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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
10. Nov to 9. Dec. 1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline GPL study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report date:
1996

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
Deviations:
no
GLP compliance:
yes
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Androst-4-ene-3,17-dione
EC Number:
200-554-5
EC Name:
Androst-4-ene-3,17-dione
Cas Number:
63-05-8
Molecular formula:
C19H26O2
IUPAC Name:
androst-4-ene-3,17-dione

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
physiological saline
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
28/29 days
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0-15-50-150 mg/kg bw per day
Basis:
actual ingested
No. of animals per sex per dose:
6/sex/dose
Control animals:
yes, concurrent vehicle

Results and discussion

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Dose-dependently increasing effects such as increased body weight (>=15 mg/kg bw/day, F), atrophy of uterus and cervix (>= 15 mg/kg bw/day, F), pituitary gland (>=50 mg/kg bw/day , F) and adrenals (150 mg/kg bw/day, F), as well as increased erythrocytes and hemoglobin (>= 15 mg/kg bw/day, F). Increased liver weights (150 mg/kg bw/day, M+F) and increases of liver ALP and GLP transaminases (150 mg/kg bw/day, M+F).

Applicant's summary and conclusion

Conclusions:
A No Observed Effects Level could not be established. The LOEL is 15 mg/kg bw/day, based on increased bodyweight and atrophy to uterus and cervix. These effects are not suitable to lead to repeat dose hazard classification, according to CLP or DSD.
Executive summary:

There are no available repeat dose toxicity studies on testosterone. Results of a study conducted with a structurally similar compound (androstenedione, ZK5155) are reported for read-across

The once daily oral administration of ZK 5155 to male and female rats over 4 weeks at doses of 0, 15, 50 and 150 mg/kg bw/day led to dose-dependently increasing effects such as increased body weight (>=15 mg/kg bw/day, F), atrophy of uterus and cervix (>= 15 mg/kg bw/day, F), pituitary gland (>=50 mg/kg bw/day, F) and adrenals (150 mg/kg bw/day, F), as well as increased erythrocytes and hemoglobin (>= 15 mg/kg bw/day, F). These effects are regarded to represent endocrine effects typical for a steroid hormone. Increased liver weights (150 mg/kg bw/day, M+F) and increases of liver transaminases (150 mg/kg bw/day, M+F) represent beginning organ toxicity. A no-observed-effect-level (NOEL) was not established. Females were more sensitive than males.