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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
other information
Study period:
25. Jun 1969 to 15. Jul 1969
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: well reported study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1970
Report Date:
1970

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
After appropriate acclimation period (7 days) single dose of norethisterone enanthate was applied subcutaneously to female rats on day 6 p.c. (12/group) in the doses of 0, 6 and 60 mg/kg. All animals were housed under standard conditions and observed daily for clinical signs. On day 19 of pregnancy, fetuses were removed from 10 dams via section. On day 21 of pregnancy further 6 dams were sacrificed via section and fetuses removed. All animals were examined macroscopically.
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): norethisterone enanthate (ZK5410)

Test animals

Species:
rat
Strain:
Sprague-Dawley

Administration / exposure

Route of administration:
subcutaneous
Vehicle:
castor oil
Analytical verification of doses or concentrations:
no
Details on mating procedure:
- Impregnation procedure: cohoused
- M/F ratio per cage: 1/4
- Length of cohabitation: no data
- Proof of pregnancy: vaginal plug or sperm in vaginal smear referred to as day 0 of pregnancy
Duration of treatment / exposure:
1 day
Frequency of treatment:
once
Duration of test:
until day 21 of pregancy
No. of animals per sex per dose:
12 females/dose
Control animals:
yes, concurrent vehicle

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

Dose descriptor:
NOEL
Effect level:
>= 6 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

Body weight gain of high dose females was reduced

Applicant's summary and conclusion

Conclusions:
no effects on fetuses were observed
Executive summary:

No developmental toxicity studies were conducted with ZK 5378 (norethiosterone). Results of studies conducted with an ester of norethisterone (norethisterone enanthate, ZK 5410) are regarded as representative as most likely ester cleavage occurs in vivo after administration.

The single subcutaneous administration of norethisterone enanthate on day 6 p.c. to female rats (12/group) in the doses of 0, 6 and 60 mg/kg was tolerated well. Only the body weight gain of high dose females was reduced. The NOEL for maternal toxicity was 6 mg/kg body weight.