NEOMYCIN

Overview

Chemical Names
D-STREPTAMINE, O-2,6-DIAMINO-2,6-DIDEOXY-alpha-D-GLUCOPYRANOSYL-(1–>4)-O-[O-2,6- DIAMINO-2,6-DIDEOXY-beta-L-IDOPYRANOSYL-(1–>3)-beta-D-RIBOFURANOSYL-(1–>5)]-2- DEOXY-, SULFATE (1:1) (SALT)
CAS number
25389-98-4
Functional Class
Veterinary Drug
ANTIMICROBIAL_AGENT

Evaluations

Evaluation year: 2003

ADI:
0–60 μg/kg bw

Comments:
The Committee noted that the current ADI for neomycin of 0–60 μg/kg bw (3.6 mg per person) is based on a safety factor of 100 & a NOEL of 6 mg/kg bw/d for ototoxicity in a 90-day study in guinea-pigs. This safety factor comprises a 10-fold interspecies extrapolation factor & interindividual variation factors. Deafness has been reported in people with the A1555G mutation given therapeutic doses of aminoglycosides. The recommended oral therapeutic dose of neomycin for adults is about 12, 000 mg/p/d, which is 3000 times greater than the current ADI. The Committee concluded that there was no need to alter the ADI of neomycin to account for the possible susceptibility of the subpopulation with the A1555G mutation or to account for the microbiological properties of neomycin.
MRL Comment:
MRLs (expressed as parent drug): Liver (cattle): 0.5 mg/kg; Kidney (cattle): 10 mg/kg; Milk (cattle): 1.5 mg/kg. The MRLs of 0.5 mg/kg for cattle muscle and fat and MRLs for tissues of other species recommended at the forty-seventh meeting were maintained.
MRL Code:
MRL
Intake:
TMDI of 3.6 mg/p/d (83% of ADI)
Meeting:
60
Report: 
TRS 918-JECFA 60/5
Tox Monograph: 
FAS 51-JECFA 60/3
Residues: 
FNP 41/15-JECFA 60/53

Toxicological study

Pivotal Study:
90-day guinea pig study (Brummett et al., 1985): Guinea-pigs (50/sex/group) were orally administered neomycin B sulfate at 0, 1, 5, or 10 mg/kg bw/day for 90 days. Two positive control groups (20/sex/group) received 10 or 100 mg/kg bw/day dose s.c. for 90 and 34 days, respectively. Parameters evaluated included clinical signs, body weight, auditory function test (Preyer pinna reflex), gross necropsy, and histopathology (including cochleae to score the loss of hair cells from the organ of Corti). The NOEL for orally administered neomycin in this study was 10 mg/kg bw/day (equivalent to 6 mg/neomycin/kg bw/day).
Animal Specie:
Guinea pig
Effect:
Ototoxicity
NOEL:
6 mg/kg bw/d
Point of departure:
6 mg/kg bw/d
Previous Years:
2002, TRS 911-JECFA 58/32, FNP 41/12-JECFA 52/91 (1999), FAS 38-JECFA 47/79 (1996). 0-0.06 mg/kg bw (1996). THE COMMITTEE MAINTAINED THE MRLs RECOMMENDED AT ITS FIFTY-SECOND MEETING (1999) AND DECIDED TO RECONSIDER THEM AT A SUBSEQUENT MEETING, WHEN IT WO
2002, TRS 911-JECFA 58/32, FNP 41/12-JECFA 52/91 (1999), FAS 38-JECFA 47/79 (1996). 0-0.06 mg/kg bw (1996). THE COMMITTEE MAINTAINED THE MRLs RECOMMENDED AT ITS FIFTY-SECOND MEETING (1999) AND DECIDED TO RECONSIDER THEM AT A SUBSEQUENT MEETING, WHEN IT WO