PROVAMYCIN
Overview
Chemical Names
SPIRAMYCIN
Synonyms
FOROMACIDIN; SEQUAMYCIN; SELECTOMYCIN; ROVAMYCIN; PROVAMYCIN
CAS number
8025-81-8
Functional Class
Veterinary Drug
ANTIMICROBIAL_AGENT
ANTIMICROBIAL_AGENT
Evaluations
Evaluation year: 1998
ADI:0-0.05 mg/kg bw
ADI:
0-0.05 mg/kg bw
Comments:
Spiramycin had previously been evaluated at the 12th & 38th Committee meetings. Based on the estimated concentration with no effect on the human gut flora, a temporary ADI of 0-5 µg/kg bw was established at the 38th meeting, with the requirement of additional in vivo studies on the effect of spiramycin on the human intestinal flora. In view of the additional reassurance provided by the new data, and as these studies covered a wide range of organisms, the Committee reconsidered the magnitude of the safety factor and concluded that a safety factor of 1 instead of 10, was appropriate. The other parameters used in the previous evaluation provide a conservative estimate. As a result the Committee established an ADI of 0-50 µg/kg bw, using the formula: ADI (µg/kg bw) = (1 µg/ml (concentration without effect on gut flora) x 150 g (fecal bolus))/(0.05 (bioavailable fraction) x 1 (safety factor) x 60 kg (adult weight)) = 50 µg/kg bw.
MRL Comment:
MRLs (in mg/kg tissue, mg/l milk): Muscle (cattle, chickens and pigs): 0.2; Liver (cattle, chickens and pigs): 0.6; Kidney (cattle and pigs): 0.3; Kidney (chickens): 0.8; Fat (cattle, pigs and chickens): 0.3; Milk (cattle): 0.2. For cattle and chickens, MRLs are expressed as the sum of the concentrations of spiramycin and neospiramycin. MRLs for pigs are based on total antimicrobially active residues and expressed as spiramycin equivalents. Except for milk, all MRLs were established at the 47th meeting.
MRL Code:
MRL
Intake:
TMDI 0.44 mg/p/d spiramycin equivalents
Meeting:
48
Report:
Tox Monograph:
Residues:
Toxicological study
Pivotal Study:
In vitro microbiological studies with human GI-flora (Roques, 1989, as cited in Rico, 1990): MICs varied from 0.25-2 µg/ml in pure culture at 106 bacteria/ml. At 109 bacteria/ml the observed MIC values for the strains used varied from 2 to >128 µg/ml. In mixed culture the MIC values were 16 µg/ml at 106 bacteria/ml and >128 µg/ml at 109 bacteria/ml. A modal MIC of 0.5 µg/ml was estimated. The Committee divided this value by a factor of 10 in order to adequately cover the range of MICs for sensitive bacteria. The resulting value was multiplied by 20 in view of the uncertainties in the extrapolation of data on the inhibition of bacterial growth from in vitro conditions to the conditions of growth in the gut. As a result of such extrapolation, a concentration without effect on the human intestinal flora of 0.5 x 20/10 = 1 µg/ml (equivalent to 1 µg/g) was estimated.
Animal Specie:
Human gut flora
Effect:
Growth inhibition
Point of departure:
1 µg/ml (concentration without effect on gut flora)
Previous Years:
1996, TRS 876-JECFA 47/27, FNP 41/9-JECFA 47/77, FAS 34-JECFA 43/143 (1994). 0-0.05 (1994). MRLs: MUSCLE (CATTLE, PIGS AND CHICKENS): 0.2; LIVER (CATTLE, PIGS AND CHICKENS): 0.6; KIDNEY (CATTLE AND PIGS): 0.3; KIDNEY (CHICKENS): 0.8; FAT (CATTLE, PIGS AN
1996, TRS 876-JECFA 47/27, FNP 41/9-JECFA 47/77, FAS 34-JECFA 43/143 (1994). 0-0.05 (1994). MRLs: MUSCLE (CATTLE, PIGS AND CHICKENS): 0.2; LIVER (CATTLE, PIGS AND CHICKENS): 0.6; KIDNEY (CATTLE AND PIGS): 0.3; KIDNEY (CHICKENS): 0.8; FAT (CATTLE, PIGS AN