Absorption, Distribution and Excretion
Two female goats, weighing 43 kg (#1) and 34 kg (#2) respectively (weights of 1.4 and 1.8 mg/kg), were fed daily for three consecutive days diets supplemented with (pyrimidine-2-(14)C) nicosulfuron (specific activity 62.2 uCi/mg, radiochemical purity >95%, isotopic purity 97%) and (pyridine-2-(14)C) nicosulfuron (specific activity 62.9 uCi/mg, radiochemical purity >95%, isotopic purity >99%). The administration capsules were made from (14)C-labeled material, 13C enriched isomers (C2 position of each ring), and non-radioactive nicosulfuron. Prior to administration, the total 14C activity of the capsules was analyzed using liquid scintillation counting (LSC), and the chemical composition was analyzed using high-performance liquid chromatography (HPLC). These capsules were encapsulated in a larger gelatin capsule containing 6 grams of goat feed. The acclimatization period for goat #1 was 9 days, and for goat #2, it was 11 days. Both goats exhibited good health and milk production before and after administration. Based on an average daily consumption of 1 kg of feed and hay, the administered dose was equivalent to approximately 60 ppm of the daily feed intake. Milk, bile, urine, and fecal samples were collected daily and analyzed using a combustion/liquid scintillation counting method. No control goats were included in this study. Control samples were collected at least one day prior to administration. 46% and 17% of the 14C dose of pyridyl and pyrimidyl-labeled nicotinamide were excreted in urine, and 62% and 32% in feces, respectively. Residues of both nicotinamide labels were low in all tissues and organs. The highest residue level was found in the liver of goats treated with pyridyl-labeled nicotinamide, at 0.1 ppm (0.04% of the total dose). The total residual radioactivity (TRR) in all other tissues was approximately 0.07 ppm or less (in nicotinamide equivalents). The radioactivity of pyridyl and pyrimidyl-labeled nicotinamide in the collected bile accounted for 0.1% and 0.7% of the total dose, respectively. This study investigated the absorption and elimination of nicotinamide sulfonylurea (2-(4,6-dimethoxy-2-pyrimidinyl)aminocarbonylaminosulfonyl-N,N-dimethyl-3-pyridinecarboxamide) in male and female Sprague-Dawley Crl:CDBR rats. The following administration methods were used: oral administration of 10 mg/kg or 1000 mg/kg of pyridine-2-(14)C-labeled nicotinamide sulfonylurea; oral administration of 10 mg/kg of unlabeled nicotinamide sulfonylurea (10 mg/kg/day for 14 consecutive days); and intravenous administration of 10 mg/kg of nicotinamide sulfonylurea... Within 24 hours after administration, most of the radioactive material was eliminated unchanged. Following oral administration, no significant differences were observed between sexes or dose groups, but the percentage of radioactive material detected in feces was slightly higher in the high-dose group than in the low-dose group. After oral administration, 80% to 95% of the dose was excreted in feces and 9% to 20% in urine. The excretion of C-CO2 was negligible (<0.01g of the dose). …After intravenous administration, approximately 76% to 80% of the dose was excreted in urine and 27% to 30% in feces. Tissue residues were 0.05% to 0.5% of the dose. The main excretion products in urine and feces were the unchanged parent compound. Furthermore, pyridine sulfonamide (N,N-dimethyl-2-sulfonamide-pyridine-3-carboxamide) was detected in urine at levels ranging from 1.1% to 5.7% of the dose. Pyridine sulfonamide (2-sulfonamide pyridine-3-carboxylic acid) was preliminarily identified as a small metabolite in the feces of rats administered orally and in the urine of rats administered intravenously. …

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Metabolites/Metabolites
Two female goats weighing 43 kg (#1) and 34 kg (#2), respectively (weights of 1.4 and 1.8 mg/kg, respectively), were fed a diet supplemented with (pyrimidine-2-(14)C) nicosulfuron for three consecutive days. The activity was 62.2 uCi/mg, radiochemical purity >95%, isotopic purity 97%, and (pyrimidine-2-(14)C) nicosulfuron (specific activity 62.9 uCi/mg, radiochemical purity >95%, isotopic purity >99%). The administration capsules were prepared from (14)C labeled material, 13C enriched isomers (C2 position of each ring), and non-radioactive nicosulfuron. Prior to administration, total (14)C activity of the capsules was analyzed using liquid scintillation counting (LSC), and chemical composition was analyzed using high-performance liquid chromatography (HPLC). These capsules were embedded in larger gelatin capsules containing 6 g of goat feed. Adaptation time was 9 days for goat #1 and 11 days for goat #2. Both goats exhibited good health and milk production before and after administration. The dosage was equivalent to approximately 60 ppm of daily feed intake, calculated based on an average daily feed and hay consumption of 1 kg. Milk, bile, urine, and fecal samples were collected daily and analyzed using combustion/liquid scintillation counting. No control goats were included in this study. Milk, bile, urine, and fecal samples were collected at least one day prior to administration as control samples. ...The proposed metabolic pathway of nicosulfuron in goats mainly involves three mechanisms: 1) hydrolysis of sulfonylurea bridges to generate pyridinesulfonamide and pyrimidineamine (both of which require further metabolism); 2) N-demethylation followed by loss of sulfur dioxide to generate the cyclic compound N2; 3) oxidation and conjugation at the 5-position of the pyrimidine ring.
This study investigated the metabolism of nicosulfuron (2-(4,6-dimethoxy-2-pyrimidinyl)aminocarbonylaminosulfonyl-N,N-dimethyl-3-pyridinecarboxamide (Accent)) in male and female Sprague-Dawley Crl:CDBR rats. Accent was administered orally at doses of 10 mg/kg or 1000 mg/kg, or, after 14 consecutive days of oral administration of unlabeled Accent at a dose of 10 mg/kg/day, was administered intravenously at a dose of 10 mg/kg. In addition, pyrimidine-2-(14)C-labeled Accent was administered orally at a dose of 1000 mg/kg. ... Metabolites; /pyridinesulfonamide (N,N-dimethyl-2-sulfonamide-pyridine-3-carboxamide) and pyridinesulfonamide (2-sulfonamide-pyridine-3-carboxylic acid) / represent the 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) were investigated in male and female Sprague-Dawley Crl:CDBR rats. Pyridine-2-(14)C-labeled nicosulfuron was administered orally at doses of 10 mg/kg or 1000 mg/kg, or intravenously at doses of 10 mg/kg following 14 consecutive days of oral administration of unlabeled nicosulfuron. Pyrimidine-2-(14)C-labeled nicosulfuron was also administered orally at a dose of 1000 mg/kg. …The mean total cumulative excretion indicated a half-life between 12 and 24 hours.

Non-Human Toxicity Values
Rat inhalation LC50: 5.47 mg/L/4 hours
Rat dermal LD50: >2000 mg/kg
Mouse oral LD50: >5000 mg/kg
Rat oral LD50: >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 an N-sulfonylurea compound with the chemical name 2-(carbamoylsulfonyl)-N,N-dimethylpyridine-3-carboxamide, where the amino nitrogen atom is substituted with a 4,6-dimethoxypyrimidin-2-yl group. It is an environmental pollutant, exogenous substance, and herbicide. It belongs to the pyridine, N-sulfonylurea, and pyrimidine classes of compounds.

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.)