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EC number: 202-498-7 | CAS number: 96-31-1
- 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:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: study in accordance with the OECD guideline 407 (1981)
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 993
- Report date:
- 1993
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Version / remarks:
- May 12, 1981
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: Guideline of the EEC Commission 84/449 of April 1984
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- testing laboratory
- Limit test:
- no
Test material
- Reference substance name:
- 1,3-dimethylurea
- EC Number:
- 202-498-7
- EC Name:
- 1,3-dimethylurea
- Cas Number:
- 96-31-1
- Molecular formula:
- C3H8N2O
- IUPAC Name:
- 1,3-dimethylurea
- Details on test material:
- - Name of test material (as cited in study report): N,N'-Dimethylurea (DMH)
- Substance No. : 90/88
- Physical state: solid / white
- Analytical purity: ≥ 96 %
- Storage condition of test material: room temperature
- Stability under test conditions: The stability of the test substance over the study period was proven by reanalysis. The stability of N,N'-Dimethylurea in the vehicle over a period of 10 days was verified analytically before the start of the study.
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Dr. Karl Thomae GmbH, Biberach/Riss, Germany
- Age at study initiation: 42 days
- Mean weight at study initiation: male animals 199 (191 - 212) g; female animals 149 (137 - 157) g
- Housing: singly
- Diet (e.g. ad libitum): Kliba rats/mice/ hamsters maintenance diet, "A" 343 meal, Klingentalmuehle AG, Kaiseraugst, Switzerland, ad libitum
- Water (e.g. ad libitum): drinking water ad libitum
- Acclimation period: 10 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24°C
- Humidity (%): 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12 h / 12 h
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Remarks:
- bidest
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
The doses were prepared once a week. The test substance was weighed and diluted to the appropriate volume with bidistilled water.
ADMINISTRATION VOLUME: 10 mL / kg body weight
VEHICLE
- Concentration in vehicle: 150; 500; 1500; 4500 mg/100 mL
OTHER INFORMATIONS
The doses were administered using syringes (5 ml, by Becton Dickinson and Co., USA) . - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- 2 samples of each concentration obtained at the beginning of the study were sent to the Central Analytical Laboratory. HPLC was used to determine the content of N,N'-Dimethylurea of the undiluted test substance preparations.
- Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- 5 days/week
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0; 15; 50; 150; 450 mg/kg bw
Basis:
actual ingested
- No. of animals per sex per dose:
- 5 animals
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Post-exposure period: none
- Rationale for animal assignment (if not random):
Before the start of the administration period the animals were distributed according to weight among the individual test groups separated by sex . The randomization list was drawn up by a computer (laboratory data processing, Department of Toxicology, BASF AG) - Positive control:
- no
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: General state of health of the animals and dead or moribund animals was checked twice a day on working days and once on Saturdays, Sundays and public holidays.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: before and after each test substance administration
BODY WEIGHT: Yes
- Time schedule for examinations: on day 0 (start of administration period) and thereafter in weekly intervals .
FOOD CONSUMPTION AND COMPOUND INTAKE:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/animal/day: Yes
HAEMATOLOGY: Yes
- Time schedule for collection of blood: 27 days after beginning of administration period
- Anaesthetic used for blood collection: No
- Animals fasted: No
- How many animals: 5 animals per test group and sex
- Parameters checked: leukocytes, erythrocytes, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelets
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Blood was taken from the retroorbital venous plexus in the morning
- Animals fasted: non-fasted, not anesthetized animals
- How many animals: 5 animals per test group and sex
- Parameters checked: Enzymes (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, serum-gamma-glutamyltransferase), Blood chemistry (sodium, potassium, chloride, inorganic phosphate, calcium, urea, creatinine, glucose, total bilirubin, total protein, albumin, globulins, triglycerides, cholesterol, magnesium)
URINALYSIS: Yes
- Time schedule for collection of urine: 26 days after beginning of administration period
- Metabolism cages used for collection of urine: Yes
- Animals fasted: No
- Parameters checked: colour, turbidity, nitrite, pH, protein, glucose, ketones, urobilinogen, bilirubin, blood, sediment - Sacrifice and pathology:
- NECROPSY: 29 days after beginning of administration period
GROSS PATHOLOGY: Yes - Statistics:
- Statistical analysis was performed for the clinical examinations, clinical chemistry and hematology and Urinalyses using the Kruskal-Wallis-test and the Mann-Whitney-U-test.
Results and discussion
Results of examinations
- Details on results:
- CLINICAL SIGNS AND MORTALITY: The administration of N,N'Dimethylurea at doses of 15, 50, 150 and 450 mg/kg body weight did not result in clinical signs related to the test substance administration in any of the animals participating the study.
No animal died intercurrently during the 4-weeks test period.
BODY WEIGHT AND WEIGHT GAIN: A significant lower body weight/body weight change of about -11 % and -29 % , respectively, could be seen in the male rats of the 450 mg/kg body weight group when compared to the control group during the whole study period.
The body weight/body weight gain of the female rats of test group 4 (450 mg/kg body weight) as well as of the male and female animals of the 15, 50 and 150 mg/kg bw groups did not differ significantly from the values of the vehicle control group .
FOOD CONSUMPTION: When compared to the untreated controls, the male and female rats of the dose groups 1 - 3 (15, 50, 150 mg/kg bw) showed no substance related differences regarding the amount of food consumed daily. (A significant increased food consumption on day 28 in the male rats of test group 3 was assessed as being incidental). In test group 4 (450 mg/kg body weight) the food consumption values were significantly decreased in both sexes during the first week of the study. Thereafter the food consumption reached the values of the untreated animals.
HAEMATOLOGY: No substance-induced changes were observed in the hematological parameters of both sexes. No substance-induced changes were observed in the clotting analyses of both sexes. No substance-induced changes were observed in the blood chemistry parameters of both sexes.
CLINICAL CHEMISTRY: No substance-induced changes were observed in the enzyme activities of both sexes.
URINALYSIS: At the end of the study an increase in renal tubular and transitional epithelial cells, which in some cases appeared in clusters, were found in the urine sediment of three males of the 450 mg/kg group. These findings are assessed to be treatment-related. The precence of these cell types in the urine indicates renal tubular damage or injury.
The other urine examinations revealed no changes which are due to the test substance administered.
GROSS PATHOLOGY: In groups 150 and 450 mg/kg bw renal alterations in male animals including tubular necrosis, desquamation of tubular epithelial cells and the presence of protein casts in tubular lumen were observed.
OTHER FINDINGS: There are some significant inter-group differences in the results of the hematological, clinicochemical and urinalytical data. These deviations are within the range of biological variation, inconsistent or lacking dosage-relationship. Accordingly, these changes are considered to be of no toxicological significance.
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 50 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male
- Dose descriptor:
- LOAEL
- Effect level:
- 150 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: renal alterations in male animals including tubular necrosis, desquamation of tubular epithelial cells and the presence of protein casts in tubular lumen
- Dose descriptor:
- NOAEL
- Effect level:
- 150 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- female
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Taking into account all findings above, the 4-week administration of N,N'-Dimethylurea caused substance-related changes in the kidneys at doses of 450 (males and females) and 150 (males only) mg/kg body weight.
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