ERYTHROMYCIN

Overview

Chemical Names
ERYTHROMYCIN A: 6-(4-DIMETHYLAMINO-3-HYDROXY-6-METHYL-TETRAHYDROPYRAN-2-YL)OXY-14-ETHYL-7,12,13-TRIHYDROXY-4-(5-HYDROXY-4-METHOXY-4,6-DIMETHYLTETRAHYDROPYRAN-2-YL)OXY-3,5,7,9,11,13-HEXAMETHYL-1-OXACYCLOTETRADECANE-2,10-DIONE)
CAS number
114-07-8
Functional Class
Veterinary Drug
ANTIMICROBIAL_AGENT

Evaluations

Evaluation year: 2006

ADI:
0-0.7 µg/kg bw

Comments:
The Committee considered that the microbiological effects of erythromycin were more relevant than the toxicological effects for risk assessment and established an ADI of 0–0.7 µg/kg bw, on the basis of the MIC50 of 0.1 µg/g for Bifidobacterium using the following formula: Upper limit of ADI (µg/kg bw) = (0.1 µg/g (MIC50) x 220 g (mass of colon contents))/(0.5 (bioavailable fraction) x 1 (safety factor) x 60 kg (adult bodyweight)). The Committee then used a margin-of-exposure approach between the ADI and LOEL values to compare the microbiological ADI with potentially relevant toxicological endpoints. An MOE of 300,000 was calculated between the LOEL for liver granulomas & bone marrow reticular cell hyperplasia in female rats in a 2-year dietary study conducted with erythromycin stearate. An MOE of 10,000 was also calculated between the microbiological ADI and the therapeutic dose of 8 mg/kg bw/d associated with development of infantile pyloric stenosis in humans.
MRL Comment:
MRLs: FAT,KIDNEY, LIVER AND MUSCLE (CHICKEN AND TURKEY): 100 µg/kg; EGGS (CHICKEN): 50 µg/kgThe MRL for fat includes skin + fat where appropriate.
MRL Code:
N
Intake:
TMDI using a model diet: 55mg/day (130% of the ADI); EDI for erythromycin at median residue concentrations: 27.5mg/day (65% of the ADI)
Meeting:
66
Report: 
TRS 939-JECFA 66/33
Tox Monograph: 
FAS 57-JECFA66/31
Residues: 
FAO JECFA MONOGRAPHS 2-JECFA 66/29

Toxicological study

Pivotal Study:
Microbiological study on gut flora in vitro (Delgado et al., 2005)
Animal Specie:
Human gut flora
Effect:
Growth inhibition
Point of departure:
0.1 µg/g (MIC50)
Previous Years:
1968, NMRS 45/TRS 430-JECFA 12/18, FAS 69.34/NMRS 45A-JECFA 12/9, NMRS 45/TRS 430-JECFA 12/18. NO ADI ALLOCATED. ACCEPTABLE LEVELS OF RESIDUES: MILK: 0-0.04 ppm; MEAT: 0-0.3 ppm; EGGS: 0-0.3 ppm
1968, NMRS 45/TRS 430-JECFA 12/18, FAS 69.34/NMRS 45A-JECFA 12/9, NMRS 45/TRS 430-JECFA 12/18. NO ADI ALLOCATED. ACCEPTABLE LEVELS OF RESIDUES: MILK: 0-0.04 ppm; MEAT: 0-0.3 ppm; EGGS: 0-0.3 ppm