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EC number: 203-615-4 | CAS number: 108-78-1
- 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:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: NTP studies are considered as high quality studies, even if GLP was formally not stated and some standard methods were not applied. The studies are peer reviewed. The test substance was analysed extensively.
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
Reference
- Endpoint:
- repeated dose toxicity: oral, other
- Remarks:
- combined repeated dose and carcinogenicity
- Type of information:
- other: re-evaluation of data
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Studies for NTP are usually of high standard. The study has one specific aim, therefore not meeting the full requirements of a guideline study.
- Reason / purpose for cross-reference:
- reference to other study
- Qualifier:
- no guideline required
- Principles of method if other than guideline:
- The histopathologic changes induced in F344 rat kidney by oral administration of melamine for 13-week and 2-year periods in studies conducted by the National Toxicology Program, NIH, from 1976 to 1983 (see "NTP 1983" under sections 7.5.1 and 7.7) have been re-evaluated and described in detail.
- GLP compliance:
- not specified
- Species:
- rat
- Strain:
- Fischer 344
- Route of administration:
- oral: feed
- Details on oral exposure:
- As in "NTP 1983".
- Observations and examinations performed and frequency:
- Histopathologic changes have been re-evaluated.
- Clinical signs:
- not examined
- Mortality:
- not examined
- Body weight and weight changes:
- not examined
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- The reflux nephropathy was observed in the high dosed (12000 and 18000 ppm) animals of the two 13-week studies with one exception in the 6000 ppm group. It was observed at 2250 ppm and higher in the 2-years study.
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- not examined
- Details on results:
- A constellation of tubule changes extending from papilla to cortex consistently included tubule dilatation and tubule basophilia as salient features at the subchronic time point. By 2 years, these lesions had usually resolved into fibrotic scars, in which tubule loss and collagen deposition were prominent, running from superficial cortex into the medulla. These fibrotic lesions required discrimination from chronic scars resulting from infarcts and foci of chronic progressive nephropathy (CPN). A case is presented here for interpreting the constellation of histologic changes induced in rats by melamine as representing an ascending form of nephropathy. The term retrograde nephropathy is considered to be appropriate nomenclature for both the acute and chronic lesions. The cause for the reflux, emanating from the lower urinary tract, appeared not to be infection as an inflammatory response was not prominent.
The reflux nephropathy was observed in the high dosed (12000 and 18000 ppm) animals of the two 13-week studies with one exception in the 6000 ppm group. It was observed at 2250 ppm and higher in the 2-years study. - Key result
- Dose descriptor:
- LOAEL
- Effect level:
- 12 000 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: For the two 13-weeks studies.
- Key result
- Dose descriptor:
- LOAEL
- Effect level:
- 2 250 ppm
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: For the 2-years study.
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 2 250 ppm
- System:
- urinary
- Organ:
- kidney
- Treatment related:
- yes
- Dose response relationship:
- yes
- Relevant for humans:
- yes
- Conclusions:
- Kidney lesions, detected in the tissues of the NTP 1983 study at higher doses (compared to uroliths), are described.
- Executive summary:
The histopathologic changes induced in F344 rat kidney by oral administration of melamine for 13 -week and 2 -year periods in studies conducted by the National Toxicology Program, NIH, from 1976 to 1983 have been re-evaluated and described in detail.
A constellation of tubule changes extending from papilla to cortex consistently included tubule dilatation and tubule basophilia as salient features at the subchronic time point. By 2 years, these lesions had usually resolved into fibrotic scars, in which tubule loss and collagen deposition were prominent, running from superficial cortex into the medulla. These fibrotic lesions required discrimination from chronic scars resulting from infarcts and foci of chronic progressive nephropathy (CPN). A case is presented here for interpreting the constellation of histologic changes induced in rats by melamine as representing an ascending form of nephropathy. The term retrograde nephropathy is considered to be appropriate nomenclature for both the acute and chronic lesions. The cause for the reflux, emanating from the lower urinary tract, appeared not to be infection as an inflammatory response was not prominent. It can be speculated that melamine precipitation in the lower urinary tract created pressure effects through transient obstruction leading to the renal changes. These changes were different from those involved in a major US outbreak of renal disease and death in cats and dogs associated with triazine-contaminated pet food, in which crystalluria from insoluble melamine/cyanuric acid complexes occurred in the kidney. However, the rat findings may be relevant to melamine-associated kidney disease recently reported in infants in China.
