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Toxicological information

Repeated dose toxicity: other routes

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Administrative data

Endpoint:
sub-chronic toxicity: other route
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
Dec 1972 to May 1973
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: well reported study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1973
Report date:
1973

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Rats (15/sex/group) reveived once every 21 days single subcutaneous injections of testosterone enanthate over a period of 26 week at the doses of 0, 2, 6 and 20 mg/kg.
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Reference substance name:
testosterone enanthate
IUPAC Name:
testosterone enanthate
Details on test material:
- Name of test material (as cited in study report): testosterone enanthate (ZK 5137)

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female

Administration / exposure

Route of administration:
subcutaneous
Vehicle:
other: sesame oil
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
once every 21 days for 26 weeks
Frequency of treatment:
once every 21 days
Doses / concentrations
Remarks:
Doses / Concentrations:
2, 6 and 20 mg/kg
No. of animals per sex per dose:
15/sex/group
Control animals:
yes, concurrent vehicle

Results and discussion

Effect levels

Dose descriptor:
NOAEL
Effect level:
2 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: overall effects

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Body weight gain was increased in females from the mid dose onwards, whereas high dose males showed a decreased weight gain compared to controls. A depression of total serum protein levels was found after 20 mg/kg in male rats and from 6 mg/kg onwards in female rats. Albumin and alpha-1 globulin levels were decreased in females from 6 mg/kg upwards. Testicular weights were decreased in all treatment groups without histological changes. In female rats liver weight increased in the high dose group, again without a histological correlate. Weight decrease of the ovaries, the uterus and the adrenals was noted in female rats from 6 mg/kg, onwards. An increased number of atretic follicles and absence of mature corpora lutea in the ovaries were seen in all animals of the high dose group and only one animal at the mid dose-level. This finding was associated in a number of animals with a minimal endometrial hyperplasia in the uterus. Minimal mammary hyperplasia was recorded either from 6 mg/kg in males or at 20 mg/kg in females.

Applicant's summary and conclusion

Conclusions:
Test substance NOAEL, in rats, is 2 mg/kg based on impact on sexual organs.
Executive summary:

There is no repeated dose toxicity studies on testosterone available. Results of a study conducted with an ester of testosterone (testosterone enanthate, ZK 5137) is reported as ester cleavage occurs in vivo after administration.

15 male and 15 female rats per group received testosterone enanthate in doses of 2, 6 and 20 mg/kg once every 21 days over a period of 26 weeks. Body weight gain was increased in females from the mid dose onwards, whereas high dose males showed a decreased weight gain compared to controls. A depression of total serum protein levels was found after 20 mg/kg in male rats and from 6 mg/kg onwards in female rats. Albumin and alpha-1 globulin levels were decreased in females from 6 mg/kg upwards. Testicular weights were decreased in all treatment groups without histological changes and is therefore not considered as adverse effect. In female rats liver weight increased in the high dose group, again without a histological correlate. Weight decrease of the ovaries, the uterus and the adrenals was noted in female rats from 6 mg/kg, onwards. An increased number of atretic follicles and absence of mature corpora lutea in the ovaries were seen in all animals of the high dose group and only one animal at the mid dose-level. This finding was associated in a number of animals with a minimal endometrial hyperplasia in the uterus. Minimal mammary hyperplasia was recorded either from 6 mg/kg in males or at 20 mg/kg in females.