Absorption, Distribution and Excretion
Two female goats weighing 43 kg (#1) and 34 kg (#2) (1.4 and 1.8 mg/kg bodyweight respectively), were dosed daily for 3 consecutive days in feed rations treated with (pyrimidine2-(14)C)nicosulfuron, sp. act., 62.2 uCi/mg, radiochemical purity, >95%, isotopic purity, 97%, and (pyridine-2-(14)C)nicosulfuron, sp. act., 62.9 uCi/mg, radiochemical purity, >95%, isotopic purity, >99%, respectively. Dosing capsules were prepared with the (14)C-labeled materials, 13C-enriched isomers (C2 position of each respective ring), and nonradioactive nicosulfuron. The capsules were analyzed prior to dosing by LSC for total (14)C-activity and by HPLC for chemical analysis. These capsules were imbedded in a larger gelatin capsule containing 6 g of goat chow. Goat #1 was housed for a 9-day acclimation period, while goat #2 was kept for 11 days. Both goats showed good health and milk production before and during dosing. The dosage represents a daily feeding level of approximately 60 ppm based on the average feed and hay consumption of 1 kg/day. Samples of milk, bile, urine, and feces were collected daily and analyzed by combustion/liquid scintillation counting. A control goat was not used in the study. Milk, bile, urine, and feces were collected at least one day prior to dosing for use as control samples. ... The administered 14C-dosage was excreted in the urine at 46% and 17%, and in the feces at 62% and 32%, respectively for the pyridinyl- and pyrimidinyl-labeled nicosulfuron. Uptake of residues was low for all tissues and organs for either label. The highest level, 0.1 ppm (0.04% of total dose) was in the liver from the goat treated with the pyridinyl label. All other tissues had total readioactive residue (TRR) of approximately 0.07 ppm or less (nicosulfuron equivalents). Radioactivity in the collected bile comprised 0.1% and 0.7% of the total dose, respectively for the pyridinyl- and pyrimidinyl labeled nicosulfuron. ...
The ... /absorption and elimination/ of /nicosulfuron/ (2-(4,6-dimethoxy-2-pyrimidinyl) aminocarbonylaminosulfonyl-N,N-dimethyl-3-pyridinecarboxamide) was studied in male and female Sprague-Dawley Crl:CDBR rats. Pyridine-2-(14)C nicosulfuron was administered orally at 10 mg/kg or 1000 mg/kg, at 10 mg/kg following oral administration of unlabeled nicosulfuron at 10 mg/kg/day for 14 days, and intravenously at 10 mg/kg. Pyrimidine-2-(14)C labeled nicosulfuron was also administered orally at 1000 mg/kg. Total recovery of administered radioactivity 4 days postdosing accounted for 98-109% of the dose. Most of the radioactivity was excreted unchanged within 24 hours post dosing. With oral dosing, there were no apparent differences between sexes or dose groups, although a slightly greater percentage of the administered radioactivity was detected in feces of animals receiving the high dose than in animals receiving the low dose. Following oral dosing, elimination in the feces accounted for 80 to 95% of the dose, and elimination in the urine accounted for 9 to 20%. Elimination of (14)C-CO2 was negligible (<0.01 of the administered dose). ... Following intravenous administration, approximately 76 to 80% of the dose was eliminated in the urine and 27 to 30% in the feces. Residues in tissues accounted for 0.05 to 0.5% of the dose. The major excretion product in urine and feces was unchanged parent compound. In addition, pyridinesulfonamide (N,N-dimethyl-2-sulfonamide pyridine-3-carboxamide) was detected in the urine and accounted for 1.1 to 5.7% of the dose. Pyridine acid sulfonamide (2-sulfonamidepyridine-3-carboxylic acid) was tentatively identified as a minor metabolite in the feces of orally dosed rats and urine of intravenously dosed rats. ...