Data source
Referenceopen allclose all
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 983
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 984
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: NTP standards
- Deviations:
- yes
- Remarks:
- No haematology and clinical chemistry investigations were performed. No statistical analysis was reported or performed.
- Principles of method if other than guideline:
- Three 13 weeks toxicity studies were performed:
In the first 13-week study, diets containing 0, 6000, 9000, 12000, 15000, or 18000 ppm melamine were fed to groups of 12 male and 12 female rats and to groups of 10 male and 10 female mice for 13 weeks.
Two additional 13-week studies were conducted to find a no-effect level for urinary bladder stone formation and to determine the effect of ammonium chloride in the drinking water on stone formation.
In the second 13-week study, groups of 10 rats of either sex were fed diets containing 0, 750, 1500, 3000, 6000, or 12000 ppm melamine for 13 weeks; At day 65, five rats of either sex fed 750 ppm melamine and two control rats of each sex were placed in metabolism cages and fasted overnight. Urine samples collected from each cage were centrifuged and the sediment fractions were examined microscopically.
In a third 13-week study, groups of 10 rats of either sex were fed diets containing 0, 10000, or 18000 ppm melamine in the presence and absence of 1 % ammonium chloride in the drinking water. - 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
- Details on test material:
- - Name of test material (as cited in study report): melamine.
- Analytical purity: Results of purity and identity analyses conducted at Midwest Research Institute (MRI) indicated that both lots were similar in purity in all respects.
Results of elemental analyses for both lots agreed with the theoretical values. Titration of one amino group indicated that both lots were approximately 100 % ± 1 % pure. For both lots, only one spot was detected by thin-layer chromatography.
- Impurities (identity and concentrations): Several minor impurities were detected in both lots by high-performance liquid chromatography (HPLC). The impurities were not further characterized, but 6-amino-s-triazine-2,4-diol and 4,6-diamino-s-triazine- 2-ol are reported to be common impurities in melamine.
The differences in purity determined by HPLC and titration could be due to impurities with titratable amine groups, such as the impurities mentioned above, that would result in an apparently high titration value. In addition, the detector response in HPLC is highly dependent upon the absorbance of the substance at the detector wavelength used. The values reported are absolute areas expressed as percentages of the area of the major peak and do not take into account the different values of the compound and its impurities at 254 nm. Therefore, the relative areas determined by HPLC do not necessarily reflect the actual weight percentages of the impurities in the sample.
- The infrared and ultraviolet spectra of both lots were consistent with the literature spectra.
- Lot/batch No.: Technical-grade melamine was obtained in two batches from American Cyanamid Company (Bound Brook, NJ).
Lot No. A7-11-75 was used for the single-dose and prechronic studies and for the first 14 months of the chronic study.
Lot No. A13179 was used for the remainder of the chronic studies.
- Stability under test conditions: The chemical was stable at 60 °C for 2 weeks and therefore required no special storage temperature.
- Storage condition of test material: The chemical was stored at 4 °C throughout the study, and periodic analyses by thin-layer chromatography and infrared spectroscopy indicated that no significant degradation occurred over the lifetime of the study.
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Frederick Cancer Research Center, Frederick, MD
- Age at study initiation: 5 - 6 weeks.
- Housing: Rats were housed four per cage in polycarbonate cages covered with nonwoven polyester filter sheets. Racks and filters were changed once every 2 weeks. Cages, bedding, and glass water bottles (equipped with stainless steel sipper tubes) were replaced twice per week.
- Diet: Purina Laboratory Chow. Ralston Purina Co. Stainless steel feed containers were changed once per week.
- Water:
First and second studies: Tap water (acidified with hydrochloric acid to pH 2.5).
Third study: ± 1 % ammonium chloride in drinking water.
