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EC number: 201-051-3 | CAS number: 77-71-4
- 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:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study performed to GLP and guideline.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 991
- Report date:
- 1991
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- EPA OPP 82-1 (90-Day Oral Toxicity)
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- 5,5-dimethylhydantoin
- EC Number:
- 201-051-3
- EC Name:
- 5,5-dimethylhydantoin
- Cas Number:
- 77-71-4
- Molecular formula:
- C5H8N2O2
- IUPAC Name:
- 5,5-dimethylimidazolidine-2,4-dione
- Reference substance name:
- dimethylhydantoin
- IUPAC Name:
- dimethylhydantoin
- Details on test material:
- - Name of test material (as cited in study report): Dimethylhydantoin
-Physical state: white crystals
-Analytical purity: >99.5%
-Lot/batch No.: F9431299
-Storage condition of test material: room temperature
Constituent 1
Constituent 2
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Test animals
Source: Charles River Breeding Laboratories, Kingston, New York
Age at study initiation: 7 weeks old
Weight at study initiation: Male: 204.5 to 270.3 g - Female: 161.7 to 214.1 g
Housing: individually housed during experiment. Group housed (2-3 per cage) during acclimation period.
Diet: ad libitum
Water: ad libitum
Acclimation period: 14 days
Environmental conditions:
Temperature (°C): 68-76 °C.
Humidity (%): 40-70 %
Photoperiod (hrs dark / hrs light): 12 hours dark and 12 hours light
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The samples were diluted and analysed by HPLC. Analyses of samples at the 1% and 10% nominal concentration levels demonstrated homogeneity. Concentration verififcation analyses were within 9 % of the target value.
HPLC parameters:
Column: Alltech Absorbosphere C8, 25cm x 4.6 mm, 10 micron particle size.
Mobile phase: 70% water / 30% acetonitrile
Detector: waters Associates UV 450 Variable Wavelength/LDC SM4000 Multi-wavelength UV
Pump: Waters Corporation 510
Integrator: Hewlett-Packard HP3396A/Waters Associates Baseline 810 Computer system
Autosampler: waters corporation WISP 710B
Injection size: 5 microliters / 10 microliters
Chart speed 0.5 / 1.0 cm/min
Flow rate: 0.8 ml/min isocratic
Attenuation: 2^10 - Duration of treatment / exposure:
- 90 days (13 weeks)
- Frequency of treatment:
- 5 days per week
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
100 mg/kg
Basis:
nominal in water
- Remarks:
- Doses / Concentrations:
300 mg/kg
Basis:
nominal in water
- Remarks:
- Doses / Concentrations:
1000 mg/kg
Basis:
nominal in water
- No. of animals per sex per dose:
- 15/sex/dose
- Control animals:
- yes, concurrent vehicle
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
Time schedule: once daily
DETAILED CLINICAL OBSERVATIONS: Yes
Time schedule: weekly
BODY WEIGHT: Yes
Time schedule for examinations: weekly
WATER CONSUMPTION: No
FOOD CONSUMPTION: Yes
Time schedule for examinations: weekly
HAEMATOLOGY: Yes
Time schedule for collection of blood: end of study
How many animals: first ten surviving animals/sex/group examined at necropsy
Parameters checked: Haematocrit, haemoglobin concentration, erythrocyte count, total and differential leukocyte count, platelet count
CLINICAL CHEMISTRY: Yes
Time schedule for collection of blood: end of study
How many animals: first ten surviving animals/sex/group examined at necropsy
Parameters checked: sodium, potassium, chloride, glucose, calcium, globulin (calculated), blood urea nitrogen, total bilirubin, creatinine, total protein, albumin, alanine aminotransferase, aspartate aminotransferase, phosphorous, alkaline phosphatase, gamma glutamyl transferase, A/G ratio (calculated)
URINALYSIS: No
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: Prior to study initiation and during final week of study
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY:
Performed on all animals. The necropsy included: brain, spinal cord, pituitary, thyroid, parathyroid, thymus, oesophagus, salivary glands, stomach, sternum with marrow, small and large intestines, liver, pancreas, kidneys, adrenals, spleen, heart, trachea, lungs, aorta, uterus, mammary glands, prostate, urinary bladder, lymph nodes, skin, eye.
HISTOPATHOLOGY:
Histopathology performed on first 10 surviving animals/sex/dose level. - Statistics:
- Bartletts test was used to determine if dose groups had equal variance.
Parametric procedures used one way ANOVA using F distribution If significant differences were seen Dunnett’s test was used to determine which treatment groups differed significantly from the control.
For non parametric procedures test of equality of means was performed using Kruskal-Wallis test. If significant differences were seen Dunn’s Summed Rank test was used to determine which treatment groups differed significantly from the control.
In addition Jonckheere’s test for monotonic trend in the dose response was performed.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- CLINICAL SIGNS
Sporadic evidence of alopecia, missing/broken/maloccluded incisors and red/clear ocular discharge.
MORTALITY
One male in the control group was euthanized on day 41 because of a broken snout. One female in the 300 mg/kg dose group was found dead on day 74 due to miss-dosing.
BODY WEIGHT GAIN
Decreased body weight gain in male rats in the high dose group.
Increased body weight in females in all treatment groups.
FOOD CONSUMPTION AND COMPOUND INTAKE
Reduction in food consumption in the high dose male rats.
OPHTHALMOSCOPIC EXAMINATION
No effects
HAEMATOLOGY
No effects
CLINICAL CHEMISTRY
No effects
URINALYSIS
Not conducted
NEUROBEHAVIOUR
Not examined
ORGAN WEIGHTS
The mean absolute and relative liver weights for male rats in the high dose group were decreased. The mean absolute and relative liver weigh values for females were increased in the high dose group. The mean absolute kidney weights were also increased in the high dose females but was considered to be a reflection of the increased body weight.
GROSS PATHOLOGY AND HISTOPATHOLOGY (NON-NEOPLASTIC)
Abnormalities noted at very low incidences included entire GI tract distended with gas, emaciation, smaller than normal seminal vesicles, clear yellow liquid in stomach, distended uterus, larger than normal ovaries, liver mass, liver thickening, lung discoloration and distended cecum. None of these appeared to be related to the treatment.
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- > 1 000 mg/kg bw/day (nominal)
- Sex:
- male/female
- Basis for effect level:
- other: Based upon the observation of no-effects related to treatment on any studied parameters.
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- The results of this thirteen week oral gavage study indicate that dimethylhydantoin has little or no potential to produce toxic effects when administered to rats at dosages as high as 1000 mg/kg/day. The NOAEL is therefore determined to be > 1000 mg/kg.
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