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Metabolism / Metabolites
Two female goats weighing 43 kg (#1) and 34 kg (#2) (1.4 and 1.8 mg/kg bodyweight respectively), were dosed daily for 3 consecutive days in feed rations treated with (pyrimidine2-(14)C)nicosulfuron, sp. act., 62.2 uCi/mg, radiochemical purity, >95%, isotopic purity, 97%, and (pyridine-2-(14)C)nicosulfuron, sp. act., 62.9 uCi/mg, radiochemical purity, >95%, isotopic purity, >99%, respectively. Dosing capsules were prepared with the (14)C-labeled materials, 13C-enriched isomers (C2 position of each respective ring), and nonradioactive nicosulfuron. The capsules were analyzed prior to dosing by LSC for total (14)C-activity and by HPLC for chemical analysis. These capsules were imbedded in a larger gelatin capsule containing 6 g of goat chow. Goat #1 was housed for a 9-day acclimation period, while goat #2 was kept for 11 days. Both goats showed good health and milk production before and during dosing. The dosage represents a daily feeding level of approximately 60 ppm based on the average feed and hay consumption of 1 kg/day. Samples of milk, bile, urine, and feces were collected daily and analyzed by combustion/liquid scintillation counting. A control goat was not used in the study. Milk, bile, urine, and feces were collected at least one day prior to dosing for use as control samples. ... The proposed metabolic pathway for nicosulfuron in the goat showed primarily three mechanisms: 1) hydrolysis of the sulfonylurea bridge to yield pyridine sulfonamide and pyrimidine amine (both of which undergo additional metabolism); 2) N-demethylation and subsequent loss of sulfur dioxide leading to the cyclized compound N2; and 3) oxidation and conjugation at the 5-position of the pyrimidine ring.
The metabolism of /nicosulfuron/ (2-(4,6-dimethoxy-2-pyrimidinyl) aminocarbonylaminosulfonyl-N,N-dimethyl-3-pyridinecarboxamide (Accent)) was studied in male and female Sprague-Dawley Crl:CDBR rats. Pyridine-2-(14)C Accent was administered orally at 10 mg/kg or 1000 mg/kg, at 10 mg/kg following oral administration of unlabeled Accent at 10 mg/kg/day for 14 days, and intravenously at 10 mg/kg. Pyrimidine-2-(14)C labeled Accent was also administered orally at 1000 mg/kg. ... Metabolites; / pyridinesulfonamide (N,N-dimethyl-2-sulfonamide pyridine-3-carboxamide) and Pyridine acid sulfonamide (2-sulfonamidepyridine-3-carboxylic acid)/ represent hydrolytic cleavage/oxidation of the parent molecule.

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Biological Half-Life
The ... /absorption and elimination/ of /nicosulfuron/ (2-(4,6-dimethoxy-2-pyrimidinyl) aminocarbonylaminosulfonyl-N,N-dimethyl-3-pyridinecarboxamide) was studied in male and female Sprague-Dawley Crl:CDBR rats. Pyridine-2-(14)C nicosulfuron was administered orally at 10 mg/kg or 1000 mg/kg, at 10 mg/kg following oral administration of unlabeled nicosulfuron at 10 mg/kg/day for 14 days, and intravenously at 10 mg/kg. Pyrimidine-2-(14)C labeled nicosulfuron was also administered orally at 1000 mg/kg. ... The average total cumulative excretion indicated half-lives between 12 and 24 hours.

Non-Human Toxicity Values
LC50 Rat inhalation 5.47 mg/L/4 hr
LD50 Rat dermal >2000 mg/kg
LD50 Mouse oral >5000 mg/kg
LD50 Rat oral >5000 mg/kg

[1]. Nicosulfuron Degradation by an Ascomycete Fungus Isolated From Submerged Alnus Leaf Litter. Front Microbiol. 2018 Dec 19;9:3167.

[2]. Effects of nicosulfuron on plant growth and sugar metabolism in sweet maize (Zea mays L.). PLoS One. 2022 Oct 21;17(10):e0276606.

[3]. Current insights into the microbial degradation of nicosulfuron: Strains, metabolic pathways, and molecular mechanisms. Chemosphere. 2023 Jun;326:138390.

[4]. Adaptation responses in C4 photosynthesis of sweet maize (Zea mays L.) exposed to nicosulfuron. Ecotoxicol Environ Saf. 2021 May;214:112096.

Nicosulfuron is a N-sulfonylurea that is 2-(carbamoylsulfamoyl)-N,N-dimethylpyridine-3-carboxamide substituted by a 4,6-dimethoxypyrimidin-2-yl group at the amino nitrogen. It has a role as an environmental contaminant, a xenobiotic and a herbicide. It is a member of pyridines, a N-sulfonylurea and a member of pyrimidines.

C15H18N6O6S

410.41

410.1

111991-09-4

Nicosulfuron-d6;1189419-41-7

73281

White to off-white solid powder

1.5±0.1 g/cm3

719.1±70.0 °C at 760 mmHg

141-144°C

388.7±35.7 °C

0.0±2.4 mmHg at 25°C

1.640

-2.09

2

9

6

28

642

0

RTCOGUMHFFWOJV-UHFFFAOYSA-N

InChI=1S/C15H18N6O6S/c1-21(2)13(22)9-6-5-7-16-12(9)28(24,25)20-15(23)19-14-17-10(26-3)8-11(18-14)27-4/h5-8H,1-4H3,(H2,17,18,19,20,23)

2-[(4,6-dimethoxypyrimidin-2-yl)carbamoylsulfamoyl]-N,N-dimethylpyridine-3-carboxamide

Milagro; Accent; Nicosulfuron

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~33.33 mg/mL (~81.21 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.09 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 25.0 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: ≥ 2.5 mg/mL (6.09 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 25.0 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.)