Absorption, Distribution and Excretion
Two Cr1:CD rats (half male and half female) were administered 5 or 60 mg/kg of Triazole-14C-ASC-66811 (M14360) (radiochemical purity: >99%, specific activity: 42 mCi/mmol) by gavage. The specific activity of the administered formulation was adjusted using unlabeled ASC-66811 (purity: 99.7%). Urine, carbon dioxide, and fecal samples were collected at specified time intervals within 168 hours post-administration. The distribution of the radiolabeled substance in tissues was assessed 168 hours post-administration. Urinary excretion was the primary route, with 79% to 95% of the administered radiolabeled substance recovered in urine. 12% to 16% of the radiolabeled substance was recovered in feces. At lower dose levels, 61% of the administered dose was excreted within 24 hours in males and 27% in females. At higher dose levels, 28% and 8% of the administered dose were excreted within 24 hours in males and females, respectively. The recovery rates of the radiolabeled radionuclide in exhaled breath were 0.13% to 0.23% of the administered dose at both dose levels. The residual radiolabeled radionuclide in tissues was 0.7% to 1.9% of the administered dose. No radiolabeled radionuclide remained in specific tissues 7 days after administration. Two Cr1:CD rats (half male and half female) were administered 5 or 60 mg/kg of [U-14C-phenyl]-ASC-66811 (M14360) (radiochemical purity: 99.3% (TLC), 99.0% (HPLC)) by gavage. The specific activity of the administered formulation was adjusted using unlabeled ASC-66811 (purity: 94.0%). Urine, carbon dioxide, and fecal samples were collected at specified time intervals within 168 hours after administration. The distribution of the radiolabeled radionuclide in tissues was assessed 168 hours after administration. Urinary excretion is the primary route of recovery, with 70% to 79% of the administered radiolabeled material recovered in urine. 21% to 32% of the radiolabeled material is recovered in feces. At lower dose levels, male and female rats excrete 70% and 57% of the administered dose, respectively, within 24 hours post-administration. At higher dose levels, male and female rats excrete 64% and 21% of the administered dose, respectively, within 24 hours post-administration. Very little radiolabeled material is recovered in exhaled air. Less than 1% of the administered dose remains in tissues. Seven days post-administration, the kidneys are the primary site of radiolabeled material recovery. Three Cr1:CD BR rats per group (each sex per group) were administered 5 or 60 mg/kg of (14C)-phenyl M 14360 (radiochemical purity: 96.90%, specific activity: 37.35 mCi/mmol) by gavage. The specific activity of the administered formulation was adjusted using unlabeled M 14360 technical-grade radioactive material (purity: 97.6%). Each animal (one male and one female) received only the excipient. Blood samples were collected from each study animal at specific time points following administration. The recovered radiolabeled material in each sample was determined by burning the samples and recovering the radiolabeled carbon dioxide, followed by analysis using liquid scintillation counting. Since the highest radioactivity level was recorded at the first sampling time point for each treatment group, the maximum blood concentration of the radiolabeled material could not be determined. The half-life of the radiolabeled material in blood was comparable across all treatment groups, with a mean half-life of 16.3 hours. Similarly, the elimination rate was comparable, with a mean of 0.044 ng equivalents/g/hour. Five Cr1:CD BR rats per group (each sex per group) were administered (14C)-phenyl M14360 (radiochemical purity: 97.99%, specific activity: 37.33 mCi/mmol) by gavage at doses of 5 or 60 mg/kg. The specific activity of the administered formulation was adjusted using unlabeled M14360 (purity: 97.6%). Two animals per sex were administered the excipient only. Urine, fecal, and cage cleaning fluid samples were collected from each group at specified time intervals following administration. Animals were sacrificed 72 hours after administration. The time to peak plasma concentration of the radiolabeled drug was 1.2 hours in the male group (5 mg/kg) and 19.2 hours in the female group (60 mg/kg). The plasma half-life was approximately 15 hours in all treatment groups. Urine was the primary route of excretion, with 62% to 70% of the administered dose recovered in urine and cage flushing fluid in both dose groups 72 hours post-administration. 25% to 36% of the dose was recovered in feces. 2.8% to 5.8% of the administered dose was recovered in tissues 72 hours post-administration. The gastrointestinal tract and liver were the primary sites of recovery. For more complete data on absorption, distribution, and excretion of tetrazolium (10 in total), please visit the HSDB record page. Metabolites/Metabolites: Three Sprague-Dawley rats of each sex were administered 1.25 mg/kg of (14C-U-triazolyl)tetrazole (radiochemical purity: 96.34%, specific activity: 41.72 μCi/mg) by gavage. The specific activity of the administered formulation was adjusted to 50 μCi/kg using unlabeled tetrazolium. Urine and feces were collected at specific time intervals within 72 hours post-administration. Urine was the primary route of excretion, with 71% and 62% of the administered dose recovered in urine in males and females, respectively. Additionally, 19% and 26% of the administered dose were recovered in feces in males and females, respectively. The main metabolite recovered in urine was triazole (64% in males and 41% in females). β-glucuronidase-mediated hydrolysis in urine samples did not significantly alter the metabolic profile. Unmetabolized tetrazolone was the main radiolabeled metabolite recovered in female feces, accounting for 8.8% of the administered dose. The main metabolite in male feces was M14360-DCP-3OH, accounting for 3.5% of the administered dose, followed by triazole (1.9%) and M14360-DCP-5OH (1.2%). In the experimental appendix, M14360-DFA was detected in the urine of female rats. The recovery amount was 1.2% of the administered dose.
In both single-dose and multiple-dose regimens, urine and fecal samples were collected within 48 hours following gavage administration of 5 or 60 mg/kg of (14C)-phenyl M14360 (radiochemical purity: 97.99%, specific activity: 37.33 mCi/mmol) to male and female Cr1:CD BR rats, and the radiolabeled metabolites were analyzed by GC/MS. Oxidation and reduction of the parent compound resulted in the recovery of M14360 acid in the urine and M14360 alcohol in the feces of both male and female rats under both dosing regimens and doses. Glutathione replaced the triazole ring in the parent compound and was subsequently metabolized to yield sulfoxide (P1) and 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. Other metabolites P2 and P3 were recovered in urine, and P5 was isolated in feces. The structures of these fractions have not been elucidated. Unidentified radiolabeled fractions accounted for 15% to 33% of the administered dose at both treatment levels under both regimens. ... Triazoles were the major metabolites identified in urine and feces. M-14360 acid and small amounts of the metabolite M-14360 alcohol and its glucuronide conjugate (M3) were isolated in urine. Small amounts of the parent compound M-14360, the acid, and the alcohol were isolated in feces. ... Tetrazoazole can generate 1,2,4-triazole (T), triazolyl alanine (TA), triazolyl acetic acid (TAA), and triazolyl hydroxypropionic acid (THP). For more complete metabolite/metabolite data on tetrazoazole (6 metabolites in total), please visit the HSDB record page.

Non-Human Toxicity Values
LD50 (Male rat): Oral administration 1030 mg ai/kg body weight LD50 (Female rat): Oral administration 1248 mg ai/kg body weight

[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 triazole compound with the structure 1,2,4-triazole substituted at position 1 by 2-(2,4-dichlorophenyl)-3-(1,1,2,2-tetrafluoroethoxy)propyl. It belongs to the triazole, dichlorobenzene, ether, and organofluorine compounds classes. Tetrazol is a liquid fungicide used to control Cercospora leaf spot 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.)