17β-hydroxy-1α-methyl-5-αandrostan-3-one acetate

Repeated dose toxicity: oral

Administrative data

Endpoint:

chronic toxicity: oral

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 study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1967

Report date:

1967

Materials and methods

Test guideline

Qualifier:

no guideline available

GLP compliance:

no

Limit test:

no

Test material

Test material information

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): 1alpha-methylandrostane-17beta-ol-3-on

Test animals

Species:

dog

Strain:

Beagle

Sex:

male/female

Administration / exposure

Route of administration:

other: oral as tablets

Vehicle:

not specified

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

52 weeks

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0.6-3.6-10 mg/kg
Basis:
actual ingested

No. of animals per sex per dose:

3/sex

Control animals:

yes, plain diet

Results and discussion

Effect levels

Dose descriptor:

NOEL

Effect level:

< 0.6 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Substance specific effects on endocrine organs affected dose-dependently in both sexes (e.g. decreased weights of uterus (at 10 mg/kg), prostate (>= 0.6 mg/kg) and epidedymides, reduced testicular sperm count (at 10 mg/kg) and possibly lack of estral manifestation). Slight signs of liver toxicity were densification of cytoplasma and vacuolation of hepatocytes without corresponding finding in clinical pathology.

Applicant's summary and conclusion

Conclusions:

The NOEL is below the lowest tested dose of 0.6 mg/kg body weight after repeated dosing over 52 weeks.

Executive summary:

No acute toxicity studies were conducted with mesterolone acetate. Results of studies conducted with mesterolone (ZK 9226) are regarded as representative as most likely ester-cleavage occurs in vivo after administration.

The once daily oral administration of mesterolone (ZK 9226) to male and female Beagle dogs at doses of 0, 0.6, 3.6 and 10 mg/kg for 52 weeks was tolerated without clear signs of organ toxicity. Noteworthy findings were effects on endocrine organs affected dose-dependently in both sexes (e.g. decreased weights of uterus (at 10 mg/kg), prostate (>= 0.6 mg/kg) and epidedymides, reduced testicular sperm count (at 10 mg/kg) and possibly lack of estral manifestation). Slight signs of liver toxicity were densification of cytoplasma and vacuolation of hepatocytes without corresponding finding in clinical pathology. The NOEL is below the lowest tested dose of 0.6 mg/kg body weight after repeated dosing over 52 weeks.