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
Following oral administration of propiconazole to rats, it is rapidly absorbed and almost completely excreted in urine and feces. Tissue residues are typically low, and there is no evidence of accumulation or retention of propiconazole or its metabolites. Male and female mice were fed diets containing 5, 100, and 2500 ppm propiconazole, respectively, for 21 days, followed by a single oral dose of (14C)-phenylpropiconazole. The mean dose levels were: males 0.8/1.0 mg/kg body weight, females 16.8/21.5 mg/kg body weight, and males 434/475 mg/kg body weight. Ninety-six hours later, urinary excretion accounted for 45-81% of the administered dose, with males generally excreting more than females. Fecal excretion accounted for 22-43% of the administered dose. At the lowest dose level (5 ppm propiconazole), residual radioactivity in blood, liver, kidney, lung, and remaining carcass was below 0.02 mg/kg propiconazole equivalent; therefore, residual radioactivity was higher at dose levels of 100 ppm and 2500 ppm. Except for the kidney, residual levels were higher in female mice than in male mice, while residual levels in the kidneys of male mice were higher or comparable to those in female mice. Regardless of dose level or sex, the highest residual levels were found in the liver, reaching as high as 2.3 mg/kg in male mice and 3.0 mg/kg in female mice at the highest dose levels. Following oral administration of a single dose (0.5 and 25 mg/kg body weight) of triazole-labeled (3,5-14C)-propiconazole to rats, 74-84% was rapidly eliminated from the body within 24 hours. Six days later, 0.04–0.15%, 28–46%, and 53–67% of the drug were recovered from exhaled breath, feces, and urine, respectively. Only about 0.4% of the administered dose remained in tissues. The highest drug residues were found in the liver, blood, and kidneys. Unmetabolized propiconazole was not detected in urine. In male rats, more than 95% of the dose was excreted within 3 days following a single oral administration of approximately 32 mg/kg body weight of triazole-labeled (3,5-14C)-propiconazole or phenyl-(U-14C)-labeled propiconazole. Of this, 52% was excreted in urine and 43–48% in feces. Both compounds were excreted using the same pattern, and the administered compounds were not detected in urine.
Following a single transdermal administration of triazole-14C-propiconazole (1.0 and 10.0 mg/kg body weight) to rats, the drug was absorbed kinetically according to first-order kinetics, with half-lives of 24–31 hours in the low- and high-dose groups, respectively. Within 72 hours, the dose excreted in urine and feces was equal. The average residual radioactivity on the skin was 20% of the administered dose.
After 10 consecutive days of oral administration of 5 mg triazole-14C-propiconazole (equivalent to a feed concentration of 4.5 ppm), feed intake, milk production, and overall health of lactating goats were not affected. Within 24 hours of the last administration, 89% of the total dose was excreted (68% in urine and 21% in feces). Except for the liver (0.096 mg/kg) and kidneys (0.029 mg/kg), the propiconazole equivalent in all tissues was less than 0.02 mg/kg. Total radioactivity secreted in breast milk plateaued on day 3, ranging from 0.013 to 0.016 mg/kg, representing 0.18% of the total dose. Metabolism/Metabolites: This study investigated the metabolism of orally administered (14C)-phenylpropiconazole in mice pretreated with unlabeled propiconazole, followed by a single oral dose of the appropriate amount. The urinary metabolite pattern of propiconazole exhibited a clear sex-dependent characteristic. In male mice, 60% of the radioactivity in 0–24 hour urinary urine was attributed to a single metabolite; while in female mice, this metabolite accounted for 30% of the 0–24 hour urinary radioactivity. Spectroscopic analysis identified this metabolite as a glucuronic acid conjugate of 1-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethanol. This indicates that the major metabolic pathway in mice involves the cleavage of dioxolane. This study investigated the metabolism of propiconazole in male rats after a single oral dose of 31.4 mg/kg triazole-(3,5-14C-propiconazole). Metabolites were isolated from urine and feces on day 1, representing 44.5% and 36.2% of the administered dose, respectively. Multiple biotransformations occurred, generating various metabolites. The main enzymatic reaction sites were the oxidation of the propyl side chain, via alcohols and diols to carboxylic acids and α-hydroxycarboxylic acids, or the cleavage of the dioxolar ring. Most alcohol and phenolic metabolites were excreted by the kidneys as sulfate and glucuronic acid conjugates. In rats, the main metabolite was the α-hydroxycarboxylic acid of propiconazole. In rats, the main enzymatic reaction sites were the cleavage of the propyl side chain and the dioxolar ring, and the partial cleavage of the 2,4-dichlorophenyl and 1,2,4-triazole rings. In mice, the main metabolic pathway was via the cleavage of the dioxolar ring.

