The treatment Tebuconazole (TEB) (20–80 μM, 24 hours) leads HepG2 cells to accumulate nutrients [2]. In HepG2 cells, tebuconazole (20–80 μM, 12 hours) promotes peroxisome proliferation. Tebuconazole (20–80 μM, 24 hours) raises the HepG2 cells' mitochondrial membrane oxidation level. Protein is increased when bodily triglycerides are lost and oxidized. nutrients and oxidation-related markers' translocation and expression [2]. By activating the middle region of the ER, tebuconazole (0-750 μM, 24 levels) can impair MAC-T cell survival and proliferation and promote MAC-T cell inflammation [3]. Within H9c2 cells, tebuconazole (0 Tebuconazole (30–60 μM, 24 hours) can cause DNA damage and activity.

Tebuconazole (TEB) (10-50 mg/kg once daily for 28 days) induces multiple CYPs and EGFR, inhibits testicular P450 and glutathione S-transferase activity, reports Tebuconazole (25-100 mg/kg per day, continued for 10 days) causes fetal testicular Leydig cell proliferation during pregnancy and increases fetal testosterone and progesterone levels [6]. .Amoscanate (500 mg/kg; oral; 10 days) affects the ependyma and periventricular brain [1]. Amoscarate (250 and 500 mg/kg; oral; 28 days) induces medial striatal ependymal/subependymal localized necrosis, Ca++-positive microparticles, pyknosis, and edema [1]. Amoscarate (25 to 500 mg/kg; oral; 20 days) produces progressive ependymal necrosis [1]. Amoscanate induces severe ultrastructural damage to ependymal cells [1].

Western Blot analysis [2]
Cell Types: HepG2 cells
Tested Concentrations: 20, 40, 80 μM
Incubation Duration: 1– 12 hour
Experimental Results: Increased nuclear translocation of peroxisome proliferator-activated receptor. As well as expression of cluster of differentiation 36, fatty acid transport protein (FATP) 2, FATP5 and carnitine palmitoyltransferase 1.

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Apoptosis analysis [3 ]
Cell Types: Bovine Mammary Epithelial Cells (MAC-T cells)
Tested Concentrations: 100,150,200,250,500,750 μM
Incubation Duration: 24 hrs (hours)
Experimental Results: Cell viability and proliferation are diminished and induced by pro-apoptotic proteins such as cleaved caspases 3 and 8 and Upregulation of BAX) activates apoptotic cell death. Induces loss of mitochondrial membrane potential in MAC-T cells. Induces mitochondria-mediated apoptosis of MAC-T cells by activating ER stress. Induces endoplasmic reticulum (ER) stress by upregulating Bip/GRP78 stim; PDI; ATF4; cleavage; and ERO1-Lα.

Animal/Disease Models: Male Wistar rat [5]
Doses: 10, 25 and 50 mg/kg
Route of Administration: Orally, one time/day for 28 days
Experimental Results: Induction of CYP1A1/2, CYP2B1/2, CYP2E1 and CYP3A proteins in the liver . The glutathione content in the liver is diminished, and the activities of glutathione S-transferase, superoxide dismutase, catalase and glutathione peroxidase are increased. Superoxide dismutase activity is increased in the kidneys and testicles. Glutathione S-transferase activity is diminished in the testicles. Serum testosterone concentration and cauda epididymal sperm count diminished.

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Animal/Disease Models: Male and female SD (SD (Sprague-Dawley)) rats [6]
Doses: 25, 50 and 100 mg/kg
Route of Administration: po (oral gavage) for 10 days
Experimental Results: Increased fetal serum testosterone and progesterone levels. Increases the number of fetal Leydig cells per testis without inducing cell aggregation. Upregulates the expression levels of Star, Cyp11a1, Hsd17b3 and Fshr. AKT1, ERK1/2, and mTOR phosphorylation were increased, BCL2 levels

Absorption, Distribution and Excretion
/In animals/ after three days, elimination was almost complete (>99%). Tebuconazole was excreted with the urine and the feces.
(Phenyl-U-14C)-/tebuconazole/ (specific activity: 84.4 mCi/mg; radiochemical purity:> 99%) was administered to 5 rats/sex/group at single doses of 2 or 20 mg/kg or after repeated dosing of 2 mg/kg with non-radiolabeled test material for 14 days, a single dose of labeled material at 2 mg/kg. Radiolabeled material was assayed in the plasma, urine, and feces of all groups and in the bile and expired CO2 of one group each. Maximum relative plasma concentrations ranged from 0.11 to 0.20 and were achieved 0.33 to 1.7 hours after administration of the test material. After 72 hours, % excreted ranged from 91 to 98%. A difference in sex-related excretion of the test material was noted with males having a urine/feces ratio of 16/78 in contrast to the females which excreted at a ratio of 30/62. Biliary excretion was only measured in males. Ninety percent of the radiolabel was recovered in the bile after a single pass through the liver. Only 0.03% of the radiolabel was recovered in the expired air. Residual label in the tissues (excluding the gastrointestinal tract) ranged from 0.21 to 0.67% of the administered dose after 72 hours.
(Phenyl-U-14C)-/tebuconazole/ (specific activity: 84.4 mCi/mg; radiochemical purity: > 99%) was administered to 5 rats/sex/group at single doses of 2 or 20 mg/kg or after repeated dosing of 2 mg/kg with non-radiolabeled test material for 14 days, a single dose of labelled material at 2 mg/kg. (Triazole-3,5-14C)-/tebuconazole/ (specific activity: 56.5 mCi/mg; radiochemical purity-98.4%) was administered to 5 rats/sex at a single dose of 20 mg/kg. Radiolabeled material was assayed in the urine, and feces of all groups for up to 72 hours. The chemical structures of specific radiolabeled metabolites were identified. Females showed a higher renal elimination rate than males (26 to 35% vs. 15 to 18%, respectively). Conversely, males exhibited a higher portion of excreted radioactivity in the feces (77 to 80% vs. 60 to 67%, respectively).
After oral administration of tebuconazole to rats, 65-80% of the dose was eliminated by the biliary and fecal route, whereas elimination in urine amounted to about 16-35%. Males had a greater biliary and fecal elimination than females. Biotransformation proceeded by oxidation reactions, resulting in hydroxy, carboxy, triol and ketoacid metabolites and conjugates as well as triazole.
For more Absorption, Distribution and Excretion (Complete) data for TEBUCONAZOLE (6 total), please visit the HSDB record page.

