Absorption, Distribution and Excretion
Both compounds /SAN-6706 and norflurazon/ were readily absorbed from nutrient solution by cotton (Gossypium hirsutum Leguminatae "Coker 203"), corn (Zea mays Leguminatae "WF9") and soybean (Glycine max (Leguminatae) Merr. "Lee") plants. In corn and soybean plants, these compounds were translocated more rapidly and in greater amount than in cotton.
Female Sprague-Dawley-rats were administered single doses of 0, 2, or 110 mg/kg carbon-14 (C-14)-labeled norflurazon by gavage. Some of the rats given 2 mg/kg radiolabeled norflurazon had been maintained on a diet containing 2 mg/kg unlabeled norflurazon for 14 days previously. Other rats were administered 0 or 2 mg/kg C-14 labeled norflurazon intravenously (iv). Urine, feces, and expired air were collected for 4 days and analyzed for C-14 activity. ... The rats were killed after 4 days to determine the tissue distribution of C-14 activity. Cumulative urinary excretion of C-14 label ranged from 18.5 to 28.4% of the doses. The largest excretion was by rats dosed iv and the smallest by rats given the single 110 mg/kg dose. Cumulative fecal excretion of C-14 activity ranged from 65.3 to 79.5%. Rats given the 110 mg/kg dose excreted the most radiolabel and those given 2 mg/kg after 14 days of dietary treatment the least. Only 0.1% of the doses was eliminated in the expired air. Less than 1% of each dose was recovered in the tissues and carcass. Only the liver and kidney contained relatively high levels of C-14 activity...
(14)C 4-Chloro-5-dimethylamino-2(a,a,a-trifluroo-m-tolyl)-3(2H)-pyridazinone was added to solutions in Ehrlenmeyer flasks in which cranberry cuttings were propagated. Subsequently, leaf, shoot and root were analyzed. Within one day, norflurazon and an unidentified metabolite were detected in the roots. After 15 days, in addition to norflurazon, 4-chloro-5-amino-2-(a,a,a,-trifluoro-m- tolyl)-3(2H)-pyridazinone was identified in leaf shoot and root. When norflurazon was applied to the plants, 4-chloro-5-amino-2-(a,a,a,-trifluoro-m- tolyl)-3(2H)-pyridazinone and an unidentified metabolite were observed in leaf, stem and root after 8 days.

