Absorption, Distribution and Excretion
Compounds SAN-6706 and norfloxacin were rapidly absorbed from nutrient solutions by cotton (upland cotton, Coker 203 variety), maize (WF9 variety), and soybean (Lee variety) plants. In maize and soybean plants, the translocation rate and amount of these compounds were higher than in cotton. Female Sprague-Dawley rats were administered a single dose of carbon-14 (C-14)-labeled norfloxacin by gavage. Rats partially administered 2 mg/kg of radiolabeled norfloxacin had previously been fed a diet containing 2 mg/kg of unlabeled norfloxacin for 14 consecutive days. Other rats were intravenously (iv) administered 0 or 2 mg/kg of C-14-labeled norfloxacin. Urine, feces, and exhaled gases were collected for 4 days, and C-14 activity was analyzed. …Rats were sacrificed 4 days later to determine the tissue distribution of C-14 activity. The cumulative urinary excretion of the C-14 marker ranged from 18.5% to 28.4% of the administered dose. The highest excretion was observed in rats administered intravenously, with the lowest excretion observed in rats receiving a single 110 mg/kg dose. The cumulative fecal excretion of C-14 activity ranged from 65.3% to 79.5%. Rats in the 110 mg/kg dose group excreted the most radiomarked marker, while rats in the 2 mg/kg dose group excreted the least after 14 days of dietary treatment. Only 0.1% of the dose was exhaled. Less than 1% of each dose was recovered from tissues and carcasses. Relatively high levels of C-14 activity were found only in the liver and kidneys…
Adding C-14 4-chloro-5-dimethylamino-2-(α,α,α-trifluoro-m-tolyl)-3(2H)-pyridazinone to the Ellenmeyer flask solution used for propagating cranberry cuttings. Subsequently, leaves, stems, and roots were analyzed. Within one day, fluazolidone and an unidentified metabolite were detected in the roots. After 15 days, 4-chloro-5-amino-2-(α,α,α-trifluoro-m-tolyl)-3(2H)-pyridazinone, in addition to fluazolidone, was also identified in the leaves, stems, and roots. Eight days after norfloxacin administration to the plants, 4-chloro-5-amino-2-(α,α,α-trifluoro-m-tolyl)-3(2H)-pyridazinone and an unidentified metabolite were detected in the leaves, stems, and roots.

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Metabolism/Metabolite
Rats were administered norfloxacin in different groups at a single oral dose of 2 or 110 mg/kg, a single intravenous dose of 2 mg/kg, or after 14 days of supplementation with 2 ppm norfloxacin in their diet, followed by a single oral dose of 2 mg/kg. Within 96 hours of administration, 18.5-28.4% of the administered dose was excreted in urine and 65.3-79.5% in feces. A total of 13 norfloxacin metabolites were isolated. The metabolic pathways of norfloxacin appear to be four: N-demethylation; glutathione substitution of chlorine atoms; glutathione attack on the aromatic ring; and chlorine atom substitution by hydrogen atoms… To determine the presence of sulfone metabolites in the excrement of rats following a single oral administration of a low dose of 1 mg/kg or a high dose of 100 mg/kg of norfloxacin, an additional metabolic study was conducted. The results showed that sulfone metabolites were detected in both the urine and feces of the administered rats. In urine, sulfone metabolites accounted for 0.03% of urinary radioactivity in the low-dose group and 0.2% in the high-dose group. In feces, sulfone metabolites accounted for 0.3% of fecal radioactivity in the low-dose group and 0.1% in the high-dose group.
4-Chloro-5-dimethylamino-2-(α,α,α-trifluoro-m-tolyl)-3(2H)-pyridazinone showed almost no degradation in cotton. In corn and soybean, significant amounts of monomethyl and demethylated derivatives were detected after 24 hours. Norfluprazole was also metabolized more rapidly in corn and soybean than in cotton.
14C 4-chloro-5-dimethylamino-2-(α,α,α-trifluoro-m-tolyl)-3(2H)-pyridazinone was added to an Ehrenmeyer flask solution used for propagating cranberry cuttings. Leaves, stems, and roots were subsequently analyzed. Within one day, fluazazole and an unidentified metabolite were detected in the roots. After 15 days, 4-chloro-5-amino-2-(α,α,α-trifluoro-m-tolyl)-3(2H)-pyridazinone was detected in the leaves, stems, and roots, in addition to fluazazole. When fluazolidone was applied to plants, 4-chloro-5-amino-2-(α,α,α-trifluoro-m-tolyl)-3(2H)-pyridazinone and an unidentified metabolite were observed in leaves, stems, and roots 8 days later. The metabolism of fluazolidone was investigated in female Sprague-Dawley rats administered by gavage with a single dose of 0, 2, or 110 mg/kg of carbon-14 (C-14)-labeled fluazolidone. Some rats had been fed a diet containing 2 mg/kg of unlabeled norfloxacin for 14 consecutive days prior to treatment with 2 mg/kg of radiolabeled norfloxacin. Other rats were intravenously injected with 0 or 2 mg/kg of C-14-labeled norfloxacin. Urine, feces, and exhaled breath were collected from the rats for 4 days, and norfloxacin metabolites were analyzed. …Six urinary metabolites were detected. Except for the 110 mg/kg dose group, norfloxacin sulfoxide (NFS) was identified as the most abundant metabolite, accounting for 24% to 39% of the total dose. The most abundant metabolite excreted by rats in the 110 mg/kg dose group was not identified. Ten fecal metabolites were detected, with NFS again identified as the major metabolite. Less than 2% of norfloxacin was excreted unchanged in any dose group. The authors conclude that after oral administration of norfloxacin, rats undergo extensive metabolism primarily through N-demethylation and binding to glutathione.
For more complete metabolite/metabolite data on norfloxacin (6 metabolites in total), please visit the HSDB record page.

