Methapyr has a half-life of one to three months in soil and is not very harmful to mammals [1]. After seven days of treatment with imazamox (250 μM) in nutrient solution, the plants were harvested. Imazethapyr is six times more abundant in V. sativa than it is in P. vulgaris and mostly accumulates in that plant [3].

Treatment with imazapyr (12-36 mg/kg; i.p.; 24-72 hours; male Sprague-Dawley rats) induces toxic effects on the liver and pancreas of Sprague Dawley rats. At the two highest doses, necrotic and degenerative alterations were found in hepatocytes. Treatment with imazethapyr lowers the size of β-islet cells and induces increases in blood glucose and calcium [4].

Animal/Disease Models: 50 male SD (SD (Sprague-Dawley)) rats (300±10g) [3]
Doses: 12mg/kg, 24mg/kg and 36mg/kg
Route of Administration: intraperitoneal (ip) injection; 24 hrs (hrs (hours)), 48 hrs (hrs (hours)) or 72 hrs (hrs (hours))
Experimental Results: Yes Toxic effects on the liver and pancreas.

Absorption, Distribution and Excretion
Plant Absorption: Absorbed through leaves and roots. After intravenous injection (rat), it is rapidly excreted primarily in urine; after oral administration, it is primarily excreted unchanged in urine and feces. Forty-four Sprague Dawley rats (five males and five females per group) received either a single intravenous (iv) injection of 10 mg/kg of (14)C-/imidazolinone/ or a single gavage administration of (14)C-/imidazolinone/, with the following administration regimens: (1) 10 mg/kg body weight; (2) pretreatment with 10 mg/kg of unlabeled imidazolinone/ for 14 days followed by administration of 10 mg/kg of (14)C-/imidazolinone/; or (3) 1000 mg/kg body weight. The clearance pattern indicated that radioactive residues were rapidly cleared from the body (approximately 95%), primarily excreted in urine, and were recovered within 12 hours of administration in all dose groups. At an oral dose of 10 mg/kg, approximately 74-75% of the radioactivity is absorbed, with 74.4-74.5% excreted in urine and 18.7-24.0% in feces. The proportion of the dose excreted in feces after oral administration (18.7-24.0%) is significantly higher than that after intravenous injection (1.9-2.7%), likely due to incomplete absorption. Approximately 99% of the radioactivity in urine consists of three components (98.2% of the parent compound; 0.6% of 5-hydroxymethylnicotinic acid metabolites; and 0.4% of 5-carboxynicotinic acid metabolites). 89% of the radioactive material can be extracted from feces (76.4% of the parent compound; 9.6% of 5-hydroxymethylnicotinic acid metabolites; and 2.5% of 5-carboxynicotinic acid metabolites). The residual radioactivity in tissues is very low (< 0.007%), and no ¹⁴C residues were detected in exhaled breath.
In rats, imidazolix is rapidly absorbed, with an oral absorption rate of approximately 75% of the administered dose. Urine is the primary route of excretion (>74%).

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Metabolism/Metabolites
Imidolimus is a racemic mixture. Information is currently unavailable regarding chiral conversion or specific enantiomeric toxicity during its metabolism in mammals. However, information available on fate, behavior, and residual components suggests that chiral conversion does not occur, and the exposed subjects are only exposed to the racemic mixture.
Forty-four Sprague Dawley rats (five males and five females per group) received (14)C-/imidazolinone/... components, which accounted for approximately 99% of the total urinary radioactivity (98.2%, maternal; 0.6%, 5-hydroxymethylnicotinic acid metabolite; 0.4%, 5-carboxynicotinic acid metabolite) and approximately 89% of the fecal extractable radioactivity (76.4%, maternal; 9.6%, 5-hydroxymethylnicotinic acid metabolite; 2.5%, 5-carboxynicotinic acid metabolite). The radioactive residue in tissues was extremely low (<0.007%), and no ¹⁴C residues were detected in exhaled breath.
A mixture of ¹⁴C-¹⁵N-labeled/unlabeled imidazolinones was incubated with canine, rabbit, rat, mouse, or human liver microsomes in the presence of a nicotinamide adenine dinucleotide phosphate (NADPH) generating system. With radioactive recovery rates of 90% or higher, fresh samples after incubation were analyzed by high-performance liquid chromatography (HPLC), and only the parent molecule was detected in all test systems. Under the conditions of this study, imidazolinones were not metabolized by canine, rabbit, rat, mouse, or human liver microsomes. No human-specific metabolites were detected. Under the conditions of this study, the positive control testosterone was metabolized by microsomal samples from different species.
In rats, imidazolix is rapidly absorbed, with an oral absorption rate of approximately 75% of the administered dose. Urine is the main route of excretion (>74%). Most of the drug was excreted unchanged within 24 hours after administration. Small amounts of the test substance were excreted in feces (>19% for the 10 mg/kg body weight, approximately 10-20% for the 1000 mg/kg body weight). Only trace amounts of tissue residue were detected. Mizolimus appeared to be unmetabolized. The trace amounts of mizolimus-related compounds detected in urine and feces were attributed to the presence of impurities in the administration solution, rather than to rat metabolism.

