Registration Dossier

Toxicological information

Repeated dose toxicity: dermal

Currently viewing:

Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Published literature study.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Toxicological Studies of Urea. Acute, Subacute and Chronic tests in Rats and Mice.
Author:
Sato, N., Aikawa, K., Sugimoto, T., Kotera, K., Tauchi, K., Tanaka, H., Ikada, K. & Igarashi, N.
Year:
1977
Bibliographic source:
Oyo Yakuri (Pharmacometrics) 13(5): 749-772

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Subacute toxicity of urea (28-days) by dermal exposure
GLP compliance:
no
Remarks:
: older, published study
Limit test:
no

Test material

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

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
No information available

Administration / exposure

Type of coverage:
not specified
Vehicle:
other: formulated as an ointment
Details on exposure:
Applied to back skin, an area of 20cm² in size
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No information available
Duration of treatment / exposure:
4 weeks
Frequency of treatment:
Daily
Doses / concentrations
Remarks:
Doses / Concentrations:
10%, 20%, 40%
Basis:
other: level of urea in ointment
No. of animals per sex per dose:
No information available
Control animals:
not specified
Details on study design:
Urea ointment was applied at three concentrations applied to 20cm² area of back skin for 4 weeks

Examinations

Observations and examinations performed and frequency:
Bodyweights were measured weekly, food and water consumption were measured at regular intervals. Clinical chemistry and haematology parameters were assessed in terminal blood samples; urinalysis parameters were also assessed.
Sacrifice and pathology:
Gross pathology and organ weights (liver, brain, heart, spleen, kidneys, pituitary, thyroid, thymus, adrenals, ovary, uterus, testes, prostate, seminal vesicles. Histopathology was also performed.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Dermal irritation:
not specified
Mortality:
no mortality observed
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:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
The authors note a number of effects in intermediate dose groups. They conclude that, compared to controls, there were no pathological changes in any organ, general symptoms, clinical chemistry, haematology or urinalysis parameters or pathological findings in treated groups.

Effect levels

Dose descriptor:
conc. level: 40% ointment
Sex:
male/female
Basis for effect level:
other: No dose-dependent toxicity observed
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

No dose-dependent toxicity was observed under the conditions of this study. Bodyweights, food and water consumption were unaffected by treatment. Clinical chemistry, haematology and urinalysis parameters were comparable in all groups. There was no effect of treatment on organ weights or pathology.

Applicant's summary and conclusion

Conclusions:
No effects of treatment were observed in this study.
Executive summary:

Urea (formulated as an ointment) was applied to the shorn dorsal skin of groups of male and female Wistar rats for 28 days. Bodyweights were measured; food and water consumption were assessed. Clinical chemistry, urinalysis and haematological parameters were investigated. At necropsy, organ weights were recorded; gross necropsy and histopathology were performed.

No dose-dependent toxicity was observed under the conditions of this study. Bodyweights, food and water consumption were unaffected by treatment. Clinical chemistry, haematology and urinalysis parameters were comparable in all groups. There was no effect of treatment on organ weights or pathology.