Test diets, control diets, and tap water were available ad libitum.
- Bedding: Absorb-Dri heat-treated hardwood chips, changed twice per week.
- Acclimation: 2 weeks
- Randomization: Animals assigned to cages by species and sex such that the cage weighs were approximately the same.
ENVIRONMENTAL CONDITIONS
- Temperature, humidity: The temperature in the animal rooms was 22 °- 26 °C and the relative humidity was 30 %-70 %.
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- DIET PREPARATION
- Mixing appropriate amounts with: Test diets were prepared by first mixing a small amount of Purina B Lab Chow and the required amount of melamine with a mortar and pestle and then adding this premix to the required amount of animal meal and mixing for 10 to 30 minutes in a Patterson-Kelly@ twinshell blender equipped with an intensifier bar.
- Storage temperature of food: Test diets were stored at 4 °C for no longer than 2 weeks. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- - Prepared diets containing 100 000 ppm melamine were analyzed and were found to be stable for 2 weeks at temperatures up to 45 °C.
Control animals were fed Purina Lab Chow. - Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- continuously
Doses / concentrationsopen allclose all
- Remarks:
- First study: 0, 6000, 9000, 12000, 15000 or 18000 ppm melamine in the diet for rats of bothe sexes. Basis: nominal in diet. The estimated melamine consumption in mg/ kg/ day for each animal was: 0, 560, 850, 1100, 1400, or 1700 for male rats; 0, 560, 880, 1200, 1400 or 1600 for female rats; according to Table 1 of NTP 1983.
- Remarks:
- Second study: 0, 750, 1500, 3000, 6000 or 12000 ppm for bothe sexes. Basis: nominal in diet
The estimated melamine consumption in mg/ kg/ day for each animal was: 0, 72, 150, 300, 590, or 1300 for male rats and 0, 84, 150, 300, 600, or 1300 for female rats, according to Table 1 of NTP 1983.
- Remarks:
- Third study: 0, 10000 or 18000 ppm. Basis: nominal in diet.
- No. of animals per sex per dose:
- FIRST STUDY
- 12 males/12 females
SECOND STUDY
- 10 males/10 females
THIRD STUDY
- 10 males/10 females - Control animals:
- yes, concurrent no treatment
- Details on study design:
- Post-exposure period: none
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily for mortality and signs of morbidity.
DETAILED CLINICAL OBSERVATIONS: No
BODY WEIGHT: Yes
- Time schedule for examinations: weekly.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Time schedule for examinations: weekly.
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No
OPHTHALMOSCOPIC EXAMINATION: No
URINALYSIS: Yes (only study No. 2)
-control animals: 1 male, 2 females.
- low dosed animals (750 ppm): all animals.
HAEMATOLOGY: No
CLINICAL CHEMISTRY: No
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No
- Sacrifice and pathology:
- GROSS PATHOLOGY (study No. 1 - 3): Yes (all animals)
HISTOPATHOLOGY (study No. 1): Yes (all animals control group (0 ppm) and highest dosed group (18000 ppm).
-gross lesions, tissue masses
-abnormal lymph nodes
-skin
-mandibular lymph nodes
-mammary glands
-salivary gland
-thigh muscle
-sciatic nerve
-bone marrow
-costochondral junction (rib)
-thymus
-larynx
-trachea
-lungs and bronchi
-heart
-thyroid
-parathyroid
-oesophagus
-stomach
-duodenum
-jejunum
-colon
-mesenteric lymph nodes
-liver
-pancreas
-spleen
-kidneys
-adrenals
-urinary bladder
-seminal vesicles
-prostate
-testes
-ovaries
-uterus
-nasal cavity
-brain
-pituitary
all animals low dose (6000 ppm) group:
-kidney
-urinary bladder
HISTOPATHOLOGY (study No. 2): Yes (all animals)
-kidney
-urinary bladder
HISTOPATHOLOGY (study No. 3): No - Statistics:
- not reported.
Results and discussion
Results of examinations
- Clinical signs:
- not specified
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- Study 1: One male rat receiving 18,000 ppm and two males receiving 6,000 ppm died.