Toxicity Summary
Identification and Uses: Imidazolinone is a grayish-white powdery solid. It is a post-emergence herbicide for soybeans. Human Studies: In an in vitro study, treatment of human embryonic stem cells with imidazolinone at concentrations of 0, 1, 10, or 100 μmol/L did not induce cytotoxicity. Animal Studies: In acute toxicity studies, the substance showed low acute toxicity in rats via oral, dermal, or inhalation routes. It is not an obvious skin or eye irritant or skin sensitizer. Oral exposure to imidazolinone did not show short-term or long-term toxicity in rats, mice, and dogs at the highest dose levels tested in each study. Based on existing genotoxicity studies, imidazolinone is unlikely to be genotoxic. The substance did not show carcinogenicity in either animal group. In multigenerational toxicity studies, fertility and overall reproductive performance were not impaired. In developmental toxicity studies, maternal toxicity was observed in rats and rabbits. No developmental toxicity was observed in rats, while pulmonary interlobar dysplasia and cervical hemivertebrae dysplasia were observed in rabbits. Ecotoxicity studies: Following acute exposure, imidazoline is virtually non-toxic to birds, fish, aquatic invertebrates, and bees.

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Toxicity Data
LC50 (Rat)> 6,300 mg/m3

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Non-human Toxicity Values
LD50 (Rats, Oral)> 5000 mg/kg body weight
LD50 (Rabbit, Dermal)> 4000 mg/kg body weight

[1]. Enantioselective Phytotoxicity of Imazamox Against Maize Seedlings. Bull Environ Contam Toxicol. 2016 Feb;96(2):242-7.

[2]. Metabolic responses in root nodules of Phaseolus vulgaris and Vicia sativa exposed to the imazamox herbicide. Pestic Biochem Physiol. 2014 May;111:19-23.

[3]. Imazamox Chemical Fact Sheet. Wisconsin Department of Natural Resources. DNR PUB-WT-974 2012.

[4]. An imazamox-based herbicide causes apoptotic changes in rat liver and pancreas. Toxicol Rep. 2018 Nov 19;6:42-50.

2-(4-Isopropyl-4-methyl-5-oxo-4,5-dihydro-1H-imidazol-2-yl)-5-(methoxymethyl)nicotinic acid is a pyridine monocarboxylic acid compound in which nicotinic acid is substituted at the 5-position with a methoxymethyl group, at the 2-position with a 4,5-dihydro-1H-imidazol-2-yl group, and the 4,5-dihydro-1H-imidazol-2-yl group is further substituted at the 4, 5, and 6-positions with isopropyl, methyl, and oxo groups, respectively. It is a pyridine monocarboxylic acid, ether, and imidazolinone, belonging to the imidazoline herbicide class. Imidazolinone herbicides (Imazamox) are registered for post-emergence control of broadleaf and grass weeds in alfalfa, legumes, and soybean fields. This is a systemic herbicide that penetrates plant tissues and inhibits the production of acetolactate synthase (ALS), an essential enzyme not found in animals. This enzyme is a key enzyme in the biosynthesis of branched-chain amino acids. Sensitive plants will stop growing shortly after treatment, but the process of death and decay will be completed within a few weeks.

C15H19N3O4

305.33

305.137

114311-32-9

Imazamox-13C,d3

86137

White to off-white solid powder

1.3±0.1 g/cm3

166-167°C

1.603

0.25

2

6

5

22

491

0

NUPJIGQFXCQJBK-UHFFFAOYSA-N

InChI=1S/C15H19N3O4/c1-8(2)15(3)14(21)17-12(18-15)11-10(13(19)20)5-9(6-16-11)7-22-4/h5-6,8H,7H2,1-4H3,(H,19,20)(H,17,18,21)

5-(methoxymethyl)-2-(4-methyl-5-oxo-4-propan-2-yl-1H-imidazol-2-yl)pyridine-3-carboxylic acid

AC-299263; AC 299263; Imazamox

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)

DMSO : ~20 mg/mL (~65.50 mM)

Solubility in Formulation 1: ≥ 2 mg/mL (6.55 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2 mg/mL (6.55 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

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Solubility in Formulation 3: ≥ 2 mg/mL (6.55 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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