Registration Dossier

Administrative data

Endpoint:
toxicity to reproduction: other studies
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
other information
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
GLP compliance:
no
Type of method:
in vivo

Test material

Constituent 1
Chemical structure
Reference substance name:
Gestonorone caproate
EC Number:
215-010-2
EC Name:
Gestonorone caproate
Cas Number:
1253-28-7
Molecular formula:
C26H38O4
IUPAC Name:
17-acetyl-3-oxoestr-4-en-17-yl hexanoate

Test animals

Species:
rat
Strain:
not specified
Sex:
female

Administration / exposure

Route of administration:
subcutaneous
Vehicle:
castor oil
Remarks:
with benzyl benzoat
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Days 17 and 20 p.c. and during the weaning period (Days 1, 4, 7, 10, 13, 16 and 19 p.p.)
Frequency of treatment:
daily
Duration of test:
no data
Doses / concentrations
Remarks:
Doses / Concentrations:
2 - 20 - 200 mg/kg
Basis:
no data
No. of animals per sex per dose:
20, 24 or 22 pregnant rats/group
(18 control rats)
Control animals:
yes, concurrent vehicle

Results and discussion

Effect levels

Dose descriptor:
NOEL
Effect level:
20 mg/kg bw/day
Basis for effect level:
other: prevent spontaneous delivery

Observed effects

At the high dose, spontenous delivery was prevented by treatment in nearly all animals. Only dead fetuses were detected in high dose animals sacrificed on Day 24 p.c. No effects of gestonorone capraote were seen on any of the other parameters assessed in this study at the two lower doses tested.

Applicant's summary and conclusion

Conclusions:
Gestonorone caproate did prevent spontaneous delivery
Executive summary:

No reproductive toxicity studies were conducted with ZK 5624 (gestonorone acetate). Results of studies conducted with a different ester of gestonorone (ZK 5623, gestonorone caproate) are regarded as representative as most likely ester cleavage occurs in vivo after administration.

The effect of gestonorone caproate (ZK 5623) on peri- and postnatal development (effects on dams, reared pups of F1 generation and F2 fetuses) was assessed by subcutaneous treatment of rats (P generation) at end of pregnancy (Days 17 and 20 p.c.) and during the weaning period (Days 1, 4, 7, 10, 13, 16 and 19 p.p.) with doses of 2, 20 and 200 mg/kg. At the high dose, spontenous delivery was prevented by treatment in nearly all animals. Only dead fetuses were detected in high dose animals sacrificed on Day 24 p.c. No effects of ZK 5623 were seen on any of the other parameters assessed in this study at the two lower doses tested.