Absorption, Distribution and Excretion
Oral administration of hexaazine has not been shown to preferentially accumulate in any tissue. /Dosage not specified/ …Hexaazine was added to dairy cow feed at 0, 1, 5 or 25 ppm for 30 days. …No residues were detected in milk, fat, liver, kidney or lean meat. …The treatment methods for three groups of male and female Sprague Dawley rats were as follows: (1) Group A received a single low dose of (14)C-hexaazine (14 mg/kg) by gavage without pretreatment (treated with non-radioactive hexaazine); (2) Group B received a single low dose of (14)C-hexaazine (14 mg/kg) by gavage after three weeks of pretreatment with 100 ppm non-radioactive hexaazine; (3) Group C rats received a single high dose of (14)C-hexaazine (1000 mg/kg) by gavage without pretreatment. Hexazinone is rapidly metabolized via hydroxylation and demethylation and excreted in urine and feces over a test period of 3 to 6 days. Approximately 77% and 20% (dose) of (14)C-hexazinone were excreted in urine and feces, respectively. Almost all radioactive material was recovered within 24 hours of administration. Very low levels of radioactive material (approximately 0.2% of the dose) were detected in the gastrointestinal tract, skin, organs (heart, lungs, liver, spleen, kidneys, brain, and testes or ovaries), muscle, fat, and blood. Male rats were fed 2500 ppm (125 mg/kg) hexazinone in their diet for 17 days. Subsequently, the subjects received a single injection of 18.3 mg/300 g (61 mg/kg) of (14)C-labeled hexazinone. Hexazinone was rapidly absorbed within 72 hours, with 61% detected in urine and 32% in feces. Trace amounts were detected in the gastrointestinal tract (0.6%, tissue not specified) and exhaled air (0.08%). For more complete data on the absorption, distribution, and excretion of hexazinones (8 in total), please visit the HSDB record page. The major metabolites of hexazinones in rat urine include: 3-(4-hydroxycyclohexyl)-6-(dimethylamino)-1-methyl-1,3,5-triazin-2,4-(1H,3H)-dione (metabolite A); 3-cyclohexyl-6-(methylamino)-1-methyl-1,3,5-triazin-2,4-(1H,3H)-dione (metabolite B); and 3-(4-hydroxycyclohexyl)-6-(methylamino)-1-methyl-1,3,5-triazin-2,4-(1H,3H)-dione (metabolite C). The detection rates of these metabolites in urine were 46.8%, 11.5%, and 39.3%, respectively. The main metabolites in feces were A (26.3%) and C (55.2%). The levels of hexaazinone, which was not detected in either urine or feces, were both below 1%.

Toxicity Summary
Identification and Uses: Hexazinone is a white crystalline solid used as a herbicide. Human Exposure and Toxicity: A 26-year-old female experienced vomiting within 24 hours after inhaling hexazinone dust. Animal Studies: In a 10-day study, male rabbits were percutaneously treated with hexazinone for 6 hours daily at doses of 70 or 680 mg/kg/day without any signs of skin irritation or toxicity. A trend toward increased serum alkaline phosphatase (SAP) and serum alanine aminotransferase (SGPT) activities was observed. Hexazinone caused severe eye irritation in rabbits. The only detectable difference was a slightly lower growth curve in rats fed 5000 ppm hexazinone compared to the control group. Extending the feeding period to 2 years resulted in weight loss in male rats fed 2500 ppm and female rats fed 1000 or 2500 ppm. All other response parameters, including tumor type and incidence, were similar between the experimental and control groups. After 8 weeks of administration at concentrations up to 10,000 ppm, only the highest concentration group of mice showed an increase in liver weight, with no other changes observed. Two years of administration at 200, 2500, or 10,000 ppm resulted in tail tip detachment, and mice administered 10,000 ppm showed an increase in liver weight. Mice administered 2500 or 10,000 ppm showed central lobular hepatocyte hypertrophy and an increase in proliferative nodules. No evidence of tumorigenicity was observed. Dogs administered 5000 ppm hexaazine for 90 consecutive days showed slower weight gain and clinical signs such as enzymatic changes suggestive of liver damage. However, microscopic examination of the liver revealed no abnormalities, and dogs administered 200 ppm or 1000 ppm showed no significant difference from the control group. No teratogenic effects were observed in rats and rabbits, and the reproductive capacity of rats administered up to 2500 ppm hexaazine for three generations was not affected. No carcinogenicity was detected in rat pups fed up to 5000 ppm hexaazinone for two years. Similarly, no increased tumor incidence was observed in mice fed up to 10000 ppm hexaazinone. At concentrations up to 7000 μg/plate, hexaazinone was negative for mutagenicity testing against Salmonella typhimurium strains TA 1535, TA 1537, TA 1538, TA 98, and TA 100. Ecotoxicity studies: Two bird breeding studies showed that the no observed effect concentration (NOEC) in quail was < 100 ppm, while the NOEC in mallards was > 1000 ppm. Signal crayfish showed higher sensitivity to hexaazinone than fish and could serve as a biological indicator of environmental pollution. The ability of hexaazinone to control aquatic weeds was tested at a concentration of 1.0 ppm in a 0.08 hectare pond. Within 5 days post-treatment, dissolved oxygen decreased from 8.0 ppm to 0.2 ppm, which appears to be the cause of the fish mortality observed 4 days post-treatment.

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Non-human toxicity values
Oral LD50 in rats: 860 mg/kg
Oral LD50 in rats: 1690 mg/kg
Dermal LD50 in rats: 5278 mg/kg
Oral LD50 in guinea pigs: 860 mg/kg
For more complete non-human toxicity data on hexaquinones (9 in total), please visit the HSDB records page.

[1]. Hexazinone.From Wikipedia.

Hexazinone is a white crystalline solid, corrosive and irritating, used as a herbicide. Hexazinone belongs to the 1,3,5-triazine class of compounds. It is an organic compound used as a broad-spectrum herbicide. It is a colorless solid with some solubility in water, but high solubility in most organic solvents except alkanes. As a triazine herbicide, it is manufactured by DuPont under the trade name Velpar. Mechanism of Action: Inhibits photosynthesis in 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.)