Study 2: None of the rats died. - Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Study 1: Mean body weight gain in males and females receiving 12000 ppm or more was depressed by more than 8% when compared with controls.
Study 2: Mean body weight gain was depressed by more than 10% when compared with controls for male rats receiving 6,000 and 12,000 ppm, but no depression was observed in any group of dosed females. - Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Study 1: Feed consumption by rats receiving 18000 ppm was approximately 80%-90% that of controls.
Study 2: Feed consumption was not affected by incorporation of melamine in the feed. - Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- no effects observed
- Description (incidence and severity):
- Study 2: There were no differences in the urine samples that could be attributed to the presence of melamine in the feed. Microscopic examination of the urine did not provide any evidence of melamine crystalluria.
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Study 1: Stones were found in the urinary bladders of most dosed male rats, and the incidence was dose related. Twenty-five percent (3/ 12) or more females in the two highest dosed groups had stones.
Study 2: Other than stones in the bladder of dosed male rats, no compound-related effects were observed at necropsy. The incidence of stones in the urinary bladder of male rats was dose related. - Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Study 1: Histopathologic evaluations were performed on 10 animals of either sex from the high-dose (18,000 ppm), low-dose (6,000 ppm), and control groups. Diffuse epithelial hyperplasia of the urinary bladder was found in 8/ 10 males and 2/ 10 females receiving 18,000 ppm melamine, while in animals receiving 6,000 ppm melamine, focal epithelial hyperplasia was observed in only 1 / 10 males and in none of the females. The urinary bladders of animals from other dosed groups were not examined microscopically. No other compound-related histopathologic effects were observed.
Study 2: Stones were present even in the male group receiving 750 ppm. Hyperplasia of the transitional epithelium of the bladder was present in 1/10 male rats receiving 3,000 ppm, in 3/10 receiving 6,000 ppm, and in 919 receiving 12,000 ppm melamine. The hyperplastic epithelial changes, which were found only in male rats that had bladder stones, were accompanied by prominent capillaries and occasional edema and scattered mast cells in the submucosa. Kidney changes in male rats were minimal. There was no evidence of urinary bladder stones or hyperplasia of the bladder epithelium in any groups of dosed female rats, but dose-related calcareous deposits were observed in the straight segments of the proximal tubules in female rats (2/10 controls, 3/ 10 receiving 750 ppm, 4/ 10 receiving 1,500 ppm, 10/ 10 receiving 3,000 ppm, 8/ 10 receiving 6,000 ppm, and 10/ 10 receiving 12,000 ppm melamine). - Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- not specified
- Details on results:
- STUDY No. 1:
CLINICAL SIGNS AND MORTALITY
One male rat receiving 18,000 ppm and two males receiving 6,000 ppm died .
(See Table 4)
BODY WEIGHT AND WEIGHT GAIN
Mean body weight gain in males and females receiving 12,000 ppm or more was depressed by more than 8% when compared with controls.
(See Table 4)
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
Feed consumption by rats receiving 18,000 ppm was approximately 80%-90% that of controls.
GROSS PATHOLOGY
Stones were found in the urinary bladders of most dosed male rats, and the incidence was dose related. Twenty-five percent (3/ 12) or more females in the two highest dosed groups had stones.
HISTOPATHOLOGY: NON-NEOPLASTIC
Histopathologic evaluations were performed on 10 animals of either sex from the high-dose (18,000 ppm), low-dose (6,000 ppm), and control groups. Diffuse epithelial hyperplasia of the urinary bladder was found in 8/ 10 males and 2/ 10 females receiving 18,000 ppm melamine, while in animals receiving 6,000 ppm melamine, focal epithelial hyperplasia was observed in only 1 / 10 males and in none of the females. The urinary bladders of animals from other dosed groups were not examined microscopically. No other compound-related histopathologic effects were observed.
STUDY No. 2:
CLINICAL SIGNS AND MORTALITY
None of the rats died.
