Registration Dossier
Registration Dossier
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 253-575-7 | CAS number: 37640-57-6
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data

Repeated dose toxicity: oral
Administrative data
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
Data source
Reference
- Reference Type:
- publication
- Title:
- Nephrotoxic Potential and Toxicokinetics of Melamine Combined with Cyanuric Acid in Rats
- Author:
- Kim GH, Kang MJ, Noh K, Oh DG, Kang W, Jeong HG, Lee KY, Kim H, Kim HS, Jeong TC
- Year:
- 2 014
- Bibliographic source:
- Journal of Toxicology and Environmental Health, Part A, 77:1346–1358
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- 7-day oral toxicity study in rats, conducted to examine the effects of melamine (MEL) and cyanuric acid (CYA) (1:1) on kidneys
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Melamine
- EC Number:
- 203-615-4
- EC Name:
- Melamine
- Cas Number:
- 108-78-1
- Molecular formula:
- C3H6N6
- IUPAC Name:
- 1,3,5-triazine-2,4,6-triamine
- Reference substance name:
- Cyanuric acid
- EC Number:
- 203-618-0
- EC Name:
- Cyanuric acid
- Cas Number:
- 108-80-5
- Molecular formula:
- C3H3N3O3
- IUPAC Name:
- 1,3,5-triazine-2,4,6-triol
- Test material form:
- solid
- Details on test material:
- different mixtures of 108-78-1 and 108-80-5 from 1:1 to 3:1
Constituent 1
Constituent 2
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Orient Co., Seoul, Korea
- Age at study initiation: 7 weeks old
- Weight at study initiation: approximately 200 g
- Housing: 2 or 3 rats per cage
- Acclimation period: at least 1 week
ENVIRONMENTAL CONDITIONS
- Temperature: 23 ± 3 °C
- Humidity: 50 ± 10 %
- Photoperiod: 12 hours light / 12 hours dark
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: 0.3 % Tween 80 and 0.1 % CMC-Na in saline with 0.25 % 1 N HCl, pH 4.5
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
- MEL and CYA were each dissolved in the vehicle.
- Combination: MEL and CYA in half of the volume of vehicle were separately prepared and mixed 1:1.
VEHICLE
- Concentration in vehicle: 10 mg/mL
- Amount of vehicle: 10 mL/kg bw - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 7 days
- Frequency of treatment:
- once daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 4 mg/kg bw/day (nominal)
- Remarks:
- MEL and CYA (1:1)
- Dose / conc.:
- 20 mg/kg bw/day (nominal)
- Remarks:
- MEL and CYA (1:1)
- Dose / conc.:
- 100 mg/kg bw/day (nominal)
- Remarks:
- MEL and CYA (1:1)
- Dose / conc.:
- 100 mg/kg bw/day (nominal)
- Remarks:
- MEL
- Dose / conc.:
- 100 mg/kg bw/day (nominal)
- Remarks:
- CYA
- No. of animals per sex per dose:
- 3 to 5 rats
- Control animals:
- no
- Positive control:
- not required
Examinations
- Observations and examinations performed and frequency:
- MORTALITY: Yes
BODY WEIGHT: Yes
- Time schedule for examinations: daily
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: before each dosing, on Day 0, 1, 3, 7
- Anaesthetic used for blood collection: not specified
- Animals fasted: not specified
- How many animals: 3-5 rats per dose group and sampling timepoint
- Parameters examined: BUN, creatinine, total protein
TOXICOKINETIC INVESTIGATIONS: Yes
- Time schedule for collection of blood: before and 24, 48, 72, 96, 120, 144, and 168 hours after treatment start
- Concentrations of MEL and CYA were determined in serum, urine, and kidney tissues by means of liquid chromatography–mass spectrometry
URINALYSIS: Yes
- Time schedule for collection of urine: one day prior to treatment start and immediately after final dosing, urine was collected for 24 hours.
