Triadimenol (6.25-125 μM) inhibits the growth of cranial nerves and ganglia when it is cultured in cell serum for 48 hours [1].

Animal/Disease Models: 9.5-day-old rat embryos[1]
Doses: 6.25-125 μM
Route of Administration: Incubated in rat serum for 48 hrs (hrs (hours))
Experimental Results: Specific cranial nerve and ganglion abnormalities were demonstrated.

Absorption, Distribution and Excretion
... 16 laying hens received [phenyl-(14)C]triadimefon at 28.7 ppm for three consecutive days in feed. Triadimefon was identified in fat and eggs (4-17% TRR) but was not detected in liver or muscle. Triadimenol and its related compounds were the major metabolites identified (totals of 41-49% TRR). The remainder of the radioactivity was identified as KWG 1342 and its related compounds (totals of 10-36% TRR), p-chlorophenol (liver and fat only at 2- 4% TRR), chlorophenoxytriazolyl acetic acid (muscle only at 3% TRR), and KWG 1323 (eggs and fat only at 3-5% TRR). /Triadimefon/
Single oral doses of 25 mg/kg /triadimenol/ were administered to rats. Label was fairly readily excreted (over 70% in a week). In males, label was distributed 30% in urine and 53% in feces: in females distribution was 40% and 35%, respectively. No activity was found in expired gases. The major identified band in urine and in feces was KWG 0519 acid (formed by oxidation of the isobutyl moiety of triadimenol]. KWG 0519 (two isomers are present) was more abundant in plasma and in liver than the original Bayleton. Prevalence of KWG 0519 isomers was particularly apparent in males.

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Metabolism / Metabolites
... In studies conducted with rat hepatic microsomes, triadimenol was identified as the major metabolite (approximately 80%) of triadimefon metabolism, and reduction of the carbonyl group in triadimefon occurred stereoselectively with preferential formation of the less toxic triadimenol B diastereomer...
Triadimefon, triadimenol, and other triazole fungicides are metabolized in animals and plants to form compounds containing the triazole moiety, including 1,2,4-triazole (free triazole), triazole alanine, and triazole acetic acid, which are also considered in this decision ...
... A lactating goat received [phenyl-(14)C]triadimefon at 86.4 ppm for three consecutive days in feed. Triadimefon was detected at low levels in milk and fat (<5% TRR) but was not detected in kidney, liver, or muscle. The major residue identified was KWG 1342 glucuronide (6-47% TRR). Triadimenol and its conjugates comprised a major portion of the residue in tissues and milk (totals of 9-42% TRR). The remainder of the radioactivity was identified as KWG 1323 glucuronide (19-22% TRR) and KWG 1342 (1-6% TRR) and its sulfate (1-15% TRR in tissues, 43% TRR in milk). /Triadimefon/
... 16 laying hens received [phenyl-(14)C]triadimefon at 28.7 ppm for three consecutive days in feed. Triadimefon was identified in fat and eggs (4-17% TRR) but was not detected in liver or muscle. Triadimenol and its related compounds were the major metabolites identified (totals of 41-49% TRR). The remainder of the radioactivity was identified as KWG 1342 and its related compounds (totals of 10-36% TRR), p-chlorophenol (liver and fat only at 2- 4% TRR), chlorophenoxytriazolyl acetic acid (muscle only at 3% TRR), and KWG 1323 (eggs and fat only at 3-5% TRR). /Triadimefon/

Toxicity Data
LC50 (rat) = 2,580 mg/m3

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Interactions
... Doses of 15 and 60 mg/kg /triadimenol/ potentiated the effect of amphetamine while doses of 12 to 48 mg/kg antagonized the reserpin response. Triadimenol also prolonged the hexobartital sleeping time at 15 and 60 mg/kg.
... Rats exposed to 48 mg/kg triadimenol elicited an excitatory effect. A comparison with caffeine (doses of 2.5 and 10 mg/kg) showed that the effect of 2.5 mg/kg caffeine corresponded approximately to that of 12 to 15 mg/kg KWG 0519, in the amphetamine potentiation test 2.5 mg/kg caffeine elicited a similar response as 4 mg/kg KWG 0519, while in the antagonism of ptosis 10 mg/kg caffeine and 12 mg/kg KWG 0519 were comparable. The noeffect dose was 1 mg/kg for caffeine. The findings of this study point to a potential for stimulation of Central Nervous System (CNS).

