Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: other route
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Secondary source; report cited in WHO JECFA evaluation

Data source

Referenceopen allclose all

Reference Type:
review article or handbook
Title:
Urea
Author:
Olsen, P.
Bibliographic source:
WHO / JECFA Monograph 798: urea (WHO Food Additives Series 32)
Reference Type:
publication
Title:
Chronic urea intoxication in dogs
Author:
Balestru, P.L., Rindi, P. & Biagin, M.
Year:
1971
Bibliographic source:
Experimentia 27: 811-812

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Investigation of the subchronic subcutaneous toxicity of urea in the dog
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
No information available

Test animals

Species:
dog
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
12 dogs unilaterally nephrectomised

Administration / exposure

Route of administration:
subcutaneous
Vehicle:
not specified
Details on exposure:
Urea injected subcutaneously every 8 hours for 45 days
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Urea was administered for 45 days
Frequency of treatment:
Urea was administered every 8 hours
Doses / concentrations
Remarks:
Doses / Concentrations:
3000 - 4000 mg/kg bw
No. of animals per sex per dose:
12 animals total
Control animals:
not specified
Details on study design:
12 dogs unilaterally nephrectomised injected with urea subcutaneously every 8 hours for 45 days

Examinations

Observations and examinations performed and frequency:
Plasma urea levels, behaviour, urine output, blood
Sacrifice and pathology:
No information available
Other examinations:
No information available
Statistics:
No information available

Results and discussion

Results of examinations

Clinical signs:
not specified
Mortality:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Clinical biochemistry findings:
not specified
Urinalysis findings:
effects observed, treatment-related
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings: neoplastic:
not specified
Details on results:
Administration of urea led to increased diuresis, plasma urea levels were 200 - 700 mg/100ml. The dogs displayed mild drowsiness. Hematocrit, platelect counts and EEG were not affected.

Effect levels

Dose descriptor:
conc. level: 10% urea solution (3000-4000 mg/kg bw)
Sex:
male/female
Basis for effect level:
other: Low toxicity: causes increased diuresis and increased drowsiness.
Remarks on result:
not measured/tested
Remarks:
Effect level not specified (migrated information)

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Administration of urea led to increased diuresis, plasma urea levels were 200 - 700 mg/100ml. The dogs displayed mild drowsiness. Haematocrit, platelet counts and EEG were not affected.

Applicant's summary and conclusion

Conclusions:
The study indicates that urea is of very low toxicity in the dog following repeated administration.
Executive summary:

Twelve unilaterally nephrectomized dogs were injected subcutaneously with 10% urea solution (3000-4000 mg/kg bw) every 8 hours over a period of 45 days. Administration led to increased diuresis, plasma urea levels were 200 - 700 mg/100ml. The dogs displayed mild drowsiness. Haematocrit, platelet counts and EEG were not affected. The study indicates that urea is of very low toxicity in the dog following repeated administration.