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Biological half-life
In rats, the average half-life is 24–31 hours.

Toxicity Summary
Propiconazole lowers cholesterol levels, which may lead to polyploid and mitotic cell cycle disorders. It downregulates the PTEN pathway and upregulates the WNT-β-catenin signaling pathway, thereby stimulating cell proliferation and potentially leading to tumorigenesis. (A15329) Toxicity Data
LC50 (Rat) = 1,264 mg/m³/4h Non-Human Toxicity Values LD50 (Rat, Oral) 1,517 mg/kg LD50 (Rat, Dermal) >4,000 mg/kg LD50 (Rabbit, Dermal) >6,000 mg/kg LC50 (Rat, Inhalation) >5,800 mg/m³/4hr 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.

Pale yellow, odorless liquid. Non-corrosive. Used as a fungicide. Propiconazole is a cyclic ketal formed by the condensation of 1-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethyl ketone with pentane-1,2-diol. It is a triazole fungicide, commercially available in diastereomer mixtures for soft fruits (including apricots, peaches, nectarines, plums, and prunes), nuts (including peanuts, pecans, and almonds), mushrooms, and seed grasses. It is an exogenous substance, environmental pollutant, EC 1.14.13.70 (sterol 14α-demethylase) inhibitor, and antifungal pesticide. Propiconazole belongs to the triazole fungicide class, cyclic ketal class, dichlorobenzene fungicide, azole fungicide, and triazole fungicide class. Propiconazole is a triazole fungicide, also known as a DMI (demethylation inhibitor) fungicide, because it binds to 14α-demethylase and inhibits its demethylation of ergosterol precursors. Without this demethylation step, ergosterol cannot integrate into the cell membrane of growing fungi, leading to cell growth arrest. Propiconazole is used in agriculture for lawns (for seed production, ornamental, or sports purposes), mushrooms, corn, wild rice, peanuts, almonds, sorghum, oats, pecans, apricots, peaches, nectarines, plums, and prunes, among other crops. It is also used in combination with permethrin in wood preservative formulations. Propiconazole is a mixture of four stereoisomers and was first developed by Janssen Pharmaceuticals in 1979.

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Mechanism of Action
We constructed the first cDNA microarray of the cladoceran Daphnia magna.
We collected 855 life-stage-specific cDNAs using suppression subtractive hybridization PCR (SSH-PCR) to elucidate the toxicological mechanism of action of the insecticide propiconazole. DNA sequencing analysis revealed gene fragments associated with important functional categories such as embryonic development, energy metabolism, molting, and cell cycle. Significant changes in transcription were observed in organisms exposed to 1 μg/mL propiconazole for 4 and 8 days. After 4 days, the expression of the gene encoding vitellogenin was downregulated 3-fold, indicating impaired oocyte maturation. Furthermore, the expression of larva-specific genes and molecular chaperones was suppressed, while the expression of heat shock protein 90 and ATP synthase was induced. The organismal effects also clearly confirmed the key molecular findings: at the highest concentration (1 μg/mL), adult growth was significantly impaired (p < 0.05), and progeny development was inhibited. We have demonstrated the potential of microarray analysis in toxicity screening of the large flea (D. magna). It is recommended that vitellogenin mRNA be used as a rapid biomarker for reproductive effects in chronic toxicity studies of cladocerans.

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.)