Apramycin

Overview

Synonyms
apramycin sulfate
CAS number
65710-07-8
JECFA number
75
Functional Class
Veterinary Drug
VETERINARY_DRUG

Evaluations

Evaluation year: 2011

ADI:
0–30 μg/kg bw

Comments:
The Committee considered that microbiological effects were more appropriate than toxicological effects for the establishment of an ADI for apramycin. Therefore, the Committee established an ADI of 0–30 μg/kg bw on the basis of the data for disruption of the colonization barrier. The ADI value was calculated using the following formula: Upper bound of the ADI (μg/kg bw) = (MICcalc (8.3 μg/ml) × Mass of colon content (220 g))/ (Bioavailable fraction of dose (1) × Body weight (60 kg)). Using the LOQs calculated by the Committee as residues for muscle, fat and liver, together with the proposed MRL for kidney, the TMDI would be 1400 μg/day and would not exceed the upper bound of the ADI. The sponsor is requested to provide improved validated analytical methods and residue depletion studies by the end of 2014.
MRL Comment:
Temporary MRLs of 5 mg/kg, cattle and chicken kidney
Intake:
TMDI: 1400 μg/day
Meeting:
75
Report: 
TRS 969/JECFA 75
Tox Monograph: 
Apramycin.pdf
Residues: 
FNP 12/12-JECFA 75

Toxicological study

Pivotal Study:
In vitro microbiological studies (Pridmore & Cheetham, 2011): The MIC of apramycin was determined against 100 bacterial strains, comprising 10 isolates from each of 10 groups of genera representing the normal intestinal microbiota: Bifidobacterium, Eubacterium, Clostridium, Bacteroides fragilis, other Bacteroides species (“non-fragilis group”), Fusobacterium, Peptostreptococcus,Lactobacillus, Enterococcus and Escherichia coli. All strains were sourced from faecal samples of healthy, unmedicated humans. The test system was standardized agar dilution MIC methodology using quality control strains.
Animal Specie:
Human gut flora
Effect:
Growth inhibition
Point of departure:
8.3 µg/ml (MICcalc/NOAEC)