Absorption, Distribution and Excretion
…Adult male Fischer 344 rats were administered a single oral dose of 0.025 mCi (0.38 mg) of [¹⁴C]melamine. Within 24 hours, 90% of the administered dose was excreted in the urine. Radioactive levels in respiration and feces were extremely low. ¹⁴C concentrations in blood, liver, and plasma showed little difference, indicating that melamine was distributed in body fluids. Radioactivity levels in the kidneys and bladder were significantly higher than in plasma. The highest radioactivity levels were observed in the bladder, likely due to backdiffusion of radioactive material from urine or contamination of bladder tissue by urine. Almost no residual radioactivity was observed in tissues examined 24 hours or longer. The elimination half-life calculated from plasma data was 2.7 hours, which is in good agreement with the urinary excretion half-life of 3.0 hours. The renal clearance of melamine was 2.5 mL/min.
...After oral administration of 250 mg/kg melamine to rats, 50% of the parent compound was excreted in the urine within 6 hours. ...The crystals found in the urine consisted of melamine diphosphate, accounting for approximately 20% of the administered dose. After melamine administration to dogs, 60% to 86.5% of the parent compound was recovered in the urine within 24 hours. ...
A dose of 2.4 g/kg caused diuresis and resulted in the excretion of small crystals of melamine diphosphate in the urine.
After a single oral administration of 0.38 mg (14)C-melamine to adult male Fischer 344/N rats, 90% of the administered dose was excreted in the urine within 24 hours. Radioactivity detected in exhaled breath and feces was negligible; radioactivity was mainly concentrated in the kidneys and bladder. Almost no residual radioactivity was observed in tissues 24 hours or longer. Chromatographic analysis of radioactive substances in plasma or urine showed that melamine is not metabolized in rats. Metabolites/Metabolites: Toxicokinetic studies were conducted in rats with single and repeated oral administration of 14C-labeled cyclopromethazine. Results showed that the active substance was rapidly and almost completely absorbed from the gastrointestinal tract and distributed to all organs and tissues. …Cyclopromethazine is incompletely metabolized, primarily through methylation, hydroxylation, or N-dealkylation. The main component is cyclopromethazine, accounting for 71-72% of the radiolabeled substances; another 7% is attributed to melamine, and 8-11% to hydroxycyclopromethazine and methylcyclopromethazine. …A single oral administration of 0.025 mCi (0.38 mg) of [14C]melamine to adult male Fischer 344 rats. …Cochromatographic analysis of radioactivity in plasma or urine with that in the administered solution showed that melamine is not metabolized in male Fischer 344 rats.
Cryuria is caused by the excretion of melamine monophosphate crystals.
In oral administration studies in rats, melamine was not metabolized and was rapidly excreted in the urine. (L1777)

---

Biological half-life
……A single oral administration of 0.025 mCi (0.38 mg) of [14C]melamine to adult male Fischer 344 rats. ……The elimination half-life calculated from plasma data was 2.7 hours, which is in good agreement with the urinary excretion half-life of 3.0 hours. ……

Toxicity Summary
Substance Identification: Melamine is a monoclinic prismatic crystal, slightly soluble in water and ethanol, and insoluble in ether. Melamine can form synthetic resins with formaldehyde. It is used in the manufacture of melamine resins, laminates, surface coating resins, plastic molding compounds, textile resins, adhesives, gypsum-melamine resin mixtures, orthopedic plaster, rubber additives, and paper products. Human Exposure: Occupational exposure to melamine may occur during the production and use of melamine-formaldehyde synthetic resins. Animal Studies: The carcinogenicity of melamine was tested in mice and rats via oral feeding and in mice via skin smear testing. No treatment-related tumors were observed in mice after oral administration. Except for one rat, all male rats fed a melamine-containing diet developed transitional cell tumors in their bladders; all tumor-bearing animals had bladder stones, possibly containing melamine. The incidence of toxicity-related bladder hyperplasia in male mice fed a melamine-containing diet was observed. Twenty 6-week-old male Fisher 344 rats were divided into several groups and fed diets containing 99.4% melamine, with or without the addition of 10% sodium chloride, for 36 weeks. Rats were sacrificed at week 40. Bladder cancer was observed in all groups fed melamine alone and in the melamine plus sodium chloride group. No bladder cancer was observed in the melamine plus sodium chloride group. Sodium chloride significantly reduced the incidence of papillomas. Papillomas appeared in rats fed low-dose melamine alone compared to rats fed high-dose melamine alone and rats fed high-dose melamine plus sodium chloride alone. Tumor development was associated with the formation of stones (melamine urate) and papillomatosis. Male and female Fisher 344 rats and B6C3F1 mice were fed melamine in their diet for 103 weeks. The incidence of bladder stones in male rats in the high-dose group was 20%, while it was only 2% in the low-dose group. No bladder stones occurred in the control group. Bladder stones were present in 7 out of 8 bladders with transitional cell carcinoma and 3 out of 41 bladders without tumors. There was a statistically significant correlation between bladder stones and bladder tumors. 50% of melamine was recovered in urine within 6 hours after a single oral administration in rats. 90% of the dose was excreted in urine within 24 hours after a single oral administration of (14)-C-melamine to adult Fisher 344/N rats. Most of the radiolabeled substances were concentrated in the kidneys and bladder, with negligible amounts detected in exhaled breath and feces. The radiolabeled substances found in plasma and urine indicate that melamine is not metabolized in rats. Melamine can induce the production of λ phage (WP2s-λ) in Escherichia coli, but it cannot induce reversion mutations in Salmonella Typhimurium with or without an exogenous metabolic activation system. No sex-linked recessive lethal mutations were observed in fruit flies. Melamine did not induce gene-linked mutations in Salmonella typhimurium in vitro, nor did it induce sister chromatid exchange in Chinese hamster cells, or induce micronuclei in mouse bone marrow in vivo. Oral administration of melamine induced bladder and ureteral cancer in male rats, but only urinary tract hyperplasia in male mice. The occurrence of urinary tract tumors in male rats was closely associated with stone formation and exposure to higher doses. Other studies in male rats also confirmed dose-dependency, with concurrent administration of sodium chloride to increase urine output reducing tumor incidence. High doses of melamine (in male rats) induced bladder cancer. Bladder stone formation is a necessary condition for tumor induction. The continuous irritation of the bladder epithelium by stones can induce carcinogenesis; therefore, melamine only acts indirectly as a non-genotoxic carcinogen. (L1777)

