Urea

Repeated dose toxicity: oral

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 for cross-reference:

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

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

Test material information

Constituent 1

Reference substance name:

Urea

EC Number:

200-315-5

EC Name:

Urea

Cas Number:

57-13-6

Molecular formula:

CH4N2O

IUPAC Name:

urea

Details on test material:

Supplied by Aldrich: lot 082017

Test animals

Species:

mouse

Strain:

C57BL

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°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.