Non-Human Toxicity Values
Rabbit dermal LD50 >20,000 mg/kg
Rat dermal LD50 >5,000 mg/kg
Rat oral LD50 >8,000 mg/kg

[1]. Evidence that norflurazon affects chloroplast lipid unsaturation in soybean leaves (Glycine max L.). J Agric Food Chem. 2009 Dec 9;57(23):11434-40.

Norflurazon is a colorless, odorless, and non-corrosive crystalline powder used as a herbicide. Norflurazon is a pyridazinone herbicide with the structure pyridazin-3(2H)-one, substituted at positions 2, 4, and 5 with m-trifluoromethylphenyl, chlorine, and methylamino, respectively. It is a pre-emergence herbicide used to control grassy and broadleaf weeds in various crops. It is not approved for use in the European Union. It has a dual function as a carotenoid biosynthesis inhibitor, herbicide, and agrochemical. It is a pyridazinone compound belonging to the trifluoromethylbenzene class, organochlorine compounds, and secondary amino compounds. Norflurazon is a pyridazinone herbicide used to control grassy and broadleaf weeds. Norflurazon inhibits carotenoid synthesis, leading to chlorophyll depletion and thus inhibiting plant photosynthesis. If ingested accidentally, Norflurazon residues have low toxicity; if inhaled or come into contact with the skin, their toxicity is extremely low.

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Mechanism of Action
/Authors/ The pds gene, responsible for resistance to the bleaching herbicide norfluront, was cloned and sequenced from the cyanobacterium Synthocodile PCC7942. The study found that a point mutation in this gene leads to the substitution of glycine for valine in its polypeptide product, thus conferring this resistance. Previous studies on herbicide-resistant mutants have shown that this gene encodes phytosterol dehydrogenase (PDS), a key enzyme in carotenoid biosynthesis. A short amino acid sequence homologous to the conserved motifs of NAD(H) and NADP(H) binding sites was identified in PDS, indicating that these dinucleotides participate as cofactors in the dehydrogenation process of phytosterols.
It functions as a phytopigment inhibitor (in the target species)...inhibiting carotenoid biosynthesis. Due to the lack of carotenoid pigments to filter light, photodegradation occurs, leading to yellowing in intolerant plants.

C12H9CLF3N3O

303.66

303.038

27314-13-2

33775

Off-white to light yellow solid powder

1.5±0.1 g/cm3

345.2±52.0 °C at 760 mmHg

184ºC

162.6±30.7 °C

0.0±0.8 mmHg at 25°C

1.567

2.45

1

6

2

20

461

0

NVGOPFQZYCNLDU-UHFFFAOYSA-N

InChI=1S/C12H9ClF3N3O/c1-17-9-6-18-19(11(20)10(9)13)8-4-2-3-7(5-8)12(14,15)16/h2-6,17H,1H3

4-chloro-5-(methylamino)-2-(3-(trifluoromethyl)phenyl)pyridazin-3(2H)-one

H 52143 Evital ZorialSolicamH-9789H-52143 H9789H 52143H 9789H52143Monometflurazon Telok

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.)