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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
fertility, other
Remarks:
based on test type (migrated information)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
other information
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: well reported pre-guideline 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
Limit test:
no

Test material

Constituent 1
Reference substance name:
Automatically generated during migration to IUCLID 6, no data available
IUPAC Name:
Automatically generated during migration to IUCLID 6, no data available
Details on test material:
- Name of test material (as cited in study report): Gestonorone-caproate

Test animals

Species:
rat
Strain:
not specified
Sex:
male

Administration / exposure

Route of administration:
subcutaneous
Vehicle:
castor oil
Details on mating procedure:
2 weeks mating period
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
10 weeks pre-mating and 2 weeks during mating period with untreated females
Frequency of treatment:
twice weekly
Details on study schedule:
Males were treated 10 weeks pre-mating and 2 weeks during mating period with untreated females until successful copulation. The efefcts of the administered compound on the fertility and the development of the foetuses were studied.. Caesarian was derived on day 21 of pregnancy
Doses / concentrations
Remarks:
Doses / Concentrations:
2, 20 and 200 mg/kg
Basis:
no data
No. of animals per sex per dose:
22/group
Control animals:
yes, concurrent vehicle

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

Dose descriptor:
NOEL
Effect level:
<= 2 mg/kg diet
Sex:
male

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

Dose-dependently decreased male fertility was seen at the dose of 20 mg/kg and higher, including decreased weights of male reproductive organs. In addition, increased numbers of total resorptions were seen at 20 mg/kg and higher. The slight increase of the resorption rate after 20 mg/kg depends mainly on one dam with 8 resorption sites, whereas all other animals showed no elevation of the total number of resorptions.

Applicant's summary and conclusion

Conclusions:
According to the Directive 67/548 EEC, following classification for gestonoron capronate is proposed
Category 1; R60 - May impair fertility.
Executive summary:

No reproductive toxicity studies were conducted with ZK 5686 (gestonorone). Results of studies conducted with an ester of gestonorone (ZK 5623, gestonorone caproate) are regarded as representative as most likely ester cleavage occurs in vivo after administration.

Effects of ZK 5623 on male fertility was assessed in rats with subcutaneous administration (twice weekly, ten weeks premating and up to two weeks mating) of doses of 2, 20, and 200 mg/kg. Dose-dependently decreased male fertility was seen at the dose of 20 mg/kg and higher, including decreased weights of male reproductive organs. In addition, increased numbers of total resorptions were seen at 20 mg/kg and higher.