Amoxicillin

Overview

Chemical Names
amoxicillin trihydrate; amoxicillin sodium salt
CAS number
61336-70-7
JECFA number
85
Functional Class
Veterinary Drug

Evaluations

Evaluation year: 2017

ADI:
0-0.002 mg/kg bw

Comments:
Microbiological ADI based on the effects of amoxicillin on the intestinal microbiota. ARfD: 0.005 mg/kg, based on microbiological effects and using the newly adopted colon volume of 500 mL
MRL Comment:
50 microg/kg in finfish fillet and muscle
Intake:
GECDE 0.14μg/kg bw per day, which represents 7% of the upper bound of the mADI. GEADE 1.4 μg/kg bw for gal population and 1.6 μg/kg bw for children (Respectively 28% and 31% of the microbiological ARfD).
Report: 
JECFA 85 report

Toxicological study

Animal Specie:
Human
Effect:
Effects of amoxicillin on the intestinal microbiota

Evaluation year: 2011

ADI:
0–0.7 μg/kg bw
Comments:
Hypersensitivity was considered to be the toxicological effect of concern. Available limited evidence indicates that, compared with benzylpenicillin and possibly other penicillins, amoxicillin is less chemically reactive with proteins to form haptens. The Committee was unable to identify any cases of allergy following oral exposure to food residues of amoxicillin. The Committee concluded that the value of 30 μg/person previously established by the 36th meeting to protect against allergic reactions from residues of penicillins would be unnecessarily conservative. A microbiological ADI of 0–42 μg/person (0–0.7 μg/kg bw) for adverse effects on gut flora would be sufficient to ensure that allergic reactions would be unlikely to occur. The ADI value was calculated using the following formula: Upper bound of the ADI (μg/kg bw) = (MICcalc (0.10 μg/ml) × Mass of colon content (220 g))/ (Bioavailable fraction of dose (0.566) × Body weight (60 kg)). Using a model diet, the TMDI is 31 μg/p/day (74% upper bound ADI) for summed intake at the MRLs for milk & meat.
MRL Comment:
MRLs for amoxicillin (as parent compound), cattle, sheep and pig tissues: 50 μg/kg; cattle & sheep milk: 4 μg/kg
Intake:
TMDI: 31 μ g/person/day
Meeting:
75
Report: 
TRS 969 JECFA 75
Tox Monograph: 
Amoxicillin.pdf
Residues: 
FNP12/12-JECFA 75

Toxicological study

Pivotal Study:
In vitro microbiological growth inhibition study (Sutter & Finegold, 1976): MICcalc value based on MIC50 values for Escherichia coli (MIC50 = 5 µg/ml), Bifidobacterium (MIC50 = 0.06 µg/ml), Clostridium (MIC50 = 0.1 µg/ml), Bacteroides (MIC50 = 0.5 µg/ml), Lactobacillus (MIC50 = 0.25 µg/ml), Fusobacterium (MIC50 = 0.1 µg/ml), Eubacterium (MIC50 = 0.1 µg/ml) and Peptostreptococcus (MIC50 = 0.1 µg/ml).
Animal Specie:
Human gut flora
Effect:
Growth inhibition
Point of departure:
0.10 µg/ml (MICcalc, NOAEC))