Absorption, Distribution and Excretion
Toxicokinetic studies performed on mice, rats and rabbits indicate that bentazone is rapidly and almost completely absorbed via the oral route (> 99%), and maximum blood concentrations of radioactivity are achieved in approximately 15 minutes at low doses (4 mg/kg bw) and by 1 hour at high doses (200 mg/kg bw). Administration of bentazone either as the sodium salt or as the free acid did not result in any significant differences in absorption. There was no evidence of penetration into the central nervous system or spinal cord, and elimination from other tissues was rapid, with no indication of bioaccumulation. Elimination was almost exclusively via the urine (approximately 91% within 24 hours); 5 days after dosing, less than 2% was found in feces and less than 0.02% in expired air. Biliary excretion of radioactivity was minimal. No significant differences were found in absorption and elimination among the different species investigated (rat, rabbit, mouse).
The dermal penetration of [14C]bentazone sodium salt (batch no. 210-2201, radiochemical purity 97.3%) through human skin was assessed by a single topical application of about 4933, 49.3 or 8.22 ug/sq cm of active ingredient formulated in BAS 351 32 H to split thickness skin membranes mounted on Franz-type diffusion cells. The doses represent the formulation concentrate or two representative spray dilutions (1:100 and 1:600) for field use, respectively. The study was performed using five diffusion cells per dose. ... It can be concluded that in vitro dermal penetration of bentazone formulated as an aqueous soluble (liquid) concentrate formulation of bentazone sodium through human skin is appropriately calculated as per cent absorbed dose. Considering the amount of radiolabeled substance associated with the skin (remaining skin and tape strips 3-6) after washing as absorbable and combining this with the absorbed amount detected in the receptor, the extent of dermal penetration through human epidermis is about 0.06% for the concentrate, 1.31% for the 1:100 spray strength dilution and 1.23% for the 1:600 dilution. /Bentazone sodium salt/
A case of fatal suicidal bentazone poisoning was presented along with a description of the different analytical methods involved. A 56-year-old farmer was examined by the family doctor 1 hour after voluntarily ingesting 500 mL of FIGHTER (about 250 g bentazone). He presented a Glasgow score of 15, polypnea, diarrhea and vomiting. During transport by ambulance to the hospital, he tossed, sweated and suddenly presented breathing difficulty followed by heart failure. The patient died within 2 hours post-ingestion. Blood and urine samples were taken just before death. Bentazone plasma and urine levels were 1500 and 1000 mg/L, respectively.
A 59-year-old woman who intentionally ingested 100-200 mL Basagran (about 50-100 g bentazone) was taken to the hospital with cardiac arrest 2 days after she had consumed the herbicide. During this period, she suffered vomiting, urination and diarrhoea, and she was drowsy with a muddled speech. Biological samples obtained at the autopsy were analysed, and the presence of bentazone, alcohol and an active metabolite of citalopram was detected. Blood concentrations of bentazone, alcohol and desmethyl-citalopram were 625 mg/kg, 0.62 g/L and 0.03 mg/kg, respectively.

---

Metabolism / Metabolites
The metabolism of bentazone was investigated in a number of toxicokinetic studies following oral (rat and rabbit) or intravenous administration (mouse) ... . Bentazone was only poorly metabolized, with the parent compound being the predominant excretion product. Only small amounts of 6-hydroxybentazone and 8-hydroxybentazone could be detected. In rats, rabbits and mice, no conjugated products were found.
6-Hydroxybentazone and 8-hydroxybentazone are major plant metabolites of bentazone. Because crops of treated plants can be consumed by humans, farm animals or pets, an exposure to both of these compounds might be expected in principle. Although both metabolites have been demonstrated to be formed in mammals and therefore can be regarded as included in toxicological testing of the parent compound, specific toxicological studies were performed. It has been shown that the 8-hydroxy and 6-hydroxy metabolites of bentazone are of comparable toxicity by the oral route of administration and are both less toxic than the parent compound. Additionally, both metabolites were negative in the Ames assay for the potential to induce point mutations in bacteria. As it is unlikely that a hydroxy group shift in the bentazone ring system dramatically changes the toxicity, it was decided to perform further investigations on 8-hydroxybentazone as a reference substance. Therefore, 8-hydroxybentazone was investigated in a subchronic feeding study, in several mutagenicity studies and in a prenatal developmental study. These investigations revealed that the metabolites have no mutagenic or teratogenic potential and are less toxic than the parent substance.
In studies with soybeans [Glycine max (Leguminatae) Merr.] and navy beans (Phaseolus vulgaris Leguminatae), four unidentified conjugates were observed. After foliar or root absorption, bentazon was rapidly metabolized by soybeans with hydroxylation at the 6 and 8 position. These were conjugated. Analysis of soybean field samples showed hydroxylation of bentazon in early growth stages.
Although absorption and translocation of bentazon was not markedly different in resistant rice and susceptible C. serotinus, metabolism differed markedly. In rice, there was 80% metabolism of absorbed bentazon within 24 hr and 85% conversion to a major water soluble metabolite within 7 days. In C. serotinus, there was only 25-50% metabolism of bentazon in 7 days. Similar results were obtained with other resistant and susceptible plant species indicating that ability to metabolize this compound is the primary mechanism of selectivity. The primary metabolite in rice was identified by GC-MS, NMR and IR as 6-(bentazon)-O-beta-glucopyranoside. Other studies showed that the 6- and 8-hydroxybentazon were formed in about equal amounts in soybeans and that the 6-hydroxy analog predominates in wheat, rice, peanuts, Senecio sp., and Chenopodium sp.
For more Metabolism/Metabolites (Complete) data for Bentazon (8 total), please visit the HSDB record page.

