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EC number: 247-728-7 | CAS number: 26479-35-6
- 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:
- chronic toxicity: oral
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Published U.S. National Cancer Institute screening study for chronic toxicity and carcinogenicity: 12-month exposure with 4-month recovery period; however, limited toxicological investigations.
Data source
Reference
- Reference Type:
- publication
- Title:
- Carcinogenesis bioassay of acetamide, hexanamide, adipamide, urea and P-tolylurea in mice and rats
- Author:
- Fleischman, R.W. Baker, J.R. Hagopian, M. Wade, G.G. Hayden, D.W. Smith, E.R. Weisburger, J.H. Weisburger, E.K.
- Year:
- 1 980
- Bibliographic source:
- Journal of Environmental Pathology and Toxicology 3(5-6): 149-70
Materials and methods
- Principles of method if other than guideline:
- 12-month screening carcinogenesis/chronic toxicity study followed by a 4-month recovery period with limited assessment of toxicological endpoints.
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Urea
- EC Number:
- 200-315-5
- EC Name:
- Urea
- Cas Number:
- 57-13-6
- Molecular formula:
- CH4N2O
- IUPAC Name:
- urea
- Test material form:
- solid: pellets
- Details on test material:
- Supplied by Aldrich: lot 082017
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Animals were obtained from Charles River and randomly assigned to dose groups. Animals were 6 weeks old when assigned to the study and were group housed (5/sex/cage). Food and water were available ad libitum. The mean ambient air temperature was 23 degrees C and a 12-hour light/dark cycle was maintained. Diets were prepared weekly.
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- DIET PREPARATION
- Rate of preparation of diet (frequency): once each week
- Mixing appropriate amounts with (Type of food): The test substance was initially formulated/prepared as a concentrated hand-blended premix. The mixture and remainder of the stock diet were then thoroughly blended in a Patterson-Kelley stainless steel Twin Shell V-Blender for 20-30 minutes.
- Storage temperature of food: Test diets were stored at 4 degrees C.
Stability studies on the test substance admixed with feed were performed on day 1 and day 14 using a colorimetric urea nitrogen method. The analytical results indicated the test substance was stable over a period of 14 days. Diet mixes older than two weeks were discarded. - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- Animals were exposed to urea for 12 months, followed by a 4-month recovery period.
- Frequency of treatment:
- Continuous (ad libitum)
Doses / concentrations
- Remarks:
- Doses / Concentrations:
4500, 9000, 45000 ppm
Basis:
nominal in diet
- No. of animals per sex per dose:
- 50/sex
- Details on study design:
- - Dose selection rationale: no data
- Rationale for animal assignment (if not random): the random casual method was used
- Rationale for selecting satellite groups: no satellite groups were used
- Post-exposure recovery period in satellite groups: not applicable
- Section schedule rationale (if not random): not applicable
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: No data
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Twice daily
BODY WEIGHT: Yes
- Time schedule for examinations: Individual bodyweights were recorded pre-test and at study termination. Cage weights were recorded weekly during the study.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: No
CLINICAL CHEMISTRY: No
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- Five animals/sex/group were sacrificed at the end of the 365-day exposure period and a comprehensive list of tissues were investigated histopathologically; interim deaths were similarly investigated. Brain, lung, trachea, heart, thymus, pituitary, thyroids, parathyroids, adrenals, esophagus, stomach, duodenum, jejunum, ileum, colon, liver, spleen, lymph nodes, bone and bone marrow, skin, salivary and mammary glands were collected and fixed in 10% neutral buffered formalin. Tissues were paraffin embedded, cut at 4-6 um, stained with H&E, and examined microscopically to determine presence of neoplastic/preneoplastic changes or signs or any toxic syndrome.
All remaining animals were sacrificed after the 4-month recovery period and investigated histopathologically. - Statistics:
- The purpose of the statistical analysis of tumors was to determine whether animals receiving test substance developed a significantly (P<0.05) different proportion of tumors than control animals. Statistical analyses of the incidences of specific types of tumors were made using the Fisher exact test to compare each control group with each group of treated animals at each dose. If more than one dose level of test substance was used, the Cochran-Armitage test for linear trend in proportions with continuity correction was used.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- The mid-dose group of male rats showed decreased survival (89%) relative to diet controls (95%).
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- The mid-dose group of male rats showed decreased survival (89%) relative to diet controls (95%).
- Body weight and weight changes:
- no effects observed
- 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
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Among the high dosed rats, there was a statistically significant increase in incidence of interstitial cell adenomas of the testes.
- Details on results:
- The lesion of interstitial cell adenomas of the testes found in the high dose group males may occur in 100% of controls (historically); thus, its biological significance is questionable according to the study authors.
There were no bodyweight effects. The decreased survival of the mid-dose group males had no dose-relationship as survival of all other test groups remained unaffected by treatment.
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 45 000 ppm
- Sex:
- male/female
- Basis for effect level:
- other: No dose-related, biologically significant adverse effects were attributable to the test substance up to the highest dose level (4.5% in the diet)
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Based on the limited toxicological endpoints evaluated in this study, there were no dose-dependent, biologically significant carcinogenic or toxic effects at dose levels of up to 45000 ppm.
Applicant's summary and conclusion
- Conclusions:
- In this study with limited evaluation of toxicological endpoints, chronic administration of urea to the rat produced no dose-dependent, biologically significant chronic or carcinogenic effects that could be clearly attributable to the test substance.
- Executive summary:
In a 12-month carcinogenicity/chronic screening assay, Fischer 344 rats (50/sex/group) were exposed to urea in the diet at concentrations of 4500, 9000 or 45000 ppm for 12 months. Five animals/sex/group were sacrificed at the end of the 365-day exposure period and a comprehensive list of tissues was investigated histopathologically; interim deaths were similarly investigated. All remaining animals were sacrificed after the 4-month recovery period and investigated histopathologically. There were no clear dose-dependent signs of chronic toxicity based on the limited toxicological assessment; bodyweights were unaffected by treatment, while only the mid-dose group of males had reduced survival. Gross and microscopic pathology did not reveal dose-dependent, biologically significant adverse effects (chronic or carcinogenic). This study concluded that urea is non-carcinogenic and of low chronic toxicity.
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