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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Developmental toxicity / teratogenicity

Currently viewing:

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
other information
Study period:
02/1970 - 07/1970
Reliability:
2 (reliable with restrictions)
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
Principles of method if other than guideline:
After appropriate acclimation period female rabbits were mated with male animals. 20 Pregnant mice per dose group were orally administered norethisterone acetate at doses of 12 and 48 mg/kg bw/day during GD 7-13, in each group 5/20 dams were allowed to deliver spontaneously. The other dams were sacrificed on day 18 of gestation, fetuses were removed from dams via section. All animals were examined macroscopically.
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Norethisterone acetate
EC Number:
200-132-0
EC Name:
Norethisterone acetate
Cas Number:
51-98-9
Molecular formula:
C22H28O3
IUPAC Name:
17-ethynyl-3-oxoestr-4-en-17-yl acetate

Test animals

Species:
mouse
Strain:
ICR

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
other: tragacant 1%
Duration of treatment / exposure:
day 7- 13 of gestation
Frequency of treatment:
daily
Doses / concentrationsopen allclose all
Dose / conc.:
12 mg/kg bw/day (actual dose received)
Dose / conc.:
48 mg/kg bw/day (actual dose received)
No. of animals per sex per dose:
20 (15 caesarean section, 5 spontaneous delivery)
Control animals:
yes, concurrent vehicle

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
>= 48 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
other: no effects observed

Maternal abnormalities

Abnormalities:
no effects observed

Results (fetuses)

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
12 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
reduction in number of live offspring
changes in postnatal survival

Fetal abnormalities

Abnormalities:
no effects observed

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Executive summary:

No prenatal developmental toxicity studies were conducted with ZK 5378 (norethisterone). Results of studies conducted with an ester of norethisterone (norethisterone acetate, ZK 5422) are regarded as representative as most likely ester cleavage occurs in vivo after administration.


In a test where pregnant mice of Day 7-13 received doses of 48 and 12 mg/kg p.o., the number of perinatal death increased at a dose of 48 mg/kg. No teratogenic effects were observed at both doses.