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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Published NCI screening study: 12-month duration; limited investigations
Cross-reference
Reason / purpose:
reference to same study

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:
1980
Bibliographic source:
Journal of Environmental Pathology and Toxicology 3(5-6): 149-70

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: NCI screening study
Principles of method if other than guideline:
12 month screening carcinogenesis study, with limited assessment of toxicity
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Supplied by Aldrich: lot 082017

Test animals

Species:
mouse
Strain:
C57BL
Sex:
male/female
Details on test animals 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°Cand a 12-hour light/dark cycle was maintained. Diets were prepared weekly.

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
12 months
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
Control animals:
yes, plain diet
Positive control:
Not required

Examinations

Observations and examinations performed and frequency:
Animals were exposed to urea for 12 months, followed by a 4-month recovery period. Individual bodyweights were recovered pre-test and at termination. Cage weights were recorded weekly during the study.
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. All remaining animals were sacrificed after the 4-month recovery period and investigated histopathologically.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
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:
no effects observed
Details on results:
There were no signs of toxicity; bodyweights and survival were unaffected by treatment. Necropsy did not reveal any effects of treatment.

Effect levels

Dose descriptor:
NOAEL
Effect level:
45 000 ppm
Sex:
male/female
Basis for effect level:
other: No effects were observed at 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

No evidence of toxicity was seen in this study at dose levels of up to 45000 ppm.

Applicant's summary and conclusion

Conclusions:
Urea is of low toxicity following chronic administration to the mouse.
Executive summary:

In a 12 -month carcinogenicity screening assay, C57BL/6 mice (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 were investigated histopathologically; interim deaths were similarly investigated. All remaining animals were sacrificed after the 4-month recovery period and investigated histopathologically. There were no signs of toxicity. Survival and bodyweights were unaffected by treatment. Gross and microscopic pathology did not reveal any treatment-related effects. It is concluded that urea is of very low chronic toxicity.