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Non-Human Toxicity Values
LD50 Rat (males) oral 689 mg/kg
LD50 Rat (females) oral 752 mg/kg
LC50 Rat inhalation > 1 mg/L over 4 hrs
LD50 Rat dermal > 5000 mg/kg
For more Non-Human Toxicity Values (Complete) data for Triadimenol (8 total), please visit the HSDB record page.

[1]. In vitro teratogenic potential of two antifungal triazoles: triadimefon and triadimenol. In Vitro Cell Dev Biol Anim. 2000 Feb;36(2):88-95.

Triadimenol is a member of the class of triazoles that is 3,3-dimethyl-1-(1,2,4-triazol-1-yl)butane-1,2-diol substituted at position O1 by a 4-chlorophenyl group. A fungicide for cereals, beet and brassicas used to control a range of diseases including powdery mildew, rusts, bunts and smuts. It has a role as an EC 1.14.13.70 (sterol 14alpha-demethylase) inhibitor, a xenobiotic metabolite and an antifungal agrochemical. It is an aromatic ether, a member of monochlorobenzenes, a conazole fungicide, a triazole fungicide, a secondary alcohol and a hemiaminal ether.
Triadimenol has been reported in Brassica napus with data available.
Triadimenol is a fungicide for cereals, beet and brassicas used to control a range of diseases including powdery mildew, rusts, bunts and smuts. Its mode of action is selective with curative, protective and eradicant action. It disrupts membrane function.

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Mechanism of Action
Triazole-derivatives alter the pharyngeal apparatus morphogenesis of rodent embryos cultured in vitro. The hindbrain segmentation and the rhombencephalic neural crest cell (NCCs) migration are altered by Fluconazole exposure in vitro. The aim of the present work is to identify if a common pathogenic pathway is detectable also for other molecules of this class of compounds. 9.5 days post coitum (d.p.c.) old rat embryos were exposed in vitro to the teratogenic concentrations of Flusilazole, Triadimefon and Triadimenol and cultured for 24, 48 or 60 hr. The expression and localization of Hox-b1 and Krox-20 proteins (used as markers for hindbrain segmentation) were evaluated after 24 hr of culture. The localization and distribution of NCC was evaluated after 24, 30 and 48 hr of culture. The morphology of the embryos was analyzed after 48 hr, while the branchial nerve structures were evaluated after 60 hr of culture. Hindbrain segmentation and NCC migration alteration as well as pharyngeal arch and cranial nerve abnormalities were detected after exposure of the tested molecules. A common severe teratogenic intrinsic property for the tested molecules of this chemical class has been found, acting through alteration of the normal hindbrain developmental pattern.
Triazole fungicide pesticides, in general, are believed to exhibit their fungicidal activity through an inhibition of ergosterol biosynthesis, leading to an inhibition of cell wall precursors. /Researchers/ evaluated the potential for 14 triazole fungicides and structurally related compounds ... /Research/ showed that of the chemicals tested, only triadimefon and triadimenol were able to induce hyperactivity /in the CNS/; none of the other triazoles or related compounds tested produced this effect. The author hypothesized that the ether oxygen component of the triadimenol and triadimefon molecules appears to be an important structural requirement for induction of hyperactivity in rats. As such, at this time, although the fungicidal activity of triadimefon and triadimenol may be through the inhibition of sterol synthesis, the primary mode of toxicity in mammals appears to be neurotoxicity mediated through an indirect monoaminergic mechanism that appears to be specific to triadimefon and triadimenol only./Triazole fungicides/
The mode of toxic action for triadimenol involves blocking the re-uptake of dopamine. These pesticides act as indirect dopamine agonists by binding to the dopamine transporter and increasing levels of synaptic dopamine.

C14H18CLN3O2

295.767

295.108

55219-65-3

Triadimenol-d4;2121989-56-6

41368

Colorless crystalline solid

1.2±0.1 g/cm3

465.4±55.0 °C at 760 mmHg

110ºC

235.3±31.5 °C

0.0±1.2 mmHg at 25°C

1.580

3.04

1

4

5

20

303

0

CC(C)(C)C(C(N1C=NC=N1)OC2=CC=C(C=C2)Cl)O

BAZVSMNPJJMILC-UHFFFAOYSA-N

InChI=1S/C14H18ClN3O2/c1-14(2,3)12(19)13(18-9-16-8-17-18)20-11-6-4-10(15)5-7-11/h4-9,12-13,19H,1-3H3

1-(4-chlorophenoxy)-3,3-dimethyl-1-(1,2,4-triazol-1-yl)butan-2-ol

UK 199 UK-199 Baytan Spinnaker UK199 TriadimenolSummit

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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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