 25 mg/kg bw) of triazole labelled (3,5-14C)-propiconazole to rats were rapidly excreted within 24 hours (74-84%). After 6 days, 0.04-0.15%, 28-46% and 53-67% had been recovered from expired air, feces and urine respectively. Only about 0.4% of the administered dose remained in the tissues. Highest tissue residues were found in liver, blood and kidneys. No unchanged propiconazole was excreted in the urine. Within 3 days after treatment of male rats with a single oral dose of about 32 mg/kg bw of triazole labelled (3,5-14C)-propiconazole or a phenyl-(U-14C) labelled propiconazole, more than 95% of the dose was excreted. Of this, 52% was found in the urine and 43-48% in the feces. The excretion pattern for both compounds was identical with no administered compound being found in the urine.
Single doses of triazole-14C-propiconazole (1.0 and 10.0 mg/kg bw) applied dermally to rats were absorbed through the skin following first order kinetics with half-lives averaging 24-31 hours for low and high dosed rats, respectively. Equal amounts of the dose were excreted within 72 hours in urine and feces. The amount of residual radioactivity on the skin averaged 20% of the applied dose.
Feed consumption, milk production or the general health of a lactating goat were not affected after the daily oral administration of 5 mg triazole-14C-propiconazole for 10 consecutive days (which would correspond to 4.5 ppm in the feed). Of the total dose, 89% was excreted within 24 hours after the last administration (68% and 21% in urine and feces, respectively). All tissues contained less than 0.02 mg/kg propiconazole equivalents, except liver (0.096 mg/kg) and kidney (0.029 mg/kg). The total radioactivity secreted with the milk reached a plateau at day three of 0.013-0.016 mg/kg, representing 0.18% of the total dose.

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Metabolism / Metabolites
The metabolism of orally administered (14C)-phenyl propiconazole was studied in mice pretreated with unlabeled propiconazole followed by a single oral dose of (14C)-phenyl propiconazole at a corresponding dose level. The urinary metabolite pattern of propiconazole demonstrated a marked sex dependency. In male mice, 60% of the radioactivity in 0-24 hour urine was represented by one metabolite, this metabolite accounted for 30% in the 0-24 hour urine in female mice. This metabolite was identified by spectroscopy as the glucuronic acid conjugate of 1-(2,4-dichlorophenyl)-2-(1 H-1,2,4-triazol-1-yl) ethanol. This demonstrates that the major metabolic pathway in mice involves dioxolane ring cleavage.
The metabolism of propiconazole was investigated in male rats administered a single oral dose of 31.4 mg/kg triazole-(3,5-14C-propiconazole). Metabolites were isolated from first day urine and feces excretion representing 44.5% and 36.2% of the applied dose, respectively. A wide array of biotransformations occurred leading to numerous metabolites. The major site of enzymatic attack oxidation of the propyl side chain leading via alcohols and diols to carboxy acids and alpha-hydroxy carboxy acid or cleavage of the dioxolane ring. The majority of the alcoholic and phenolic metabolites are renally excreted as sulfuric acid and glucuronic acid conjugates. In the rat the main metabolite is the alpha hydroxyl carboxylic acid of propiconazole.
/In rats/...the major sites of enzymic attack are the propyl side-chain and the cleavage of the dioxolane ring, together with some attack at the 2,4-dichlorophenyl and 1,2,4-triazole rings. In mice, the major metabolic pathway is via cleavage of the dioxolane ring.

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Biological Half-Life
Half-live averages 24-31 hours /in rats/.

Toxicity Summary
Propiconazole can decrease cholesterol levels that may cause polyploidy and disruption of mitotic cell cycling. It down-regulates the PTEN pathway and up-regulates the WNT-beta-catenin signaling pathway, that would stimulate cell proliferation and may lead to the tumorigenic outcome. (A15329)

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Toxicity Data
LC50 (rat) =1,264 mg/m3/4h

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Non-Human Toxicity Values
LD50 Rat oral 1,517 mg/kg
LD50 Rat percutaneous >4,000 mg/kg
LD50 Rabbit percutaneous >6,000 mg/kg
LC50 Rat inhalation >5,800 mg/cu m/4 hr
LD50 Mouse oral 1490 mg/kg

[1]. Propiconazole-induced cytochrome P450 gene expression and enzymatic activities in rat and mouse liver. Toxicol Lett. 2005 Feb 15;155(2):277-87.

