Cell viability was decreased by myclobutanil to less than 50% at 100 ppm and less than 10% at 500 ppm. Fatty acid (FA)-induced steatosis was marginally but significantly elevated by myclobutanil at dosages ranging from 1 to 100 ppm. Anti-apoptotic indicators are considerably reduced by myclobutanil [1].

Absorption, Distribution and Excretion
Absorption and excretion are rapid. Complete elimination within 96 hours. Extensive metabolism prior to excretion. Similar metabolic patterns in both sexes. Distribution and metabolism following pulsed administration are linear within the dose range. …Elimination of the marker from plasma is biphasic, with uniform distribution in urine and feces. No tissue accumulation after 96 hours. At least 7 major metabolites were recovered and identified. Highest radioactivity was found in the liver, kidneys, large intestine, and small intestine. No tissue accumulation. Metabolites/Metabolites 1,2,4-triazole (1,2,4-T), triazole alanine (TA), and triazole acetic acid (TAA) are common metabolites of triazole compounds. In plants, 1,2,4-T rapidly binds to serine to form TA. TA can then be oxidized to TAA. The production of 1,2,4-T, TA, and/or TAA in a given plant or animal depends primarily on its parent triazole fungicide. Among different parent compounds, the maximum production of 1,2,4-T in plants ranges from 0% to 17% of the total radioactive residue (TRR), with most compounds producing approximately 5-10% of 1,2,4-T. In rats, goats, and chickens, the maximum production of 1,2,4-T ranges from 0% to 77% of the TRR. For most (approximately 80%) of the triazole fungicides with available data, the production of 1,2,4-T in rats is less than 20% of the TRR. TA production in plants ranges from 0% to 89% of the TRR. The production rate (TRR) of triazoleacetic acid in plants ranges from 0% to 76%. Triazole alanine and triazoleacetic acid are generally not found as important metabolites in rats, lactating goats, or laying hens. However, fenbuconazole appears to be an exception. In studies feeding goats and hens with radiolabeled fenbuconazole, the production rate (TRR) of triazoleacetic acid ranged from 0% to 35%; no production of triazoleacetic acid from fenbuconazole was observed in rat metabolic studies. Toxicological studies have shown that after oral administration of triazoleacetic acid, a small amount of triazoleacetic acid can be converted to 1,2,4-triazoleacetic acid. /Triazole Derivative Fungicide Compounds/
The metabolism of two triazole-containing antifungal azole compounds was studied using expressed human and mouse cytochrome P450 (CYP) and liver microsomes. Due to the numerous metabolites of tebuconazole and triazole, a substrate consumption method was used. Tebuconazole was metabolized faster than triazole, consistent with the metabolism of the n-butyl side chain in tebuconazole and the tert-butyl side chain in triazole. The highest CYP2C and CYP3A enzyme activities were observed in humans and rats. Metabolism in liver microsomes was similar in the control and low-dose groups of rats. In the high-dose groups (triazole 115 mg/kg/day or tebuconazole 150 mg/kg/day), rats showed increased liver weight, enhanced total CYP activity, and accelerated metabolism of both triazole compounds, but the apparent Km values appeared unchanged compared to the control group. Tebuconazole is metabolized to 1,2,4-triazole, which has lower acute toxicity than the parent compound (L2093). Organic nitriles are converted to cyanide ions in the liver by cytochrome P450 enzymes. Cyanide ions are rapidly absorbed and distributed throughout the body. Cyanide ions are primarily metabolized to thiocyanate by thiocyanate oxidase or 3-mercaptopyruvate thiotransferase. Cyanide metabolites are excreted in the urine. (L96)

Toxicity Summary
Organic nitriles can decompose into cyanide ions both in vivo and in vitro. Therefore, the main toxic mechanism of organic nitriles is the production of toxic cyanide ions, or hydrogen cyanide. Cyanide ions are inhibitors of cytochrome c oxidase in the fourth electron transport chain complex (located on the mitochondrial membrane of eukaryotic cells). It forms a complex with the ferric atom in this enzyme. The binding of cyanide ions to this cytochrome prevents electrons from being transferred from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted, and the cell can no longer perform aerobic respiration to produce ATP for energy. Tissues that rely primarily on aerobic respiration, such as the central nervous system and the heart, are particularly susceptible to this. Cyanide can also produce some toxic effects by binding to catalase, glutathione peroxidase, methemoglobin, hydrocobalamin, phosphatase, tyrosinase, ascorbic acid oxidase, xanthine oxidase, succinate dehydrogenase, and copper/zinc superoxide dismutase. Cyanide binds to the iron ions in methemoglobin to form inactive methemoglobin cyanide. (L97)

---

Toxicity Data
LC50 (Rat) > 5,000 mg/m3
LD50: 1.75 to 1.8 g/kg (Rat, oral) (L2093)

---

Non-human Toxicity Values
LD50 Rat (Male) Oral 1600 mg/kg
LD50 Rat (Female) Oral 2290 mg/kg

[1]. Stellavato A, et al. Myclobutanil worsens nonalcoholic fatty liver disease: An in vitro study of toxicity and apoptosis on HepG2 cells. Toxicol Lett. 2016 Nov 16;262:100-104

According to the U.S. Environmental Protection Agency (EPA), tebuconazole can cause developmental toxicity and male reproductive toxicity. Tebuconazole is a pale yellow solid used as a fungicide. 2-(4-chlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)hexanonitrile is a nitrile compound in which the 2-position of the hexanonitrile is replaced by a p-chlorophenyl group and a (1,2,4-triazol-1-yl)methyl group. It is a nitrile compound belonging to the triazole and monochlorobenzene classes. Tebuconazole is a triazole compound used as a fungicide. It is a steroid demethylation inhibitor that specifically inhibits the biosynthesis of ergosterol. Ergosterol is an important component of fungal cell membranes.

C15H17CLN4

288.77

288.114

88671-89-0

6336

Pale yellow solid.
Light yellow crystals

1.2±0.1 g/cm3

465.2±55.0 °C at 760 mmHg

63-68°C

235.2±31.5 °C

0.0±1.1 mmHg at 25°C

1.589

2.82

0

3

6

20

345

0

N#CC(CCCC)(CN1C=NC=N1)C1C=CC(Cl)=CC=1

HZJKXKUJVSEEFU-UHFFFAOYSA-N

InChI=1S/C15H17ClN4/c1-2-3-8-15(9-17,10-20-12-18-11-19-20)13-4-6-14(16)7-5-13/h4-7,11-12H,2-3,8,10H2,1H3

2-(4-chlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)hexanenitrile

HOE39304F; HOE 39304F; Myclobutanil

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 (~346.28 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.66 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.

---

Solubility in Formulation 2: ≥ 2.5 mg/mL (8.66 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.

---

View More

Solubility in Formulation 3: ≥ 2.5 mg/mL (8.66 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.

---

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