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Metabolism / Metabolites
Biotransformation proceeded by oxidation reactions, resulting in hydroxy, carboxy, triol and ketoacid metabolites and conjugates as well as triazole.
Among the metabolites identified, oxidation of the #5 carbon of the pentane chain to an alcohol and then to a carboxyl group was the primary pathway. These metabolites were then further conjugated to either sulfate or glucuronide. The metabolic profile was altered at the higher dose level with a shift to a greater percentage of the alcohol in comparison to the carboxyl containing metabolite. The treatment with the labeled triazole moiety resulted in largely the same metabolic profile except for the recovery of labeled triazole in the urine.
...Rats were treated with tebuconazole labelled with 14C either in the phenyl ring or in the 3,5-triazole ring, with or without pretreatment with unlabelled compound, the main metabolites were the oxidation products of one of the methyl groups of the tertiary butyl moiety, i.e. the alcohol and the carboxylic acid. Metabolism in female animals resulted preferentially in simple oxidation products (eg, hydroxy and carboxy metabolites) and then conjugation to the glucuronide and sulfate, with only minor cleavage of the triazole moiety. In male animals, the primary oxidation products were further oxidized to triol and keto acid derivatives; in addition, cleavage of triazole occurred, as indicated in trials with triazole-labelled compound. The free triazole accounted for about 5% in the urine of the males and 1.5% in that of females. Parent compound was found in only minor amounts.
In a study /with/ lactating goats, the metabolic pathway was similar to that found in rats. The major metabolite identified was the tert-butyl alcohol derivative and its conjugate; the parent compound was also found.
In a study /with/ laying hens ... , hydroxylation of the tert-butyl group followed by conjugation to the sulfate was the major metabolic pathway.

Toxicity Data
LC50 (rat) = 820 mg/m3/4h

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Non-Human Toxicity Values
LD50 Rat oral >5000 mg/kg
LD50 Mouse oral 1615 mg/kg
LD50 Rabbit oral >1000 mg/kg
LD50 Dog oral 625 mg/kg
For more Non-Human Toxicity Values (Complete) data for TEBUCONAZOLE (7 total), please visit the HSDB record page.

[1]. Azole affinity of sterol 14α-demethylase (CYP51) enzymes from Candida albicans and Homo sapiens. Antimicrob Agents Chemother. 2013 Mar;57(3):1352-60.

[2]. Kwon HC, et.al. Tebuconazole Fungicide Induces Lipid Accumulation and Oxidative Stress in HepG2 Cells. Foods. 2021 Sep 22;10(10):2242.

[3]. Lee WY, et.al. Tebuconazole Induces ER-Stress-Mediated Cell Death in Bovine Mammary Epithelial Cell Lines. Toxics. 2023 Apr 21;11(4):397.

[4]. Ben Othmène Y,et.al. Tebuconazole induces ROS-dependent cardiac cell toxicity by activating DNA damage and mitochondrial apoptotic pathway. Ecotoxicol Environ Saf. 2020 Nov;204:111040.

[5]. Yang JD, et.al. Effects of tebuconazole on cytochrome P450 enzymes, oxidative stress, and endocrine disruption in male rats. Environ Toxicol. 2018 Jun 19.

[6]. Ma F, et.al. Gestational exposure to tebuconazole affects the development of rat fetal Leydig cells. Chemosphere. 2021 Jan;262:127792.

1-(4-chlorophenyl)-4,4-dimethyl-3-(1H-1,2,4-triazol-1-ylmethyl)pentan-3-ol is a tertiary alcohol that is pentan-3-ol substituted by a 4-chlorophenyl, methyl, methyl, and a 1H-1,2,4-triazol-1-ylmethyl at positions 1, 4, 4 and 3 respectively. It is a member of monochlorobenzenes, a member of triazoles and a tertiary alcohol.

C16H22CLN3O

307.8184

307.145

107534-96-3

Tebuconazole-d9;1246818-83-6

86102

White to off-white solid powder

1.1±0.1 g/cm3

476.9±55.0 °C at 760 mmHg

102-105°C

242.2±31.5 °C

0.0±1.3 mmHg at 25°C

1.564

3.58

1

3

6

21

326

0

PXMNMQRDXWABCY-UHFFFAOYSA-N

InChI=1S/C16H22ClN3O/c1-15(2,3)16(21,10-20-12-18-11-19-20)9-8-13-4-6-14(17)7-5-13/h4-7,11-12,21H,8-10H2,1-3H3

1-(4-chlorophenyl)-4,4-dimethyl-3-(1,2,4-triazol-1-ylmethyl)pentan-3-ol

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 : ≥ 50 mg/mL (~162.43 mM)
H2O : ~0.1 mg/mL (~0.32 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.12 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 (8.12 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 (8.12 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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Solubility in Formulation 4: 20 mg/mL (64.97 mM) in 0.5% CMC-Na/saline water (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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