Absorption, Distribution and Excretion
Toxicokinetic studies in mice, rats, and rabbits showed that bentazon is rapidly and almost completely absorbed (>99%) via the oral route, reaching maximum plasma concentrations in approximately 15 minutes at low doses (4 mg/kg body weight) and in approximately 1 hour at high doses (200 mg/kg body weight). Absorption was not significantly different when administered as a sodium salt or free acid. No evidence of drug penetration into the central nervous system or spinal cord was found, and it was rapidly cleared from other tissues without any signs of bioaccumulation. The drug is almost completely excreted in the urine (approximately 91% excreted within 24 hours); after 5 days of administration, the drug content in feces was less than 2%, and in exhaled breath less than 0.02%. Very little radioactive material was excreted in bile. No significant differences in absorption and elimination were found among the different species studied (rats, rabbits, and mice).
The skin permeability of bentazon sodium salt was evaluated by applying a single topical application of approximately 4933, 49.3, or 8.22 μg/cm² of the active ingredient (prepared with BAS 351 32 H) to a layered skin membrane mounted on a Franz-type diffusion cell. Doses represented either the formulation concentrate or two representative spray diluents (1:100 and 1:600) for field use. Five diffusion cells were used for each dose. …It can be concluded that the in vitro skin permeability of the water-soluble (liquid) concentrate of bentazon sodium is appropriate as a percentage of absorbed dose. Considering that the amount of radiolabeled material remaining on the skin after washing (remaining skin and tape strips 3-6) can be absorbed, and combining this with the absorption detected in the receptor, the skin permeability of the concentrate is approximately 0.06%, the skin permeability of the 1:100 spray dilution is approximately 1.31%, and the skin permeability of the 1:600 dilution is approximately 1.23%. /Bentazapine Sodium/
This article presents a case of death due to suicidal bentazapine poisoning and describes the different analytical methods involved. A 56-year-old farmer was examined by his family doctor one hour after voluntarily ingesting 500 ml of Fighter (approximately 250 g of bentazapine). He had a Glasgow Coma Scale score of 15 and presented with shortness of breath, diarrhea, and vomiting. En route to the hospital by ambulance, he tossed and turned, sweated profusely, and suddenly developed respiratory distress, followed by heart failure. The patient died within 2 hours of ingestion. Blood and urine samples were collected shortly before death. The plasma and urine concentrations of bentazon were 1500 mg/L and 1000 mg/L, respectively. A 59-year-old woman intentionally ingested 100-200 mL of paraquat (containing approximately 50-100 g of bentazon) and was hospitalized two days later due to cardiac arrest. During this time, she experienced vomiting, urination, and diarrhea, accompanied by drowsiness and slurred speech. Analysis of biological samples collected during the autopsy revealed active metabolites of bentazon, alcohol, and citalopram. The plasma concentrations of bentazon, alcohol, and desmethylcitalopram were 625 mg/kg, 0.62 g/L, and 0.03 mg/kg, respectively. Metabolites/Metabolites: The metabolism of bentazon was investigated through multiple toxicokinetic studies following oral (rat and rabbit) or intravenous (mouse) administration… Bendasone is metabolized at a very low rate, with its parent compound being the main excretory product. Only trace amounts of 6-hydroxybenzardine and 8-hydroxybenzardine were detected. No conjugation products were found in rats, rabbits, and mice. 6-Hydroxybenzardine and 8-hydroxybenzardine are the major plant metabolites of bentazon. Since humans, livestock, or pets may consume the treated plant, they are theoretically exposed to these two compounds. Although both metabolites have been shown to be produced in mammals, thus qualifying them for toxicological testing of the parent compound, dedicated toxicological studies were conducted. The results showed that the 8-hydroxy and 6-hydroxybenzardine metabolites had comparable toxicity after oral administration, both lower than the parent compound. Furthermore, neither metabolite was detected as inducing bacterial point mutations in the Ames assay. Since the transfer of hydroxyl groups in the bentazon ring system is unlikely to significantly alter its toxicity, 8-hydroxybenzardine was chosen as a reference for further investigation. To this end, subchronic feeding studies, multiple mutagenicity studies, and prenatal developmental studies were conducted on 8-hydroxybenzardine. These studies indicate that these metabolites are not mutagenic or teratogenic, and their toxicity is lower than that of the parent substance. In studies on soybean [Glycine max (Leguminatae) Merr.] and common bean (Phaseolus vulgaris Leguminatae), four unidentified conjugates were observed. Bentazon, after absorption via leaves or roots, is rapidly metabolized in soybean, undergoing hydroxylation at positions 6 and 8. These hydroxylated products are conjugates. Analysis of soybean field samples showed that hydroxylation of bentazon occurs in the early growth stages. Although there were no significant differences in the absorption and translocation of bentazon between resistant and susceptible rice (C. serotinus), significant differences existed in metabolism. In rice, 80% of absorbed bentazon was metabolized within 24 hours and converted to a major water-soluble metabolite within 7 days, with a conversion rate of 85%. In late-flowering lamb's quarter (C. serotinus), only 25-50% of bentazon was metabolized within 7 days. Similar results were obtained in other resistant and susceptible plant species, indicating that the ability to metabolize this compound is the main mechanism of its selectivity. The major metabolite in rice was identified by GC-MS, NMR, and IR as 6-(benzalofop-P-O-β-glucopyranoside. Other studies have shown that soybeans produce roughly equal amounts of 6-hydroxybenzalofop-P-O and 8-hydroxybenzalofop-P-O, while wheat, rice, peanuts, Senecio, and Chenopodium species predominate in 6-hydroxybenzalofop-P-O. For more complete data on the metabolism/metabolites of bentazon (a total of 8 metabolites), please visit the HSDB record page.