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Metabolism / Metabolites
Norflurazon was administered as single oral doses of 2 or 110 mg/kg, a single i.v. dose of 2 mg/kg, or a single oral dose of 2 mg/kg following administration of 2 ppm in animal diet for 14 days to separate groups of rats. In urine, between 18.5-28.4% of the administered dose was eliminated by 96 hours post-dose, and between 65.3-79.5% of the administered dose was eliminated in feces. Thirteen metabolites of norflurazon were isolated. There appear to be 4 pathways for norflurazon metabolism: N-demethylation; displacement of the chlorine atom by glutathione; glutathione attack on the aromatic ring; and replacement of the chlorine atom by hydrogen ... . An additional metabolism study was conducted to determine the presence of the sulfone metabolite in rat excreta after a single low oral dose of 1 mg/kg, or a single high oral dose of 100 mg/kg. The sulfone metabolite was detected in both urine and feces of dosed rats. In urine, the sulfone metabolite accounted for 0.03% of urinary radioactivity at the low dose, and 0.2% of urinary radioactivity at the high dose. The sulfone metabolite accounted for 0.3% of fecal radioactivity at the low dose, and for 0.1% of fecal radioactivity at the high dose.
4-Chloro-5-dimethylamino-2-(a,a,a-trifluoro-m- tolyl)-3(2H)-pyridazinone was not degraded to any great extent in cotton. In corn and soybean, significant amounts of the mono- and des-methyl derivatives were seen after 24 hr. Metabolism of norflurazone also was more rapidly in corn and soybean than in cotton.
(14)C 4-Chloro-5-dimethylamino-2(a,a,a-trifluroo-m-tolyl)-3(2H)-pyridazinone was added to solutions in Ehrlenmeyer flasks in which cranberry cuttings were propagated. Subsequently, leaf, shoot and root were analyzed. Within one day, norflurazon and an unidentified metabolite were detected in the roots. After 15 days, in addition to norflurazon, 4-chloro-5-amino-2-(a,a,a,-trifluoro-m- tolyl)-3(2H)-pyridazinone was identified in leaf shoot and root. When norflurazon was applied to the plants, 4-chloro-5-amino-2-(a,a,a,-trifluoro-m- tolyl)-3(2H)-pyridazinone and an unidentified metabolite were observed in leaf, stem and root after 8 days.
The metabolism of norflurazon was investigated in ... female Sprague-Dawley-rats administered single doses of 0, 2, or 110mg/kg carbon-14 (C-14) labeled norflurazon by gavage. Some of the rats given 2mg/kg radiolabeled norflurazon had been maintained on a diet containing 2 mg/kg unlabeled norflurazon for 14 days previously. Other rats were administered 0 or 2 mg/kg C-14 labeled norflurazon intravenously (iv).Urine, feces, and expired air were collected for 4 days and analyzed ... for norflurazon metabolites. ... Six urinary metabolites were detected. Except for rats given the 110mg/kg dose, norflurazon-sulfoxide (NFS) was identified as the most abundant metabolite, accounting for 24 to 39% of the doses. The most abundant metabolite excreted by 110mg/kg rats was not identified. Ten fecal metabolites were detected, with NFS again identified as the predominant metabolite. Less than 2% of each dose was excreted as unchanged norflurazon. The authors conclude that norflurazon when given orally to rats is metabolized extensively primarily by N-demethylation and conjugation with glutathione.
For more Metabolism/Metabolites (Complete) data for NORFLURAZON (6 total), please visit the HSDB record page.

Non-Human Toxicity Values
LD50 Rabbit percutaneous >20,000 mg/kg
LD50 Rat percutaneous >5000 mg/kg
LD50 Rat oral >8000 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 appears as colorless odorless crystals. Non corrosive. Used as an herbicide.
Norflurazon is a pyridazinone that is pyridazin-3(2H)-one which is substituted at positions 2, 4, and 5 by m-(trifluoromethyl)phenyl, chloro, and methylamino groups, respectively. A pre-emergence herbicide used to control grasses and broad-leafed weeds in a variety of crops. Not approved for use within the European Union. It has a role as a carotenoid biosynthesis inhibitor, a herbicide and an agrochemical. It is a pyridazinone, a member of (trifluoromethyl)benzenes, an organochlorine compound and a secondary amino compound.
Norflurazon is a pyridazinone herbicide used to control grass and broadleaf weeds. Norflurazon inhibits carotenoid synthesis, which causes chlorophyll depletion and inhibition of photosynthesis in plants. Norflurazon has low toxicity if individuals accidentally eat residues, and very low toxicity if it is inhaled or gets on skin.

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Mechanism of Action
/The authors/cloned and sequenced a gene, pds, from the cyanobacterium Synechococcus PCC7942 that is responsible for resistance to the bleaching herbicide norflurazon. A point mutation in that gene, leading to an amino acid substitution from valine to glycine in its polypeptide product, was found to confer this resistance. Previous studies with herbicide-resistant mutants have indicated that this gene encodes phytoene desaturase (PDS), a key enzyme in the biosynthesis of carotenoids. A short amino acid sequence that is homologous to conserved motifs in the binding sites for NAD(H) and NADP(H) was identified in PDS, suggesting the involvement of these dinucleotides as cofactors in phytoene desturation.
Acts as a plant pigment inhibitor /in target species/. ... Inhibits biosynthesis of carotenoids. Without carotenoid pigments to filter the light, photodegradation occurs, hence chlorosis in nontolerant 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.)