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
Rapidly absorbed and excreted. Completely eliminated by 96 hrs. Extensively metabolized prior to excretion. Metabolic patterns similar for both sexes. Disposition & metabolism after pulse administration is linear over dose range. ... Elimination of label from plasma biphasic and evenly distribution between urine and feces. No tissue accumulation after 96 hours. At least 7 major metabolites recovered and identified. Highest amounts of radioactivity found in liver, kidneys, large and small intestines. No tissue accumulation.

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Metabolism / Metabolites
1,2,4-Triazole (1,2,4-T); triazole alanine (TA); and triazole acetic acid (TAA) are common metabolites to the class of compounds known as triazoles. In plants, 1,2,4-T is rapidly conjugated with serine to form TA. The TA can then be oxidized to form TAA. The extent to which 1,2,4-T, TA, and/or TAA forms in a given plant or animal is primarily dependent on the parent triazole-derivative fungicide. Across the various parent compounds, maximum formation of 1,2 4-T in plants ranges from 0% of the total radioactive residue (TRR) to 17% TRR, with the majority of compounds yielding 1,2,4-T at around 5-10% TRR. In rats, goats, and hens, maximum 1,2,4-T formation ranges from 0 to 77% TRR. Formation of 1,2,4-T in the rat is less than 20% TRR for the majority (approximately 80%) of the triazole-derivative fungicides for which data are available. Formation of TA ranges from 0 to 89% TRR in plants. Triazole acetic acid formation in plants ranges from 0 to 76% TRR. Triazole alanine and triazole acetic acid have generally not been found to be significant metabolites in rats, lactating goats, or laying hens. The exception to this appears to be fenbuconazole. In studies with radio-labeled fenbuconazole fed to goats and hens, TA formation ranges from 0 to 35% TRR; formation of TA from fenbuconazole was not noted in the rat metabolism studies. There is evidence from toxicological studies that there can be limited reduction of TA to 1,2,4-T following oral exposure to TA. /Triazole-derivative fungicide compounds/
Metabolism of two triazole-containing antifungal azoles was studied using expressed human and rat cytochrome P450s (CYP) and liver microsomes. Substrate depletion methods were used due to the complex array of metabolites produced from myclobutanil and triadimefon. Myclobutanil was metabolized more rapidly than triadimefon, which is consistent with metabolism of the n-butyl side-chain in the former and the t-butyl group in the latter compound. Human and rat CYP2C and CYP3A enzymes were the most active. Metabolism was similar in microsomes prepared from livers of control and low-dose rats. High-dose (115 mg/kg/day of triadimefon or 150 mg/kg/day of myclobutanil) rats showed increased liver weight, induction of total CYP, and increased metabolism of the two triazoles, though the apparent Km appeared unchanged relative to the control.
Myclobutanil metabolizes into 1,2,4-triazole, which has a lower acute toxicity than the parent compound (L2093). Organic nitriles are converted into cyanide ions through the action of cytochrome P450 enzymes in the liver. Cyanide is rapidly absorbed and distributed throughout the body. Cyanide is mainly metabolized into thiocyanate by either rhodanese or 3-mercaptopyruvate sulfur transferase. Cyanide metabolites are excreted in the urine. (L96)

Toxicity Summary
Organic nitriles decompose into cyanide ions both in vivo and in vitro. Consequently the primary mechanism of toxicity for organic nitriles is their production of toxic cyanide ions or hydrogen cyanide. Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected. Cyanide is also known produce some of its toxic effects by binding to catalase, glutathione peroxidase, methemoglobin, hydroxocobalamin, phosphatase, tyrosinase, ascorbic acid oxidase, xanthine oxidase, succinic dehydrogenase, and Cu/Zn superoxide dismutase. Cyanide binds to the ferric ion of methemoglobin to form inactive cyanmethemoglobin. (L97)

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

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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

Myclobutanil can cause developmental toxicity and male reproductive toxicity according to The Environmental Protection Agency (EPA).
Myclobutanil is a light yellow solid used as a fungicide.
2-(4-chlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)hexanenitrile is a nitrile that is hexanenitrile substituted at the 2-position by p-chlorophenyl and (1,2,4-triazol-1-yl)methyl groups. It is a nitrile, a member of triazoles and a member of monochlorobenzenes.
Myclobutanil is a triazole chemical used as a fungicide. It is a steroid demethylation inhibitor, specifically inhibiting ergosterol biosynthesis. Ergosterol is a critical 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.

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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.

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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.

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