Registration Dossier

Administrative data

Endpoint:
toxicity to reproduction: other studies
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: publication with well documented information

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1984
Report date:
1984

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
rats were laparotomized and various agents were injected into the uterine horns.
GLP compliance:
yes
Type of method:
in vivo

Test material

Constituent 1
Reference substance name:
Demeclocycline
EC Number:
204-834-8
EC Name:
Demeclocycline
Cas Number:
127-33-3
IUPAC Name:
7-chloro-4-(dimethylamino)-3,6,10,12,12a-pentahydroxy-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
Adult fenale Sprague-Dawley rats were housed in a standardized lighting environment (14 hr on; 10 hr off) and fed and watered ad libitum. Vaginal smears were observed to document cyclic activity and rats in the diestrus phase of the cycle were used for study.

Administration / exposure

Route of administration:
other: rats were laparotomized and various agents were injected into the uterine horns.
Vehicle:
unchanged (no vehicle)
Details on exposure:
Under ethyl ether anesthesia, rats were laparotomized and various agents were injected into the uterine horns. Injections were made in the right horn by grasping the cervical end of that horn with forceps and inserting a 21-gauge needle into the.lumen and a 0.2 ml volume of test substance was Injected via a tuberculin syringe. The horn was held with forceps for 30 seconds after injection to prevent reflux.
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
14days
Frequency of treatment:
one treatment
Duration of test:
14days
Doses / concentrations
Remarks:
Doses / Concentrations:
drugs and control(saline)
Basis:
actual ingested
10 mg
No. of animals per sex per dose:
5
Control animals:
other: saline(0.2 ml)
Details on study design:
The abdominal wall was sutured and the skin closed with wound clips. Two weeks later the animals were necropsied. The treated and non-treated uterine horns were fixed for histology and stained with hematoxylin and eosin.
Microscopic sections of the uterine horn were evaluated by an observer unaware of the treatment who scored the morphologic appearance as normal or abnormal. An abnormal section was one demonstrating epithelial or stromal necrosis, scarring, or inflammation.
Statistics:
no data

Results and discussion

Observed effects

Low doses (10 mg) of demeclocycline caused 80% incidence of necrosis, respectively. Furthermore, no dose of tetracycline or its analogues resulted in any mortality of the treated rats.

Applicant's summary and conclusion

Conclusions:
Based on the available data in this report, test material can cause uterine morphology changes but no mortality in the rats.
Executive summary:

This study was conducted to screen other drugs for their uterine morphology in the rats. The drugs tested include quinacrine-like compounds, and tetracycline and its analogues(exp. test article) which are known sclerosing agents. Tetracycline and its analogues produced quinacrine-like morphologic changes in the rat and showed no toxicity for the dose tested. It was indicated that no mortality but uterine necrosis was observed with test material.