Absorption, Distribution and Excretion
Orally administered hexazinone has not been demonstrated to accumulate preferentially in any tissue. /Dose not specified/
... Hexazinone was given in the diet at 0, 1, 5, or 25 ppm to /dairy cows/ for 30 days. ... No detectable residues /were noted/ in milk, fat, liver, kidney or lean muscle.
...Three groups of male and female Sprague Dawley rats were treated as follows: (1) Group A received a single intragastric low dose of (14)C-hexazinone (14 mg/kg) without preconditioning (treatment with non-radioactive hexazinone); (2) Group B received a single intragastric dose of (14)C-hexazinone (14 mg/kg) after three weeks of preconditioning with 100 ppm of non-radioactive hexazinone in the diet; and (3) Group C received a single intragastric high-dose of (14)C-hexazinone (1000 mg/kg) without preconditioning. Hexazinone was rapidly metabolized by hydroxylation and demethylation, and eliminated by the rats in urine and feces during the 3 to 6-day testing periods. About 77% and 20% (of the administered dose) of (14)C-hexazinone was excreted in urine and feces, respectively. Practically all radioactivity was recovered in the first 24 hours after treatment. Very low levels of radioactivity (about 0.2% of the administered dose) were detected in the G.I. tract, hide, organs (heart, lungs, liver, spleen, kidneys, brain, and testes or ovaries), muscle, fat and blood.
/Male rats were/ ... administered 2,500 ppm (125 mg/kg) hexazinone in the diet ... for 17 days. This was followed by a single dose of 18.3 mg/300 g (61 mg/kg) (14)C-labeled hexazinone. The hexazinone was rapidly absorbed within 72 hours, with 61% detected in the urine and 32% in the feces. Trace amounts were found in the gastrointestinal tract (0.6%, tissues not specified) and expired air (0.08%).
For more Absorption, Distribution and Excretion (Complete) data for Hexazinone (8 total), please visit the HSDB record page.

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Metabolism / Metabolites
Major urinary metabolites of hexazinone in rats /includes the following/: 3-(4-hydroxycyclohexyl)-6-(dimethylamino)-1-methyl-1,3,5-triazine- 2,4-(1H,3H)-dione (metabolite A); 3-cyclohexyl-6-(methylamino)-1-methyl- 1,3,5-triazine-2,4-(1H,3H)-dione (metabolite B); and 3-(4-hydroxycyclohexyl)-6- (methylamino)-1-methyl-1,3,5-triazine-2,4-(1H,3H)-dione (metabolite C). The percentages of these metabolites detected in the urine were 46.8, 11.5 and 39.3%, respectively. The major fecal metabolites ... were A (26.3%) and C (55.2%). Less than 1% unchanged hexazinone was detected in the urine or the feces.

Toxicity Summary
IDENTIFICATION AND USE: Hexazinone is a white crystalline solid. It is used as an herbicide. HUMAN EXPOSURE AND TOXICITY: A 26-year-old woman inhaled hexazinone dust. Vomiting occurred within 24 hours. ANIMAL STUDIES: In a 10-day study dermal application of hexazinone for 6 hours/day for 10 days to male rabbits at 70 or 680 mg/kg/day resulted in no signs of skin irritation or toxicity. A trend toward elevated serum alkaline phosphatase (SAP) and serum glutamic pyruvic-transaminase (SGPT) activities was observed. Severe ocular irritant in rabbits. Rats fed 5000 ppm had growth curves slightly inferior to those of controls as the only detectable difference. Extending the feeding period to 2 yr produced decreased body weights in males fed 2500 ppm and in females fed either 1000 or 2500 ppm. All other indices of response, including the type and incidence of tumors, were similar in the test and control rats. Mice after 8 wk feeding up to 10,000 ppm produced increased liver weight only at the highest level without any other changes. 2 yr feeding of either 200, 2500, or 10,000 ppm resulted in sloughing of the distal tip of the tail and increased liver weights among mice fed 10,000 ppm. Hypertrophy of centrilobular hepatocytes and hyperplastic nodules were increased in mice fed either 2500 or 10,000 ppm. No evidence of a tumorigenic response was evident. Dogs fed 5000 ppm for 90 days had decreased rate of body weight gain with clinical signs of enzyme changes suggestive of liver damage. Microscopic examination of the liver failed to reveal any alterations and dogs fed 200 or 1000 ppm were indistinguishable from controls. No evidence of a teratogenic effect was seen in either rats or rabbits and reproduction capacity in rats fed up to 2500 ppm for three generations was unaffected. No carcinogenicity was detected among pups of rats fed up to 5000 ppm for 2 years. Similarly, no increase in tumors was produced by feeding up to 10,000 ppm hexazinone to mice. Hexazinone tested negative for mutagenicity in Salmonella typhimurium strains TA 1535, TA 1537, TA 1538, TA 98 and TA 100 at concentrations up to 7,000 ug/plate. ECOTOXICITY STUDIES: Two avian reproduction studies conducted show that the No Observed Effect Concentration (NOEC) for the bobwhite quail is <100 and for the mallard duck is >1000 ppm. Signal crayfish is more sensitive than the fish for hexazinone, and can be used as a bio-indicator of environmental contamination. Hexazinone was tested for its ability to control aquatic weeds when applied at 1.0 ppm in a 0.08 hectare pond. Dissolved oxygen declined from 8.0 ppm to 0.2 ppm within 5 days after treatment and appeared to be the cause of fish mortality observed 4 days post treatment.

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Non-Human Toxicity Values
LD50 Rat oral 860 mg/kg
LD50 Rat oral 1690 mg/kg
LD50 Rat dermal 5278 mg/kg
LD50 Guinea pig oral 860 mg/kg
For more Non-Human Toxicity Values (Complete) data for Hexazinone (9 total), please visit the HSDB record page.

[1]. Hexazinone.From Wikipedia.

Hexazinone is a white crystalline solid. Corrosive eye irritant. Used as an herbicide.
Hexazinone is a member of 1,3,5-triazines.
Hexazinone is an organic compound that is used as a broad spectrum herbicide. It is a colorless solid. It exhibits some solubility in water but is highly soluble in most organic solvents except alkanes. A member of the triazine class herbicides, it is manufactured by DuPont and sold under the trade name Velpar.

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Mechanism of Action
Inhibition of photosynthesis at photosystem II.

C12H20N4O2

252.3128

252.158

51235-04-2

Hexazinone-d6;1219804-22-4

39965

White to off-white solid powder

1.3±0.1 g/cm3

332.8±25.0 °C at 760 mmHg

97-100.5ºC

155.1±23.2 °C

0.0±0.7 mmHg at 25°C

1.612

1.85

0

2

2

18

386

0

CAWXEEYDBZRFPE-UHFFFAOYSA-N

InChI=1S/C12H20N4O2/c1-14(2)10-13-11(17)16(12(18)15(10)3)9-7-5-4-6-8-9/h9H,4-8H2,1-3H3

3-cyclohexyl-6-(dimethylamino)-1-methyl-1,3,5-triazine-2,4-dione

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.)