Absorption, Distribution and Excretion
Two Crl:CD rats/sex/group were dosed orally by gavage with 5 or 60 mg/kg of Triazole-14C-ASC-66811 (M14360) (radiochemical purity: >99%, specific activity: 42 mCi/mmole). Unlabelled ASC-66811 (purity: 99.7%) was used to adjust the specific activity of the dosing preparations. Urine, carbon dioxide, and fecal samples were collected at designated intervals up to 168 hours post-dose. The distribution of radiolabel in the tissues was examined at 168 hours post-dose. Excretion via the urine was the primary pathway with 79 to 95% of the administered radiolabel recovered in the urine. Twelve to 16% of the radiolabel was recovered in the feces. At the lower dosing level, 61 and 27% of the administered dose was excreted within the 1st 24 hours post-dose for the males and females, respectively. At the higher dose, 28 and 8% of the dose was excreted during the 1st 24 hours for the males and female, respectively. Recovery of the radiolabel in the exhaled air ranged from 0.13 to 0.23% of the administered dose for both dose levels. The residual radiolabel in the tissues ranged from 0.7 to 1.9% of the administered dose. The radiolabel was not sequestered in a particular tissue at 7 days post-dose.
Two Crl:CD rats/sex/group were dosed orally by gavage with 5 or 60 mg/kg of [U-14C-phenyl]-ASC-66811 (M14360) (radiochemical purity: 99.3% (TLC), 99.0% (HPLC)). Unlabelled ASC-66811 (purity: 94.0%) was used to adjust the specific activity of the dosing preparations. Urine, carbon dioxide, and fecal samples were collected at designated intervals up to 168 hours post-dose. The distribution of radiolabel in the tissues was examined at 168 hours post-dose. Excretion via the urine was the primary pathway with 70 to 79% of the administered radiolabel recovered in the urine. Twenty one to 32% of the radiolabel was recovered in the feces. At the lower dosing level, 70 and 57% of the administered dose was excreted within the 1st 24 hours post-dose for the males and females, respectively. At the higher dose, 64 and 21% of the dose was excreted during the 1st 24 hours for the males and female, respectively. Recovery of the radiolabel in the exhaled air was minimal. The residual radiolabel in the tissues constituted <1% of the dose. The kidneys were the primary site of recovery at 7 days post-dose.
Three Crl:CD BR rats/sex/group were dosed orally by gavage with 5 or 60 mg/kg of (14C)-Phenyl M 14360 (radiochemical purity: 96.90%, specific activity: 37.35 mCi/mmole). Unlabeled M 14360 technical (purity: 97.6%) was used to adjust the specific activity of the dosing preparations. One animal/sex was dosed with the vehicle alone. Blood was drawn at specified times post-dose from each of the study animals. The radiolabel recovered from each sample was determined by combustion of the sample and recovery of the radiolabeled carbon dioxide which was then analyzed by liquid scintillation counting. The maximal blood concentration of the radiolabel could not be determined because the highest level of radioactivity was recorded for the first sample time in each of the treatment groups. The reported half-lives for the radiolabel in the blood were comparable for all of the treatment groups with a mean for all of the groups of 16.3 hours. Likewise the rates of elimination were comparable with the mean value being 0.044 ng equivalents/g/hour.
Five Crl:CD BR rats/sex/group were dosed orally by gavage with 5 or 60 mg/kg of (14C)-Phenyl M 14360 (radiochemical purity: 97.99%, specific activity: 37.33 mCi/mmole). Unlabeled M 14360 (purity: 97.6%) was used to adjust the specific activity of the dosing preparations. Two animals/sex were dosed only with the vehicle. Urine, feces and cage wash samples were collected from each of the groups at designated time intervals after treatment. The animals were euthanized at 72 hours post-dose. The time-to-peak blood levels for the radiolabel ranged from 1.2 hours post-dose for the 5 mg/kg males to 19.2 hours post-dose for the 60 mg/kg females. The half-life in the blood was approximately 15 hours for all of the treatment groups. The urine was the primary pathway of excretion with 62 to 70% of the administered dose being recovered in the urine and cage wash by 72 hours post-dose for both treatment levels. The recovery in the feces from these groups ranged from 25 to 36%. At 72 hours post-dose, 2.8 to 5.8% of the administered dose was recovered in the tissues. The gastrointestinal tract and the liver were the primary sites of recovery.
For more Absorption, Distribution and Excretion (Complete) data for TETRACONAZOLE (10 total), please visit the HSDB record page.