[2]. Single and Combined Cytotoxicity Research of Propiconazole and Nano-zinc Oxide on the NIH/3T3 Cell. Procedia Environmental Sciences Volume 18, 2013, Pages 100-105.

Yellowish odorless liquid. Non corrosive. Used as a fungicide.
Propiconazole is the cyclic ketal obtained by formal condensation of 1-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethanone with pentane-1,2-diol. A triazole fungicide, it is used commercially as a diastereoisomeric mixture on soft fruit (including apricots, peaches, nectarines, plums and prunes), nuts (including peanuts, pecans and almonds), mushrooms, and grasses grown for seeds. It has a role as a xenobiotic, an environmental contaminant, an EC 1.14.13.70 (sterol 14alpha-demethylase) inhibitor and an antifungal agrochemical. It is a member of triazoles, a cyclic ketal, a dichlorobenzene, a conazole fungicide and a triazole fungicide.
Propiconazole is a triazole fungicide, also known as a DMI, or demethylation inhibiting fungicide due to its binding with and inhibiting the 14-alpha demethylase enzyme from demethylating a precursor to ergosterol. Without this demethylation step, the ergosterols are not incorporated into the growing fungal cell membranes, and cellular growth is stopped. Propiconazole is used agriculturally on turfgrasses grown for seed and aesthetic or athletic value, mushrooms, corn, wild rice, peanuts, almonds, sorghum, oats, pecans, apricots, peaches, nectarines, plums and prunes. It is also used in combination with permethrin in formulations of wood preserver. Propiconazole is a mixture of four stereoisomers and was first developed in 1979 by Janssen Pharmaceutica.

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Mechanism of Action
A first version cDNA microarray of the cladoceran Daphnia magna /was developed/. Through Suppression Subtractive Hybridization PCR (SSH-PCR) 855 life stage-specific cDNAs were collected and used to document the toxicological mode of action of the pesticide propiconazole. DNA sequencing analysis revealed gene fragments related to important functional classes such as embryo development, energy metabolism, molting and cell cycle. Major changes in transcription were observed in organisms exposed for 4 and 8 days to 1 microg/mL. After 4 days a 3-fold down-regulation of the gene encoding the yolk protein, vitellogenin, was observed indicating impaired oocyte maturation. Moreover, genes such as a larval-specific gene and chaperonin were repressed, whereas the heat shock 90 protein and ATP synthase were induced. Organismal effects clearly confirmed the major molecular findings: at the highest concentration (1 ug/mL) adult growth was significantly (p < 0.05) impaired and increased developmental effects in the offspring could be noted. We have demonstrated the potential of microarray analysis in toxicity screening with D. magna. The use of vitellogenin mRNA as a rapid biomarker of reproductive effects in chronic toxicity studies with cladocerans is suggested.

C15H17CL2N3O2

342.22

341.069

60207-90-1

Propiconazole-d7;1246818-14-3;Propiconazole-d3 nitrate;2699607-26-4

43234

Yellowish, viscous liquid
White crystalline powder
Colorless solid

1.4±0.1 g/cm3

480.0±55.0 °C at 760 mmHg

244.1±31.5 °C

0.0±1.2 mmHg at 25°C

1.624

3.88

0

4

5

22

377

0

CCCC1OC(CN2N=CN=C2)(C3=CC=C(Cl)C=C3Cl)OC1

STJLVHWMYQXCPB-UHFFFAOYSA-N

InChI=1S/C15H17Cl2N3O2/c1-2-3-12-7-21-15(22-12,8-20-10-18-9-19-20)13-5-4-11(16)6-14(13)17/h4-6,9-10,12H,2-3,7-8H2,1H3

1-[[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]-1,2,4-triazole

CGA-64250; Desmel; Propiconazole

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~292.21 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.31 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (7.31 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (7.31 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)