- Metabolism cages used for collection of urine: yes (1 rat per cage)
- Animals fasted: not specified
- Parameters examined: baseline exposure to MEL and/or CYA, urinary excretion, urine volume - Sacrifice and pathology:
- ORGAN WEIGHTS: Yes
Kidney, spleen, liver
HISTOPATHOLOGY: Yes
Kidney - Other examinations:
- DETERMINATION OF MEL AND CYA IN KIDNEYS: Yes
Determination of accumulated MEL and CYA was performed by LC-MS/MS. - Statistics:
- Mean ± standard error (SE)
Statistical significance:
- ANOVA followed by Dunnett’s t-test (significance at p < 0.05)
- Duncan’s multiple range tests, where applicable (significance at p < 0.05)
Results and discussion
Results of examinations
- Details on results:
- MORTALITY:
Two rats treated with 100 mg/kg bw/d MEL and CYA (1:1) were found dead (one rat on day 2, one rat on day 3).
BODY WEIGHTS:
Body weights were statistically significantly reduced at 20 and 100 mg/kg bw/d MEL and CYA (1:1).
CLINICAL CHEMISTRY:
BUN and creatinine were statistically significantly increased and total protein was statistically significantly reduced at 20 and 100 mg/kg bw/d MEL and CYA (1:1).
URINALYSIS:
After 7 days of dosing, MEL and CYA were present only in small amounts in urine of animals treated at 100 mg/kg bw/d MEL and CYA (1:1) as compared to levels determined in animals treated with either 100 mg/kg bw/d MEL or CYA. The combined dose of MEL and CYA (1:1) led to accumulation.
ORGAN WEIGHTS:
Kidney weights were statistically significantly increased at 20 and 100 mg/kg bw/d MEL and CYA (1:1).
The weights of spleen and liver were significantly decreased in these groups.
HISTOPATHOLOGY:
Renal histopathologic findings: Tubular dilatation, crystal deposition, granulomatous tubulo-interstitial inflammation, and tubular necrosis with regeneration were noted at 20 and 100 mg/kg bw/d MEL and CYA (1:1). There were no relevant microscopic findings in kidneys of animals treated at 4 mg/kg bw/d MEL and CYA (1:1) or at 100 mg/kg bw/d MEL. Minimal signs of crystal deposits were noted in 1/5 rats at 100 mg/kg bw/d CYA, together with tubular dilatation, tubular necrosis and pelvic epithelial hyperplasia.
TOXICOKINETIC INVESTIGATION:
MEL or CYA alone were eliminated almost completely within 24 hours after dosing showing no accumulation in kidney.
MEL and CYA (1:1) treatment produced marked accumulation of MEL and CYA in blood.
DETERMINATION OF MEL AND CYA IN KIDNEYS
After 7 days of treatment, significant amounts of MEL and CYA were accumulated in the kidneys.
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 4 mg/kg bw/day (nominal)
- Based on:
- other: MEL and CYA (1:1)
- Sex:
- male
- Basis for effect level:
- other: crystals of melamine cyanurate in kidneys
- Remarks on result:
- other: No dose descriptor was derived by the study authors
Any other information on results incl. tables
MEL and CYA (1:1) exposure produced renal toxicity, apparently due to significant chemical accumulation in kidney accompanied by low excretion.
Applicant's summary and conclusion
- Executive summary:
In a 7 day repeated dose toxicity study (Kim et al., 2014), groups of male rats were treated by oral gavage with a 1:1 mixture of melamine (MEL) and cyanuric acid (CYA). Additional groups received 100 mg/kg bw/d MEL or 100 mg/kg w/d CYA. A concurrent control group was treated with the vehicle (aqueous CMC/Tween 80) alone. Mortality, body weight, and clinical chemistry, urinalysis and toxicokinetic parameters were assessed. After scheduled necropsy selected organ weights were determined and the kidneys were examined microscopically. MEL and CYA contents were determined in homogenized kidneys. Only the combined exposure to MEL and CYA (1:1) induced nephrotoxicity. According to the results of this study, combined dosing at high dose levels might produce renal toxicity due to significant chemical accumulation in kidney accompanied by low excretion. Based on crystal formation in kidneys with associated nephrotoxicity and secondary changes in investigated parameters at 20 and 100 mg/kg bw/d MEL and CYA (1:1), a NOAEL of 4 mg/kg bw/d can be deemed for exposure to MEL and CYA (1:1) under the conditions of this study (no NOAEL was set by the study authors).
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.

EU Privacy Disclaimer
This website uses cookies to ensure you get the best experience on our websites.