Estrone

Repeated dose toxicity: other routes

Administrative data

Endpoint:

chronic toxicity: other route

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1978

Report date:

1978

Materials and methods

Test guideline

Qualifier:

no guideline available

GLP compliance:

no

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Estradiol

EC Number:

200-023-8

EC Name:

Estradiol

Cas Number:

50-28-2

Molecular formula:

C18H24O2

IUPAC Name:

estra-1,3,5(10)-triene-3,17-diol

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

Basis for effect level:

other: ovarian carcinoma

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.