Toxicity Summary
Identification and Uses: Bentasol is a white crystalline solid. It has been used as a herbicide. Human Studies: Bentasol is irritating to the eyes and mucous membranes. A 50-year-old man was hospitalized after spraying corn with a bentasol solution, experiencing symptoms including sweating, fever, nausea, watery and bloody vomiting, and hematochezia. He received symptomatic treatment, including extracorporeal hemodialysis, but ultimately developed multiple organ failure (acute respiratory failure, acute liver failure, coagulation disorder, acute kidney failure, metabolic acidosis, and gastrointestinal bleeding) and died 11.35 hours after admission. In another case, intentional ingestion of 130 grams of bentasol resulted in vomiting, fever, sweating, tubular muscle rigidity, sinus tachycardia, drowsiness, leukocytosis, rhabdomyolysis, and liver and kidney damage. Animal Studies: Bentasol is non-irritating to the skin but has moderate eye irritation in rabbits. It is sensitizing to the skin in guinea pigs. In a chronic toxicity study, rats (50 males and 50 females per group) were fed bentazon via diet at doses of 0, 5, 17, and 76 mg/kg body weight/day for two consecutive years. Statistical analysis of tumor incidence revealed no significant differences between groups. Bendasone was not teratogenic in rabbits or rats. In rat developmental studies, a daily dose of 250 mg/kg body weight resulted in increased post-implantation embryo loss, skeletal variations (incomplete or absent ossification of phalangeal nuclei, sternum, and cervical vertebrae), and reduced fetal weight surviving to day 21. No signs of neurotoxicity were observed in rats supplemented with bentazon via diet at dose levels of 0, 300, 1000, and 3500 ppm. In vitro genetic toxicity studies included bacterial reverse mutation assays in Salmonella typhimurium and Escherichia coli, DNA damage and repair studies in Escherichia coli and Saccharomyces cerevisiae, and chromosomal aberration and positive mutation assays in CHO cells. In vivo studies included chromosome analysis in mice and rats, unplanned DNA synthesis assays in mice, and mutation assays in mouse and rat germ cells. Bentazon showed no toxicity in all of these studies. Ecotoxicity studies: Bentazon had effects on zebrafish embryos and their associated bacterial communities. It was non-toxic to bees.