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Metabolism / Metabolites
Three Sprague-Dawley rats/sex were dosed orally by gavage with 1.25 mg/kg of (14C-U-triazolyl) tetraconazole (radiochemical purity: 96.34%, specific activity: 41.72 uCi/mg). Unlabeled tetraconazole was used to adjust the specific acitivity of the dosing preparation to 50 uCi/kg. Urine and feces were collected at specific time intervals up to 72 hours post-dose. Urine was the primary route of excretion with 71 and 62% of the administered dose recovered there for the males and females, respectively. An additional 19 and 26% was recovered in the feces of the males and females respectively. The primary metabolite recovered in the urine was triazole (64 and 41% for the males and females, respectively). Beta-glucuronidase-mediated hydrolysis of the urine samples did not greatly alter the metabolic profile. Unmetabolized tetraconazole was the primary radiolabeled moiety recovered in the feces of the females, 8.8% of the administered dose. M14360-DCP-3OH was the primary metabolite in the feces of the males, 3.5% of the administered dose, followed by triazole (1.9%) and M14360-DCP-5OH (1.2%). In the Experimental Addendum..., M14360-DFA was identified in the urine of the female rats. This recovery constituted 1.2% of the administered dose.
Pooled urine and fecal samples derived from the first 48 hours post-dose of both single dose and multiple dose treatment regimens in which Crl:CD BR rats of both sexes were dosed orally by gavage with 5 or 60 mg/kg of (14C)-Phenyl M 14360 (radiochemical purity: 97.99%, specific activity: 37.33 mCi/mmole)... were analyzed for radiolabeled metabolites by means of GC/MS. Oxidation and reduction of the parent compound resulted in the recovery of the M 14360 acid in the urine and the M14360 alcohol in the feces of both sexes at both treatment levels for both treatment regimens. Displacement of the triazole ring from the parent compound by glutathione and subsequent metabolism resulted in the recovery of the sulfoxide (P1) and the N-acetylcysteine (P4) conjugates. P1, P4 and M 14360 acid were recovered in the urine. P4, M 14360 and M 14360 alcohol were recovered in the feces. Additional metabolites, P2 and P3, were recovered in the urine and P5 was isolated in the feces. The structures of these moieties were not elucidated. The unidentified radiolabeled moieties constituted 15 to 33% of the administered dose for both treatment levels under both treatment regimens.
... Triazole was the major metabolite identified in the urine and feces. In the urine M-14360 acid along with minor metabolite of M-14360 alcohol and its glucuronide conjugate (M3) were isolated. In the feces minor amounts of parent M-14360, the acid and alcohol were isolated. ...
Tetraconazole results in the formation of /1,2,4-triazole (T), triazolyl alanine (TA), triazolyl acetic acid (TAA)/ as well as /triazolyl hydroxypropionic acid/ (THP).
For more Metabolism/Metabolites (Complete) data for TETRACONAZOLE (6 total), please visit the HSDB record page.

Non-Human Toxicity Values
LD50 Rat (male) oral 1030 mg a.i./kg bw
LD50 Rat (female) oral 1248 mg a.i./kg bw

[1]. Enantioselective effects of the chiral fungicide tetraconazole in wheat: Fungicidal activity and degradation behavior. Environ Pollut. 2019;247:1-8.

[2]. Tetraconazole alters the methionine and ergosterol biosynthesis pathways in Saccharomyces yeasts promoting changes on volatile derived compounds. Food Res Int. 2020;130:108930.

1-[2-(2,4-dichlorophenyl)-3-(1,1,2,2-tetrafluoroethoxy)propyl]1,2,4-triazole is a member of the class of triazoles that is 1,2,4-triazole substituted at position 1 by a 2-(2,4-dichlorophenyl)-3-(1,1,2,2-tetrafluoroethoxy)propyl group. It is a member of triazoles, a dichlorobenzene, an ether and an organofluorine compound.
Tetraconazole is a liquid fungicide for control of Cercospora leafspot and powdery mildew on sugar beets.

C13H11CL2F4N3O

372.15

371.021

112281-77-3

80277

Colorless to light yellow viscous liquid

1.5±0.1 g/cm3

438.4±55.0 °C at 760 mmHg

Pour point 6 °C

219.0±31.5 °C

0.0±1.1 mmHg at 25°C

1.544

3.19

0

7

7

23

381

0

C1=CC(=C(C=C1Cl)Cl)C(CN2C=NC=N2)COC(C(F)F)(F)F

LQDARGUHUSPFNL-UHFFFAOYSA-N

InChI=1S/C13H11Cl2F4N3O/c14-9-1-2-10(11(15)3-9)8(4-22-7-20-6-21-22)5-23-13(18,19)12(16)17/h1-3,6-8,12H,4-5H2

1-[2-(2,4-dichlorophenyl)-3-(1,1,2,2-tetrafluoroethoxy)propyl]-1,2,4-triazole

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 : 125 mg/mL (335.89 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.59 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 20.8 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: ≥ 2.08 mg/mL (5.59 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 20.8 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: ≥ 2.08 mg/mL (5.59 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 20.8 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.)