---

Toxicity Data
LC50 (Rat) = 3,248 mg/m3
LD50: 3161 mg/kg (oral, rat) (L1777)
LD50: 3296 mg/kg (oral, mouse) (L1777)
LD50: > 1000 mg/kg (skin, rabbit) (L1777)
LC50: 3248 mg/m3 (inhalation, rat) (L1777)

---

Interactions
The major pet food recall associated with acute renal failure in dogs and cats initially listed melamine as a suspected toxic substance. During the investigation, cyanuric acid was also found in the problematic food in addition to melamine. This study aimed to assess the toxicity of melamine, cyanuric acid, and mixtures thereof to cats. In this preliminary study, 0.5% and 1% melamine were added to the diets of two cats, respectively. Over a 10-day period, cyanuric acid was added to the diet of one cat in escalating doses of 0.2%, 0.5%, and 1%. In each dose group, one cat was simultaneously fed 0%, 0.2%, 0.5%, and 1% melamine and cyanuric acid, respectively. No renal impairment was observed in cats fed melamine or cyanuric acid alone. Cats fed the mixture were euthanized 48 hours after administration due to acute renal failure. All cats fed the mixture showed the presence of fan-shaped birefringent crystals in urine and renal impressions. Histopathological findings were limited to the kidneys, including crystals primarily located in the distal renal tubules, severe interstitial edema, and hemorrhage at the corticomedullary junction. Estimated concentrations of melamine in the kidneys ranged from 496 to 734 mg/kg wet weight, and estimated concentrations of cyanuric acid ranged from 487 to 690 mg/kg wet weight. These results indicate that the combination of melamine and cyanuric acid is the cause of acute renal failure in the cats.

---

Non-human toxicity values
Mouse intraperitoneal injection LD50: 112 mg/kg body weight
Rabbit dermal administration LD50: >1000 mg/kg body weight
Male mouse gavage LD50: 3.3 g/kg
Female mouse gavage LD50: 7.0 g/kg
For more non-human toxicity values (complete data) for melamine (9 types in total), please visit the HSDB record page.

[1]. Melamine.

Melamine is a colorless to white monoclinic or prismatic crystal, or a white powder. It sublimates upon gentle heating. (NTP, 1992)
Melamine is a trimer of cyanamide with a 1,3,5-triazine skeleton. It is an exogenous metabolite functionally related to cyanamide. It is the conjugate base of melamine (1+).
Melamine has been reported in bees (Apis cerana), Euglena gracilis, and Aeromonas veronii, with relevant data available.
Melamine is an organic base, also a trimer of cyanamide, with a 1,3,5-triazine skeleton. Like cyanamide, it contains 66% (by mass) nitrogen. When mixed with resins, it releases nitrogen gas during combustion or carbonization, thus possessing flame-retardant properties and various other industrial applications. Melamine is also a metabolite of the insecticide cycloprothiazide. Melamine is formed in mammals that ingest cycloprozin. Cycloprozin has also been reported to be converted into melamine in plants. Melamine is described as harmful if swallowed, inhaled, or absorbed through the skin. Long-term exposure may lead to cancer or reproductive damage. It is irritating to the eyes, skin, and respiratory tract. However, its short-term lethal dose is comparable to that of ordinary table salt, with an LD50 of more than 3 grams per kilogram of body weight. [15] Scientists at the U.S. Food and Drug Administration (FDA) explained that when melamine and cyanuric acid are absorbed into the bloodstream, they concentrate and interact in the renal tubules filled with urine, then crystallize to form large numbers of round, yellow crystals that in turn block and damage the kidney cells lining the tubules, leading to kidney dysfunction.

C3H6N6

126.12

126.065

108-78-1

Melamine-15N3;287476-11-3;Melamine-13C3;1173022-88-2;Melamine-15N3,13C3;1246816-14-7

7955

White to off-white solid powder

1.7±0.1 g/cm3

557.5±33.0 °C at 760 mmHg

354 °C

325.3±12.6 °C

0.0±1.5 mmHg at 25°C

1.826

-1.37

3

6

0

9

63.3

0

N1C(N([H])[H])=NC(N([H])[H])=NC=1N([H])[H]

JDSHMPZPIAZGSV-UHFFFAOYSA-N

InChI=1S/C3H6N6/c4-1-7-2(5)9-3(6)8-1/h(H6,4,5,6,7,8,9)

1,3,5-triazine-2,4,6-triamine

Melamine NSC-2130 NSC2130NSC 2130

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 : ~12.5 mg/mL (~99.11 mM)
H2O : ~1 mg/mL (~7.93 mM)

Solubility in Formulation 1: ≥ 1.25 mg/mL (9.91 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 12.5 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.

---

Solubility in Formulation 2: ≥ 1.25 mg/mL (9.91 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 12.5 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.

---

View More

Solubility in Formulation 3: ≥ 1.25 mg/mL (9.91 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 12.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

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