RACTOPAMINE HYDROCHLORIDE
Overview
Chemical Names
dl-p-alpha-[[[HYDROXYPHENYL-1-METHYLPROPYL]AMINO]METHYL]BENZENE METHANOL HYDROCHLORIDE (TWO DIASTEREOMERIC FORMS: RS,SR AND RR,SS)
Functional Class
Veterinary Drug
ADRENOCEPTOR_AGONIST
GROWTH_PROMOTER
ADRENOCEPTOR_AGONIST
GROWTH_PROMOTER
Evaluations
Evaluation year: 2006
ADI:0-1 µg/kg bw
ADI:
0-1 µg/kg bw
Comments:
The 62nd Committee concluded that acute cardiac responses in humans were the most appropriate endpoints for the calculation of an ADI. A combined NOEL of 67 µg/kg was determined on the basis of changes in electromechanical systole, left ventricular ejection time, and maximum velocity of circumferential fibre shortening. A safety factor of 10 was used to account for individual variability and an additional safety factor of 5 was used to protect sensitive individuals and in view of the small sample size in the study, thus resulting in a combined safety factor of 50. This approach provides a margin of safety of at least 20 000 with respect to the formation of leiomyomas in mice and rats. The Committee established an ADI for ractopamine of 0–1 µg/kg/d, based on the NOEL of 67 µg/kg and a safety factor of 50, rounded to one significant figure.
MRL Comment:
MRLs (EXPRESSED AS RACTOPAMINE): MUSCLE AND FAT (CATTLE AND PIGS): 10 µg/kg; LIVER (CATTLE AND PIGS): 40 µg/kg; KIDNEY (CATTLE AND PIGS): 90 µg/kg.
Intake:
50 µg/p/d TMDI (84% of ADI), EDI using median residue values: 9 µg/p/d (15% of ADI)
Meeting:
66
Report:
Tox Monograph:
Residues:
Toxicological study
Pivotal Study:
Single-blind, placebo-controlled, ascending single-dose protocol (Hunt, 1994; Food & Drug Administration, 1999): Six healthy males (67.8–79.6 kg; mean, 75.5 kg) were given oral placebo plus five oral doses of 5, 10, 15, 25, and 40 mg of ractopamine, with a washout period of 48h between doses. On a body-weight basis, the doses ranged from 0.063 to 0.590 mg/kg bw. Using
standard and echocardiographic methods, measurements for 14 cardiovascular variables were obtained at 9 hourly time-points in each subject. Dose-dependent changes of cardiac variables appeared within the first hour after administration of ractopamine and gradually returned to baseline values before treatment. At a dose of 5 mg, there was apparently no cardiovascular response, and at 10 mg only minor effects were reported. At 15, 25, and 40 mg, the heart rate was elevated, cardiac output increased, the electromechanical systole was shortened, and systolic blood pressure increased. The Committee considered the NOEL of the study to be 5 mg, or 67 µg/kg.
Animal Specie:
Human
Effect:
Changes in cardiovascular function variables
NOEL:
67 µg/kg bw
Point of departure:
67 µg/kg
Previous Years:
2004, TRS 925-JECFA 62/37, FNP 41/16-JECFA 62/75, FAS 53-JECFA 62/119. 0-1 µg/kg bw. MRLs (EXPRESSED AS RACTOPAMINE): MUSCLE AND FAT (CATTLE AND PIGS): 10 µg/kg; LIVER (CATTLE AND PIGS): 40 µg/kg; KIDNEY (CATTLE AND PIGS): 90 µg/kg.
1992, TRS 832-JECFA 4
2004, TRS 925-JECFA 62/37, FNP 41/16-JECFA 62/75, FAS 53-JECFA 62/119. 0-1 µg/kg bw. MRLs (EXPRESSED AS RACTOPAMINE): MUSCLE AND FAT (CATTLE AND PIGS): 10 µg/kg; LIVER (CATTLE AND PIGS): 40 µg/kg; KIDNEY (CATTLE AND PIGS): 90 µg/kg.
1992, TRS 832-JECFA 4