BODY WEIGHT AND WEIGHT GAIN
Mean body weight gain was depressed by more than 10% when compared with controls for male rats receiving 6,000 and 12,000 ppm, but no depression was observed in any group of dosed females.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
Feed consumption was not affected by incorporation of melamine in the feed.
URINALYSIS
There were no differences in the urine samples that could be attributed to the presence of melamine in the feed. Microscopic examination of the urine did not provide any evidence of melamine crystalluria.
GROSS PATHOLOGY
Other than stones in the bladder of dosed male rats, no compound-related effects were observed at necropsy. The incidence of stones in the urinary bladder of male rats was dose related.
HISTOPATHOLOGY: NON-NEOPLASTIC
Stones were present even in the male group receiving 750 ppm. Hyperplasia of the transitional epithelium of the bladder was present in 1/10 male rats receiving 3,000 ppm, in 3/10 receiving 6,000 ppm, and in 919 receiving 12,000 ppm melamine. The hyperplastic epithelial changes, which were found only in male rats that had bladder stones, were accompanied by prominent capillaries and occasional edema and scattered mast cells in the submucosa. Kidney changes in male rats were minimal. There was no evidence of urinary bladder stones or hyperplasia of the bladder epithelium in any groups of dosed female rats, but dose-related calcareous deposits were observed in the straight segments of the proximal tubules in female rats (2/10 controls, 3/ 10 receiving 750 ppm, 4/ 10 receiving 1,500 ppm, 10/ 10 receiving 3,000 ppm, 8/ 10 receiving 6,000 ppm, and 10/ 10 receiving 12,000 ppm melamine).
STUDY No. 3:
CLINICAL SIGNS AND MORTALITY
None of the rats died.
BODY WEIGHT AND WEIGHT GAIN
Rats fed diets containing 18,000 ppm melamine plus 1% ammonium chloride in the drinking water had decreased weight gains relative to groups receiving drinking water acidified with hydrochloric acid.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
There were no effects.
GROSS PATHOLOGY
The addition of ammonium chloride in the drinking water had no apparent effect on the incidence of urinary bladder stones in male or female rats. Urinary bladder stones were seen in 8/8 males and 3/9 females in the group that received 18,000 ppm melamine in feed plus 1% ammonium chloride in drinking water, compared with 10/ 10 males and 3/10 females in the groups administered 18,000 ppm melamine in feed without 1% ammonium chloride in the water. No other compound-related effects were observed at necropsy.
Effect levels
open allclose all
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 750 ppm
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- gross pathology
- other: 2 urinary bladder stones were detected compared to 1 in the control group. Statistically, 750 ppm is the NOAEL.
- Dose descriptor:
- NOAEL
- Effect level:
- 72 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: 2 urinary bladder stones were detected compared to 1 in the control group. Statistically, 750 ppm is the NOAEL.
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 6 000 ppm
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- body weight and weight gain
- other: body weight
- Dose descriptor:
- NOAEL
- Effect level:
- 600 mg/kg bw/day (nominal)
- Sex:
- female
- Basis for effect level:
- other: body weight
Target system / organ toxicity
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 1 500 ppm
- System:
- urinary
- Organ:
- bladder
- Treatment related:
- yes
- Dose response relationship:
- yes
- Relevant for humans:
- yes
Any other information on results incl. tables
The relevant results in the tables of the study are assembled in the attachment.
Applicant's summary and conclusion
- Conclusions:
- Most noticeable was the development of uroliths (urinary bladder stones) at 750 ppm and higher doses, mainly in males.
- Executive summary:
Melamine (2,4,6-triamino-s-triazine) was administered in the diet to F344 rats or B6C3F1 mice for 13 weeks (subchronic) to determine its toxicologic profile. The dose levels of melamine in the subchronic studies ranged from 750 to 18000 ppm for rats, and 6000 to 18000 ppm for mice. In these studies, compound-related lesions were observed in the urinary tract. Most noticeable was the development of uroliths (urinary bladder stones), which occurred at a greater frequency in males than females of either species. Increased incidences of urinary bladder stones and hyperplasia of the bladder epithelium were observed at 13 weeks in male rats fed diets containing melamine.
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