Registration Dossier

Administrative data

Endpoint:
chronic toxicity: other route
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: well reported study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report Date:
1978

Materials and methods

Test guideline
Qualifier:
no guideline available
Deviations:
not applicable
GLP compliance:
no
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): estradiol

Test animals

Species:
dog
Strain:
Beagle
Sex:
female

Administration / exposure

Route of administration:
intramuscular
Vehicle:
castor oil
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
52 or 66 weeks
Frequency of treatment:
every 3rd daily (day 1, 4, 7, 10, ...) or weekly
Doses / concentrations
Remarks:
Doses / Concentrations:
1.28 mg/kg every third day or once weekly
No. of animals per sex per dose:
6/group
Control animals:
yes, concurrent vehicle

Results and discussion

Effect levels

Effect level:
< 1.28 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Alopecia, alteration of mammary gland, vaginal discharge, anemia, transient leucocytosis, thrombocytopenia, decrease of reticulocytes, enhanced erytrocyte sedimetation rate, increased fibrinogen and coagulation time, increase in glucose and cholesterol..

Parenchymal and follicular atrophy of ovaries, papillary hyperplasia in ovaries, intestinal fibrosis of endometrium, atrophy and cystic dilatation of endometrial gland, hypertrophy and fibrosis of myometrium, increase in thickness of vaginal epithelium, edema and thickening of vulva propria and parenchymal proliferation of mammary gland, cortical nodular hyperplasia and marked depetion of lipid content of adrenal gland.

Applicant's summary and conclusion

Conclusions:
Classification is not required.
Executive summary:

The administration of 1.28 mg/kg twice or once a week in female dogs over a period of 52 to 66 weeks did not produce any morphological features that indicate any neoplastic or anaplastic processes. Benign proliferative leasions of mesothelium lining of genital organs together with clinical, biochemical and haematological changes known to be related to estrogen effects were observed.