TRENBOLONE ACETATE
Overview
Chemical Names
17beta-ACETOXY-3-OXOESTRA-4,9,11-TRIENE; 17beta-ACETOXYESTRA-4,9,11-TRIEN-3-ONE
Synonyms
TRENBOLONE; TRIENBOLONE; TRIENOLONE
CAS number
10161-34-9
Functional Class
Veterinary Drug
GROWTH_PROMOTER
GROWTH_PROMOTER
Evaluations
Evaluation year: 1989
ADI:0-0.02 µg/kg bw
ADI:
0-0.02 µg/kg bw
Comments:
In accordance with the decisions taken at the 32nd meeting, it was decided to base the evaluation of TBA and its metabolites on their no-hormonal-effect level. The results of three hormonal studies in pigs carried out with TBA, alpha-TBOH or ß-TBOH were re-evaluated. The previous no-hormonal-effect levels of 10 µg/kg bw/day for ß-TBOH and 100 µg/kg bw/day for alpha-TBOH, determined in castrated pigs, were confirmed. In a 14-week study in male and female pigs given TBA in capsules, the LOEL of 0.1 ppm (equal to 2 to 3 µg/kg bw/d for changes in serum testosterone and estradiol concentrations and testes weight in male pigs was considered the appropriate point of departure. An ADI of 0-0.02 µg/kg bw for TBA was calculated based on theis LOEL and a safety factor of 100. This LOEL for hormonal effects for TBA was supported by the no-hormonal-effect level of 2 µg/kg bw/day for ß-TBOH in monkeys.
MRL Comment:
MRLs (in mg/kg): Muscle: 0.002 (as beta-trenbolone); Liver: 0.01 (as alpha-trenbolone)
MRL Code:
MRL
Intake:
TMDI: 1.3 µg/p/d, if all bioavailable residues in tissue are beta-TBOH; 0.7 µg/p/d, if all bioavailable residues in liver & kidney were alpha-TBOH & all residues in muscle were beta-TBOH
Meeting:
34
Report:
Tox Monograph:
Residues:
Toxicological study
Pivotal Study:
14-week pig study (Ross et al., 1980): Large white hybrid domestic pigs (Sus scrofa, 26 weeks old, 4/sex) were fed diets containing 0, 0.1, 2.0 or 20 ppm (0, 2-3, 40-100 or 400-600 µg/kg bw/d) TBA for 14 weeks (spanning the period of puberty). Significant dose-related hematological effects were found (at week 12) in females receiving 2.0 or 20 ppm TBA. Biochemistry effects noted: increased cholesterol in both sexes at 2.0 and 20 ppm, increased urea and ASAT at 20 ppm, decreased tesosterone & estradiol in males at 2 and 20 ppm, and decreased progesterone in 2 & 20 ppm females. Seminal vesicle and pituitary weights were increased at 20 ppm. At 2 and 20 ppm TBA, dose-related changes were observed in liver and kidney weight (increase), uterus weight (decrease) and testes weight (decrease). A marginal effect on testicular weight was observed at the lowest dose of 0.1 ppm. Dose-related enlargement of hepatocytes, with associated "ground glass" appearance of the cytoplasm), testes (interstitial cell atrophy), ovaries (suppressed or abnormal cyclical activity, characterized by the absence of maturing follicles and/or mature or early regressing corpora lutea) and in the uterus (absence of glandular development of the endometrium) at 2 and 20 ppm TBA. A marginal no-hormonal effect level of 0.1 ppm TBA (equal to a range of 2-3 µg/kg bw/day) is indicated.
Animal Specie:
Pigs
Effect:
Changes in serum testosterone and estradiol and testes weight
LOEL:
2 µg/kg bw/d
Point of departure:
2 µg/kg bw/d
Previous Years:
1987, TRS 763-JECFA 32/23, FNP 41-JECFA 32/30, FAS 23-JECFA 32/73. 0-0.00001 (TEMPORARY). ACCEPTABLE RESIDUE LEVELS: 0.0014 (BOVINE TISSUE) FOR beta-TRENBOLONE (TEMPORARY); 0.014 (BOVINE LIVER AND KIDNEY) FOR alpha-TRENBOLONE (TEMPORARY). TE. TMRL
1983,
1987, TRS 763-JECFA 32/23, FNP 41-JECFA 32/30, FAS 23-JECFA 32/73. 0-0.00001 (TEMPORARY). ACCEPTABLE RESIDUE LEVELS: 0.0014 (BOVINE TISSUE) FOR beta-TRENBOLONE (TEMPORARY); 0.014 (BOVINE LIVER AND KIDNEY) FOR alpha-TRENBOLONE (TEMPORARY). TE. TMRL
1983,