Toxicity Summary
IDENTIFICATION AND USE: Bentazone is a white, crystalline solid. It was formerly used as an herbicide. HUMAN STUDIES: Bentazone is irritating to eyes and mucous membranes. A 50-year-old male who had sprayed corn with a solution of bentazone was admitted to the hospital with sweating, fever, nausea, vomiting of aqueous and hemorrhagic content, and bloody, watery stools. He was treated according to the symptoms including extracorporeal hemodialysis, but eventually suffered from multiorgan failure (acute respiratory failure, acute liver failure, coagulopathy, acute renal failure, metabolic acidosis, and gastrointestinal bleeding) and died 11.35 hr after admittance. In another case, intentional poisoning with 130 g of bentazone resulted in vomiting, fever, sweating, pipe-like muscle rigidity, sinus tachycardia, drowsiness, leukocytosis, rhabdomyolysis and hepatorenal damage. ANIMAL STUDIES: Bentazone is not a skin irritant but was a moderate eye irritant in rabbits. It is a skin sensitizer in guinea-pigs. In a chronic toxicity study, bentazone was administered to rats (50 of each sex per group) via a diet at doses 0, 5, 17 and 76 mg/kg bw per day for 2 years. Statistical analysis of tumor incidence did not reveal any significance among the groups tested. Bentazone was not teratogenic in rabbits or rats. In rat developmental studies, it increased post-implantation loss, skeletal variations (incomplete or absent ossification in the phalangeal nuclei of the extremities, sternebrae and cervical vertebrae) and reduced body weights of fetuses surviving to day 21 at 250 mg/kg bw per day. Dietary administration of bentazone to rats at dose levels of 0, 300, 1000 and 3500 ppm did not result in any indication of neurotoxicity. In vitro genotoxicity studies included bacterial reverse mutation assays on Salmonella typhimurium and Escherichia coli, DNA damage and repair studies on E. coli and Saccharomyces cerevisiae, and chromosomal aberration and forward mutation assays in CHO cells. In vivo studies included chromosome analyses in mice and rats, unscheduled DNA synthesis tests in mice, and mutation assays in germ cells for mice and rats. Bentazone gave negative results in all of these studies. ECOTOXICITY STUDIES: Bentazone affected zebrafish embryos and associated bacterial communities. It was nontoxic to bees.

---

Toxicity Data
LC50 (rat) = 5,100 mg/m3/4h

---

Interactions
Maize black Mexican sweet cell suspension cultures were used to study the effects of various cytochrome p450 monooxygenase inhibitors on the uptake and metabolism of the herbicide bentazon. Maize cells rapidly absorbed bentazon and metabolized it via aryl hydroxylation and glycosylation to a glycosyl conjugate of 6-hydroxybentazon. Maize black Mexican sweet cells accumulated bentazon to levels approximately 20 fold greater than those in the external medium. When maize black Mexican sweet cells were incubated in an external medium containing 25 uM bentazon, the formation of the glycosyl conjugate (ca 2 nmol/min/g fresh wt) was rate limited by aryl hydroxylation. Tetcyclacis, a plant growth retardant, phenylhydrazine, a mechanism based cytochrome p450 inhibitor, and piperonyl butoxide, an insecticide synergist, inhibited bentazon metabolism with I50 values of approximately 0.1, 1.0, and 1.0 uM, respectively. Other mechanism based cytochrome p450 inhibitors, 3(2,4-dichlorophenoxy)-1-propyne and aminobenzotriazole, also inhibited bentazon metabolism but were less effective. The results obtained with selected inhibitors are consistent with the hypothesis that aryl hydroxylation of bentazon is catalyzed by a cytochrome p450 monooxygenase.

---

Non-Human Toxicity Values
LD50 Rat oral 850-2470 mg/kg bw /Includes free acid and sodium salt forms; From table/
LD50 Guinea pig oral 1100 mg/kg bw /Free acid and sodium salt forms; From table/
LD50 Rabbit oral 1139 mg/kg bw /From table/
LD50 Rat dermal >5000 mg/kg bw /Acid form; From table/
For more Non-Human Toxicity Values (Complete) data for Bentazon (26 total), please visit the HSDB record 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.

Bentazone is a benzothiadiazine that is 1H-2,1,3-benzothiadiazin-4(3H)-one 2,2-dioxide substituted by an isopropyl group at position 3. It has a role as an environmental contaminant, a xenobiotic and a herbicide.
Bentazon is a chemical manufactured by BASF Chemicals for use in herbicides. It is categorized under the thiadiazine group of chemicals. Sodium bentazon is available commercially and appears slightly brown in colour. Bentazon has been classified by the EPA as a Group E chemical, because it is believed to be non-carcinogenic to humans (as based on testing conducted on animals). However, there are no studies or experiments that can determine toxic and/or carcinogenic effects of bentazon on humans.

---

Mechanism of Action
Inhibition of photosynthesis at 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.

---

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).

View More

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)

---

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).

View More

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

---

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.

---

 (Please use freshly prepared in vivo formulations for optimal results.)