Topramezone (5, 10, 20, 30, 45 mg/L; 24-96 hours) reduces the formation of C. vulgaris algal blooms by causing oxidative stress, which alters the shape of cells and their ability to photosynthesize [1]. Topramezone (20 mg/L; 24, 48, 72, and 96 hours) depletes the photosynthetic system by decreasing the amount of pigments involved in photosynthesis and causes a time-dependent rise in MDA and ROS (oxidative stress) [1]. Topramezone (20 mg/L; 96 hours) damages algal cell membranes and chloroplasts, impairing cell integrity and inducing death [1]. Topramezone (0.1 nM-0.1 mM; 30 min) has IC50s of 15 nM for setaria, 23 nM for Arabidopsis thaliana, and 180 nM for maize. It is selective and inhibits 4-HPPD (recombinase protein) activity in vitro [2]. Corn metabolizes topramezone (foliar spray; contains 0.29 µg [14C]topramezone; 24 and 48 hours) more quickly than weeds [2].

Absorption, Distribution and Excretion
Metabolism and Pharmacokinetics: Following a single oral dose of 14C-topramedone, absorption was rapid but limited, with peak plasma concentrations reached at 1 hour (the time point of first measurement). Oral absorption was estimated to be approximately 20% of the administered dose. The majority of the dose was excreted in feces (73–91% of the dose) and urine (8–29% of the dose) within 48 hours. /From Table/ [EPA; 40 CFR Part 180] Skin Penetration: The majority of the administered dose was not absorbed in each group (91.0–98.3% of the dose), and most of the unabsorbed material was recovered via skin flushing solutions (90.8–96.0% of the dose). Absorbed radioactivity was low, ranging from 0.16% to 2.60% of all exposure doses across all groups (data from Table) [EPA; 40 CFR Part 180]

Toxicity Summary
Topramedone has low acute toxicity via oral, dermal, or inhalation routes. It is mildly irritating to the eyes and skin but does not cause skin sensitization. After oral administration, topramedone is rapidly absorbed and excreted in urine and feces. Topramedone is an inhibitor of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD), which leads to elevated serum tyrosine levels. However, there are currently no data to determine the extent to which elevated tyrosine levels will cause harmful (adverse) reactions. Due to elevated tyrosine levels, topramedone has been shown to have adverse effects on the eyes, liver, kidneys, pancreas, and thyroid. Histopathological evaluation showed dose-dependent increases in adverse effects on the thyroid gland (follicular cell hyperplasia) in rats and dogs, the pancreas (diffuse degeneration) in rats, the liver (hepatocyte hypertrophy and focal necrosis) in rats and mice, and the eyes (chronic keratitis) in rats. Reproductive toxicity studies in rats did not reveal adverse reproductive effects; however, developmental toxicity studies in rats and rabbits showed an increased incidence of skeletal variations and alterations in the site of ossification. Animal studies have shown that skeletal variations are associated with 4-HPPD inhibitor herbicides (mesulfuron and isoxaflutole). Mutagenicity studies of topiramate and its major metabolites have not revealed any mutagenicity. In carcinogenicity studies in male and female rats, an increased incidence of thyroid follicular cell adenomas and adenomas and/or adenocarcinomas was observed. According to the U.S. Environmental Protection Agency's (EPA) Final Guidance for Carcinogen Risk Assessment issued on March 29, 2005, the EPA's Health Effects Division (HED) classifies topiramate as "not likely to be carcinogenic to humans at doses that do not alter thyroid hormone homeostasis in rats." The HED determined that since the no-observed-adverse-effects dose (NOAEL, 0.4 mg/kg/day) is not expected to alter thyroid hormone homeostasis or cause thyroid tumor formation, there is no need to quantify the human cancer risk.

[1]. Zhao F, et al. Evaluation of the toxicity of herbicide topramezone to Chlorella vulgaris: Oxidative stress, cell morphology and photosynthetic activity. Ecotoxicol Environ Saf. 2017 Sep. 143:129-135.
[2]. Grossmann K, et al. On the mechanism of action and selectivity of the corn herbicide topramezone: a new inhibitor of 4-hydroxyphenylpyruvate dioxygenase. Pest Manag Sci. 2007 May. 63(5):429-39.

Topramerone is an aromatic ketone with the structure phenyl-1H-pyrazol-4-yl ketone, where the pyrazol group is substituted with methyl and hydroxyl groups at positions 1 and 5, respectively, and the phenyl group is substituted with methyl, 4,5-dihydro-1,2-oxazol-3-yl, and methanesulfonyl groups at positions 2, 3, and 4, respectively. It is a potent inhibitor of 4-hydroxyphenylpyruvate dioxygenase (HPPD) and is rapidly metabolized into inactive substances by maize, thus being used as a herbicide for broadleaf weeds. It possesses multiple functions, including herbicide, agrochemical, EC 1.13.11.27 (4-hydroxyphenylpyruvate dioxygenase) inhibitor, and carotenoid biosynthesis inhibitor. It is a sulfone compound belonging to the isoxazole, aromatic ketone, and pyrazolone classes. Topramerone is currently being studied in the clinical trial NCT00559520 (The Role of Preoperative Oral Immunonutrition in Major Vascular Surgery).

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Mechanism of Action
Topramerone exhibits herbicidal activity against broadleaf and grass weeds. Its efficacy stems from the inhibition of 4-hydroxyphenylpyruvate dioxygenase (HPPD) in target plants. In sensitive plants, treatment disrupts carotenoid pigment formation, cell membrane structure, and photosynthesis.

C16H17N3O5S

363.38800

363.088

210631-68-8

11302979

Light beige liquid

1.5±0.1 g/cm3

590.5±60.0 °C at 760 mmHg

310.9±32.9 °C

0.0±1.7 mmHg at 25°C

1.670

0.96

1

7

4

25

752

0

Cc1c(ccc(c1C2=NOCC2)S(=O)(=O)C)C(=O)c3cnn(c3O)C

BPPVUXSMLBXYGG-UHFFFAOYSA-N

InChI=1S/C16H17N3O5S/c1-9-10(15(20)11-8-17-19(2)16(11)21)4-5-13(25(3,22)23)14(9)12-6-7-24-18-12/h4-5,8,17H,6-7H2,1-3H3

4-[3-(4,5-dihydro-1,2-oxazol-3-yl)-2-methyl-4-methylsulfonylbenzoyl]-2-methyl-1H-pyrazol-3-one

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.)