Metenolone

Endpoint summary

Description of key information

There are no repeat-dose studies with ZK 5466. Read-across to results of studies with metenolone acetate (ZK 5469):
Subcutaneous, 2 weeks (Rat, non-GLP, dose: 0/ 4 mg, once daily): no effect
[Schering AG, 1960-11-29]
Subcutaneous, 26 weeks (Rat, non-GLP, doses: 0/ 0.33/ 3/ 10 mg/kg, every second day): NOEL < 0.33 mg/kg
[Schering AG, 1967-06-15]
Subcutaneous, 26 weeks (Dog-Beagle, non-GLP, doses: 0/ 6/ 20/ 40 mg/kg, every second day): NOEL: 6 mg/kg
[Schering AG, 1967-06-15]
Read-across to results of studies with ZK 5782 (metenolone enanthate):
Subcutaneous, 26 weeks (Rat, non-GLP, Doses: 0/ 1.5/ 15/ 50 mg/kg, once every second week; twice/week at high dose over last month): NOEL < 1.5 mg/kg
[Schering AG, 1962-02-07]
Subcutaneous, 26 weeks (Dog, non-GLP, Doses: 0/ 3/ 10 / 20 mg/kg, once every second week; twice/week at high dose over last month): NOEL = 20 mg/kg
[Schering AG, 1962-02-07]

Additional information

There are no repeat-dose toxicity studies conducted with ZK 5466 (metenolone). Results of studies with metenolone acetate (ZK 5469) or methenolone enanthate (ZK 5782) are regarded as representative as most likely ester cleavage occurs in vivo.

In rats, the once daily subcutaneous administration of 4 mg ZK 5469 to male and female animals over 2 weeks did not show any compound-related effects on body weight, clinical sings, organ weights and histopathological examination. [Schering AG, 1960-11-29]

After subcutaneous administration of ZK 5469 at doses of 0.33, 3 and 10 mg/kg every second day over 26 weeks, the following effects were seen: mortality in females (at 10 mg/kg) increased body weight at >= 3.0 mg/kg, inhibition of spermatogenesis in the testes (at >= 0.33 mg/kg) and of follicle maturation in the ovaries (at >= 3 mg/kg) as well as renal damage associated with increased concrements in urinary bladder in females only at >= 3 mg/kg. Mortality in females at the high dose (60% of animals) was associated with increased concrements in urinary bladder. All findings described are regarded as exaggerated pharmacodynamic effects of ZK 5469. Due to testes findings, the NOEL is < 0.33 mg/kg. [Schering AG, 1967-06-15]

In dogs after subcutaneous administration of ZK 5649 at doses of 6, 20 and 40 mg/kg every second day no substance-related findings besides increased body weight (>= 20 mg/kg) and inhibition of spermatogenesis (40 mg/kg) were observed. These effects are known pharmacodynamic effects of an anabolic steroids. No findings were described at the lowest dose tested (6.0 mg/kg). [Schering AG, 1967-06-15]

Compound-related findings in rats after subcutaneous administration of ZK 5782 at doses of 1.5, 15 and 50 mg/kg once every second week over 26 weeks are regarded as exaggerated pharmacodynamic effects and correspond to those described for ZK 5469. They include effects on body weight (increased in females at >= 15 mg/kg; reduced in males at >= 50 mg/kg), endocrine organs (reduced weights of adrenals at >= 15 mg/kg in females, reduced weight of ovaries and atrophy at >= 15 mg/kg; reduced weight of uterus at >= 1.5 mg/kg; reduced testes weights and atrophy at >= 1.5 mg/kg) and kidneys (interstitial nephritis in both sexes at 50 mg/kg). No other signs of organ toxicity and especially no signs of liver toxicity were observed. The NOEL is < 1.5 mg/kg due to effects on endocrine organs. [Schering AG, 1962-02-07]

The subcutaneous administration of ZK 5782 to male and female dogs over 26 weeks at doses of 3, 10 and 20 mg/kg once every second week was well tolerated without compound-related findings. The highest tested dose of 20 mg/kg corresponds to the NOEL. [Schering AG, 1962-02-07]

Therapeutic dosages for metenolone acetate in humans are 2 to 3 mg/day per os. Some known side effects of chronic treatment with anabolics are disturbances to the electrolyte metabolism and liver function.

Justification for classification or non-classification

Based on the results there is no classification required according to Directive 67/548/EEC and Regulation (EC) 1272/2008 (CLP).