ENROFLOXACIN

Overview

Chemical Names
1-CYCLOPROPYL-7-(4-ETHYL-1-PIPERAZINYL)-6-FLUORO-1,4-DIHYDRO-4-OXO-3-QUINOLINE CARBOXYLIC ACID
CAS number
93106-60-6
Functional Class
Veterinary Drug
ANTIMICROBIAL_AGENT

Evaluations

Evaluation year: 1998

ADI:
0-0.002 mg/kg bw

Comments:
The Committee noted that the antimicrobial activity of ciprofloxacin against human intestinal flora was four times greater than that of enrofloxacin and that consumers may be exposed to residues of ciprofloxacin in some species of food-producing animals. The Committee considered that the fourfold greater microbiological activity of ciprofloxacin should be taken into account in recommending MRLs for this metabolite. The present Committee concluded that the microbiological effects in vitro were the most sensitive end-point on which to establish an ADI. Therefore, an ADI of 0-2 µg/kg bw was established based on the antimicrobial activity of enrofloxacin against 10 strains of the most sensitive genus isolated from the human gut. The ADI was calculated as follows: ADI (µg/kg bw) = (0.125 µg/g (MIC50) x 220 g (mass of fecal contents))/(0.2 (fractional bioavailability) x 1 (safety factor) x 60 kg (mass adult human)) = 2.3 µg/kg bw. The Committee noted that this ADI provides an adequate margin of safety in relation to the NOEL of 1.2 mg/kg bw/d for testicular toxicity in dogs described in the report of the 43rd Committee.
MRL Comment:
The evaluation of residues was postponed due to the late submission of data.
MRL Code:
O
Intake:
Not calculated
Meeting:
48
Report: 
TRS 879-JECFA 48/31
Tox Monograph: 
FAS 39-JECFA 48/47
Residues: 
FNP 41/7-JECFA 43/31

Toxicological study

Pivotal Study:
Microbiological study on gut flora in vitro (Pridmore, 1996a): The MIC50 of ciprofloxacin was determined against 100 bacterial strains of human intestinal origin (10 isolates of each of 10 genera) at a single inoculum level (107 cfu/ml). The isolates were obtained from clinical cases before the initiation of antibiotic therapy. The spectrum of bacteria included gram-positive and gram-negative organisms and facultative, moderate, and stringent anaerobes. This spectrum was considered to be representative of the typical overall human gut flora with respect to oxygen tolerance and taxonomy. The study was conducted in accordance with the principles of GLP.
Animal Specie:
Human gut flora
Effect:
Growth inhibition
Point of departure:
0.125 µg/g (MIC50)
Previous Years:
1994, TRS 855-JECFA 43/17, FNP 41/7-JECFA 43/31, FAS 34-JECFA 43/61. 0-0.0006 (TEMPORARY) (NO MRLs RECOMMENDED). TE. O
1994, TRS 855-JECFA 43/17, FNP 41/7-JECFA 43/31, FAS 34-JECFA 43/61. 0-0.0006 (TEMPORARY) (NO MRLs RECOMMENDED). TE. O