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: Absorption occurs through both the foliage and roots.
Rapidly excreted primarily in the urine following iv admin /to rats/, and in the urine and feces following oral admin, mainly as unchanged parent.
Forty-four Sprague Dawley rats (5/sex/group) were dosed with (14)C-/imazamox/ by a single intravenous (iv) dose at 10 mg/kg or a single oral gavage dose according to the following regiments: (1) 10 mg/kg body weight; (2) 14-day preconditioning with 10 mg/kg non-radiolabelled /imazamox/, followed by 10 mg/kg (14)C-/imazamox/; or (3) 1000 mg/kg body weight. The elimination patterns indicated that the radioactive residue were rapidly cleared from the body (ca. 95%) excreted in urine and recovered within 12 hours after dosing for all dose groups. Approximately, 74-75% of the radioactivity was absorbed via oral administration at 10 mg/kg dose and 74.4-74.5% excreted in urine and 18.7- 24.0% in feces. Much higher proportion of the dose was excreted in feces following oral dose (18.7- 24.0%) compared to iv injection (1.9-2.7%), most likely due to incomplete absorption. Three components accounted for ca. 99% of the total urinary radioactivity (98.2%, parent; 0.6%, 5- hydroxymethyl-nicotinic acid metabolite; and 0.4%, 5-carboxy-nicotinic acid metabolite) and ca. 89% of the extractable radioactivity in the feces (76.4%, parent; 9.6%, 5-hydroxymethyl-nicotinic acid metabolite; and 2.5%, 5-carboxy-nicotinic acid metabolite). The radioactive residues in the tissues were low (< 0.007%), and no (14)C-residues were detected in the expired air.
In rats, imazamox was rapidly absorbed, and the oral absorption was approximately 75% of the administered dose. Urine was the major route of excretion (>74%).

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Metabolism / Metabolites
Imazamox is a racemic mixture. No information on chiral conversion in the mammalian metabolism or toxicity of specific enantiomer is available. However, information available in the fate and behaviour and residues section indicated that chiral conversion does not occur and exposure would be only to the racemic mixture.
Forty-four Sprague Dawley rats (5/sex/group) were dosed with (14)C-/imazamox/ ...Three components accounted for ca. 99% of the total urinary radioactivity (98.2%, parent; 0.6%, 5- hydroxymethyl-nicotinic acid metabolite; and 0.4%, 5-carboxy-nicotinic acid metabolite) and ca. 89% of the extractable radioactivity in the feces (76.4%, parent; 9.6%, 5-hydroxymethyl-nicotinic acid metabolite; and 2.5%, 5-carboxy-nicotinic acid metabolite). The radioactive residues in the tissues were low (<0.007%), and no (14)C-residues were detected in the expired air.
(14)C-(15)N-labelled/unlabelled imazamox mix was incubated with dog, rabbit, rat, mouse or human liver microsomes in the presence of a nicotinamide adenine dinucleotide phosphate (NADPH)-generating system. With 90% recovered radioactivity and above, only the parent molecule was detected in all test systems by high-performance liquid chromatographic analysis in fresh samples after the incubation. Under the conditions of the study, imazamox was not metabolized by liver microsomes of dogs, rabbits, rats, mice or humans. No unique human metabolite was detected. Under the conditions of the study, the positive control, testosterone, was metabolized by the microsome samples originating from different species.
In rats, imazamox was rapidly absorbed, and the oral absorption was approximately 75% of the administered dose. Urine was the major route of excretion (>74%). Most of the elimination occurred within the first 24 hours after dosing, as unchanged parent compound. Smaller amounts of the test substance were excreted through faeces (>19% in animals receiving 10 mg/kg bw and approximately 10-20% in animals receiving 1000 mg/kg bw). Only trace amounts of tissue residue were detected. Imazamox appears not to be metabolized. Trace levels of imazamox-related compounds detected in the urine and faeces were attributed to the presence of impurities in the dosing solution, not to rat metabolism.

Toxicity Summary
IDENTIFICATION AND USE: Imazamox is off-white powdered solid. It is a herbicide applied post-emergence in soybean. HUMAN STUDIES: In an in vitro study, human embryonic stem cells were treated with imazamox at a concentration of 0, 1, 10 or 100 umol/L, incubation did not induce cytotoxicity. ANIMAL STUDIES: In the acute toxicity studies, the substance has low acute toxicity when administered orally, dermally or by inhalation to rats. It is not a significant skin or eye irritant or a skin sensitizer. Imazamox showed no short-term and long-term toxicity after oral exposure to rats, mice and dogs up to the limit top dose level tested in each study. Based on available genotoxicity studies imazamox is unlikely to be genotoxic. The substance showed no carcinogenic potential in both species. In the multigeneration toxicity study, fertility and overall reproductive performance was not impaired. In developmental toxicity studies maternal toxicity in rats and in rabbits was observed. No developmental toxicity was observed in rats whereas agenesis of the intermediate lobe of lung and cervical hemivertebra was observed in rabbits. ECOTOXICITY STUDIES: Imazamox is practically nontoxic to avian species, finfish, aquatic invertebrates, and honeybees following acute exposure.

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

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Non-Human Toxicity Values
LD50 Rat oral >5000 mg/kg bw
LD50 Rabbit dermal >4000 mg/kg bw

[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 pyridinemonocarboxylic acid that is nicotinic acid which is substituted substituted at position 5 by a methoxymethyl group and at position 2 by a 4,5-dihydro-1H-imidazol-2-yl group, that in turn is substituted by isopropyl, methyl, and oxo groups at positions 4, 4, and 5, respectively. It is a pyridinemonocarboxylic acid, an ether, an imidazolone and a member of imidazolines.
Imazamox is a member of the imidazolinone class of herbicides. It is registered for post-emergence control of broadleaf weeds and grass in alfalfa, edible legumes and soybeans. It is a systemic herbicide that moves throughout the plant tissue and prevents plants from producing an essential enzyme, acetolactate synthase (ALS), which is not found in animals. This enzyme is key for the biosynthesis of branched chain amino acids. Susceptible plants will stop growing soon after treatment, but plant death and decomposition will occur over several 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.)