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Toxicity Data
LC50 (rat) = 5,100 mg/m³/4hInteractions
The effects of various cytochrome P450 monooxygenase inhibitors on the absorption and metabolism of the herbicide bentazon were studied using Mexican black sweet corn cell suspension cultures. Bentazon was rapidly absorbed by corn cells and metabolized to glycosylated 6-hydroxybenzon via aryl hydroxylation and glycosylation. The accumulation of bentazon in black corn Mexican sweet corn cells was approximately 20 times that in external media. When black corn Mexican sweet corn cells were cultured in an external medium containing 25 μM bentazon, the formation of glycosylated conjugates (approximately 2 nmol/min/g fresh weight) was rate-limited by aryl hydroxylation. Plant growth inhibitor tetracycline, mechanism-based cytochrome P450 inhibitor phenylhydrazine, and insecticide synergist piperonyl butyl ether all inhibited the metabolism of bentazon, with I50 values of approximately 0.1 μM, 1.0 μM, and 1.0 μM, respectively. Other mechanism-based cytochrome P450 inhibitors, such as 3-(2,4-dichlorophenoxy)-1-propyne and aminobenzotriazole, also inhibited bentazon metabolism, but with poorer effects. The results obtained using the selected inhibitors are consistent with the hypothesis that the aryl hydroxylation of bentazon is catalyzed by cytochrome P450 monooxygenase.

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Non-human toxicity values
Rats oral LD50 850-2470 mg/kg body weight / including free acid and sodium salt forms; data from tables/
Guinea pig oral LD50 1100 mg/kg body weight / free acid and sodium salt forms; data from tables/
Rabbit oral LD50 1139 mg/kg body weight / data from tables/
Rats dermal LD50 >5000 mg/kg body weight / acid form; data from tables/
For more complete non-human toxicity values for bentazon (26 in total), please visit the HSDB records page.

[1]. Herbicide Applications Increase Greenhouse Gas Emissions of Alfalfa Pasture in the Inland Arid Region of Northwest China. PeerJ. 2020 May 25;8:e9231.

Bentazon is a benzothiadiazine compound with the chemical name 1H-2,1,3-benzothiadiazine-4(3H)-one-2,2-dioxide, substituted with an isopropyl group at the 3-position. It is an environmental pollutant, exogenous substance, and herbicide. Bentazon is a herbicide produced by BASF Chemical Company. It belongs to the thiadiazine class of compounds. Sodium bentazon is commercially available and is light brown. The U.S. Environmental Protection Agency (EPA) classifies bentazon as a Group E chemical because, based on animal studies, it is considered non-carcinogenic to humans. However, no studies or experiments have yet determined the toxicity and/or carcinogenicity of bentazon in humans. Mechanism of Action: Inhibits photosynthesis in photosystem II.

C10H12N2O3S

240.28

240.056

25057-89-0

Bentazone-13C10,15N;Bentazone-d7;131842-77-8

2328

Colorless crystals; tech. is an ochre-yellow solid [
White, crystalline powder

1.3±0.1 g/cm3

395.7±25.0 °C at 760 mmHg

137-139°C

193.1±23.2 °C

0.0±0.9 mmHg at 25°C

1.583

2.8

1

4

1

16

385

0

CC(C)N1C(=O)C2=CC=CC=C2NS1(=O)=O

ZOMSMJKLGFBRBS-UHFFFAOYSA-N

InChI=1S/C10H12N2O3S/c1-7(2)12-10(13)8-5-3-4-6-9(8)11-16(12,14)15/h3-7,11H,1-2H3

2,2-dioxo-3-propan-2-yl-1H-2λ6,1,3-benzothiadiazin-4-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.)